NIH_SPENDING_CATS: Biotechnology;Cancer;Gene Therapy;Genetics;Hematology;Immunotherapy;Lymphatic Research;Lymphoma;Rare Diseases

ORG_CITY: LA JOLLA

ORG_NAME: LA JOLLA INSTITUTE FOR IMMUNOLOGY

ORG_STATE: CA

PHR: Project Narrative A recent exciting development in cancer therapy involves using a patient’s own immune system to attack the cancer. The attack is accomplished by “killer CD8” T-cells that enter and destroy the malignant cells. To mount an effective attack, killer T cells need to be present in sufficient quantities and be able to renew themselves, and pathways that prevent their function need to be blocked. Some years ago, we discovered that “TET” proteins modify DNA; more recently, we showed that reducing TET protein function in T cells improves anti-cancer responses. Here we will study mouse and human T cells that infiltrate tumors to investigate how this happens, in a project very relevant to cancer immunotherapy.

PI_NAMEs: RAO, ANJANA  (contact)

PROJECT_TERMS: Alleles;alpha ketoglutarate;anti-cancer;anti-PD-1;anti-PD-L1;Antibodies;Antigens;Antitumor Response;Biological Process;Blocking Antibodies;cancer cell;cancer immunotherapy;cancer infiltrating T cells;Cancer Patient;cancer therapy;CAR T cell therapy;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Differentiation process;Cell Lineage;Cell Physiology;Cell Proliferation;Cell Surface Receptors;cell type;Cells;chimeric antigen receptor;chimeric antigen receptor T cells;Chronic;chronic infection;Chronic Lymphocytic Leukemia;Clinic;CTLA4 gene;cytokine;Cytotoxic T-Lymphocytes;Data;demethylation;Development;Dioxygenases;Disease remission;DNA;Effectiveness;Enzymes;exhaust;exhaustion;Exhibits;Exposure to;FOXP3 gene;Functional disorder;Genetic Transcription;genome-wide;Goals;Hematologic Neoplasms;Human;human model;Immune;immune checkpoint blockade;Immune response;Immune system;Immunosuppression;Impairment;improved;Infiltration;inhibitor;innovation;Iron;Ligands;loss of function;Malignant Neoplasms;Memory;methyl group;Molecular;mouse model;Mus;Mutation;Myeloid Cells;Myeloid-derived suppressor cells;Oxidases;Oxidoreductase;Oxygen;Paper;Pathway interactions;patient subsets;Patients;PD-1/PD-L1;Peptides;Phenotype;Population;prevent;Production;programmed cell death ligand 1;programmed cell death protein 1;Proliferating;protein function;Protein translocation;receptor;Regulatory T-Lymphocyte;Rejuvenation;response;restraint;Role;Signal Pathway;Signal Transduction;Solid Neoplasm;Specific qualifier value;stem;success;T cell infiltration;T-Lymphocyte;TCF Transcription Factor;Testing;Time;Transplantation;tumor;Tumor Antigens;Tumor Escape;tumor microenvironment;Tumor Promotion;Tumor-associated macrophages;Up-Regulation;Virus Diseases

PROJECT_TITLE: Exploring the potential of TET inhibition in cancer immunotherapy

STUDY_SECTION: TTT

STUDY_SECTION_NAME: Transplantation, Tolerance, and Tumor Immunology Study Section[TTT]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Genetics;Immunotherapy;Neuroblastoma;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: MEMPHIS

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: We have discovered that MYCN amplification and ATRX-mutations are synthetic lethal in neuroblastoma (NB). In this project, we will suppress ATRX pathway function in MYCN amplified NB and mimic key aspects of MYCN amplification in ATRX-mutant tumors. Discoveries from this study will be directly translated into clinical trials in children with NB at St. Jude.

PI_NAMEs: DYER, MICHAEL A (contact)

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: Acceleration;Affect;Age;Antibodies;antibody-dependent cell cytotoxicity;ATRX gene;Binding;Biogenesis;Biology;Cephalic;chemotherapy;Child;Childhood Solid Neoplasm;Clinical Trials;clinically relevant;Complex;Cyclophosphamide;cytokine;Data;Databases;Defect;design;Diagnosis;disorder risk;DNA;DNA biosynthesis;DNA Damage;DNA Polymerase I;DNA Repair;Dose;Drug Kinetics;drug sensitivity;efficacy testing;epigenomics;Evaluation;experience;G-Quartets;Generations;Genomics;Goals;Government;Growth;Health;high risk;Histones;Human;Human Cell Line;Immunotherapy;improved;improved outcome;in vivo;induced pluripotent stem cell;inhibitor;Interleukin-15;Interleukin-2;Malignant Neoplasms;Mediating;Metabolic;mitochondrial dysfunction;Molecular;Molecular Chaperones;Molecular Diagnostic Testing;molecular targeted therapies;mouse model;multidisciplinary;mutant;Mutation;MYCN gene;Natural Killer Cells;neoplastic cell;Neuroblastoma;neuroblastoma cell;novel therapeutic intervention;Oncogene Activation;Oncogenes;Outcome;Pathway interactions;Patient-Focused Outcomes;Patients;Pediatric Neoplasm;Persons;Phase I/II Clinical Trial;Play;Positioning Attribute;Preclinical Testing;prevent;Process;Prognosis;Publishing;Reactive Oxygen Species;Recurrence;Reporting;Research;Research Project Grants;Research Proposals;response;Ribosomes;RNA;Role;Saint Jude Children's Research Hospital;Schedule;Series;Solid Neoplasm;Standardization;Stress;Structure;Testing;Therapeutic;Topotecan;Toxic effect;Translating;Translational Research;tumor;tumor growth;tumor microenvironment;Tumor Suppressor Genes

PROJECT_TITLE: Novel Therapeutic Approaches for the Treatment of Neuroblastoma

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


ED_INST_TYPE: SCHOOLS OF MEDICINE

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Cervical Cancer;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Sexually Transmitted Infections;Social Determinants of Health;Women's Health Research

ORG_CITY: MINNEAPOLIS

ORG_DEPT: FAMILY MEDICINE

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE The proposed study will evaluate whether offering Somali women the opportunity to collect their own samples for HPV testing in primary care clinics is an effective strategy for increasing cervical cancer screening participation. Identifying effective and sustainable implementation strategies for HPV self-sampling in primary care could reduce disparities in cervical cancer screening among Somali patients. Findings may be transferable to other immigrant and minority groups facing similar disparities.

PI_NAMEs: PRATT, REBEKAH J. (contact);WINER, RACHEL L.

PROGRAM_OFFICER_NAME: CHOLLETTE, VERONICA

PROJECT_TERMS: acceptability and feasibility;Address;Administrator;aged;Appointment;Area;Awareness;Cervical;Cervical Cancer Screening;Clinic;Communities;Community Health Aides;Consolidated Framework for Implementation Research;design;Development;Diagnosis;Disparity;disparity reduction;effectiveness evaluation;effectiveness/implementation design;effectiveness/implementation hybrid;Female;Focus Groups;Guidelines;Health Care Costs;health disparity;health literacy;Health Personnel;Home;HPV screening;HPV-High Risk;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;Hybrids;Immigrant;implementation evaluation;implementation science;implementation strategy;Incidence;informant;Insurance Coverage;Intervention;intervention refinement;Interview;Koreans;Latino;Lesion;Male Circumcision;Malignant neoplasm of cervix uteri;Medical;Methods;Minority Groups;Modality;mortality;novel strategies;Nurses;Pap smear;patient oriented;patient population;Patients;Physicians;Population;Positioning Attribute;post implementation;post intervention;premalignant;prevent;Prevention;Preventive healthcare;Primary Care;primary care clinic;primary care setting;Process;Provider;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;Religious Belief;Research;Sampling;screening;screening disparities;screening participation;Self Efficacy;skills;social cognitive theory;System;system-level barriers;Testing;Time;treatment as usual;United States Preventative Services Task Force;uptake;Woman;Work

PROJECT_TITLE: Reducing cervical cancer screening disparities in Somali immigrant women through a primary care based HPV self-sampling intervention

STUDY_SECTION: DIRH

STUDY_SECTION_NAME: Dissemination and Implementation Research in Health Study Section[DIRH]


ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative: In this grant application, we propose to study the biological functions of transcription coactivator in advanced and treatment-refractory prostate cancer. As such, the studies proposed here will lead to the identification of novel signaling components that facilitate transcription addiction and will offer novel therapies in treating prostate cancer.

PI_NAMEs: ASANGANI, IRFAN AHMED (contact)

PROGRAM_OFFICER_NAME: LIU, ZHIHUI

PROJECT_TERMS: abiraterone;addiction;Address;advanced prostate cancer;Androgen Antagonists;androgen independent prostate cancer;Androgen Receptor;Androgens;Anti-androgen Therapy;anti-cancer research;Applications Grants;Attenuated;Biological Process;cell growth;Cell Line;Cells;Cessation of life;ChIP-seq;Chromatin;Clinical;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;CRISPR/Cas technology;Data;Death Rate;Development;Disease;Disease Progression;Disease Resistance;Drug resistance;Engineering;Enhancers;enzalutamide;Event;Foundations;Generations;Genes;Genetic;Genetic Enhancer Element;Genetic Transcription;Goals;Growth;improved;in vivo Model;ineffective therapies;inhibitor;knock-down;Knock-in;Knowledge;Ligands;Link;Malignant neoplasm of prostate;Mediating;Mediator;Metastatic Prostate Cancer;Methods;Molecular;Morbidity - disease rate;mortality;Mus;mutant;novel;novel strategies;novel therapeutics;Nuclear Receptors;Oncogenic;Oral;Outcome;patient derived xenograft model;patient population;Patients;pharmacokinetics and pharmacodynamics;pharmacologic;Phase;Phenotype;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Play;Population;potential biomarker;Prognostic Marker;programs;Prostate;prostate cancer cell;prostate cancer model;Receptor Signaling;Refractory;Refractory Disease;Research Design;Resistance;Resistance development;RNA Polymerase II;Role;Sampling;Signal Pathway;Signal Transduction;Site-Directed Mutagenesis;small molecule inhibitor;Solid;standard of care;success;System;Testing;therapeutic target;therapy resistant;Transcription Coactivator;transcription factor;Transcriptional Regulation;transcriptome;transcriptome sequencing;tumor;United States

PROJECT_TITLE: Role of MED1 in the AR-dependent transcription in advanced prostate cancer

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


NIH_SPENDING_CATS: Biomedical Imaging;Cancer;Chronic Obstructive Pulmonary Disease;Clinical Research;Health Services;Lung;Lung Cancer;Prevention

ORG_CITY: GAINESVILLE

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Public Health Relevance Currently, there is little knowledge regarding a possible threshold where the benefits of finding early-stage lung cancer no longer outweigh the risk of dying due to a competing cause. Our proposed study has direct value for advancing public health by examining real-world, timely data on the outcomes of LCS.

PI_NAMEs: BRAITHWAITE, DEJANA K (contact);GOULD, MICHAEL K;SILVESTRI, GERARD A

PROGRAM_OFFICER_NAME: MARCUS, PAMELA M

PROJECT_TERMS: Adult;Age;American Cancer Society;Assessment tool;Attention;Cancer Etiology;Cancer Intervention;Cancer Patient;cancer surgery;Cessation of life;Chronic;Chronic Obstructive Pulmonary Disease;clinical practice;Clinical Trials;comorbidity;compare effectiveness;Data;data integration;data standards;Decision Making;Diagnosis;Diagnostic Procedure;Disease;Early Diagnosis;early screening;Elderly;Electronic Health Record;Eligibility Determination;Ethnic Origin;former smoker;Funding;Geography;Goals;Health;high risk;Impairment;improved;Infrastructure;Intervention;Knowledge;Life Expectancy;Link;low dose computed tomography;Lung;lung cancer screening;Malignant neoplasm of lung;meetings;member;Modeling;models and simulation;Morbidity - disease rate;multiple chronic conditions;Observational Study;Outcome;Participant;patient oriented;patient population;Patients;personalized screening;Persons;Policies;Population;Procedures;Prospective cohort;Provider;Public Health;public health relevance;Pulmonary Emphysema;pulmonary function;Race;randomized, clinical trials;Recommendation;repository;Retrospective cohort;Risk;Risk Factors;routine screening;screening;screening guidelines;simulation;Smoker;Smoking History;Socioeconomic Status;Spottings;Therapeutic procedure;Thoracic Radiography;Time;Uncertainty;Work

PROJECT_TITLE: Personalized screening for lung cancer: the importance of co-existing chronic conditions to clinical practice and policy

STUDY_SECTION: HSOD

STUDY_SECTION_NAME: Health Services Organization and Delivery Study Section[HSOD]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_CITY: DAVIS

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE The proposed studies are aimed at understanding inter-organelle communication between lysosomes and mitochondria in mammalian cells, and how this communication contributes to cell viability and disease state. The successful completion of the studies could shed light on the cellular and molecular mechanisms underlying some of the genetic lysosomal storage diseases, and could provide an avenue for the development of novel anti-cancer drugs.

PI_NAMEs: CARRAWAY, KERMIT L (contact)

PROGRAM_OFFICER_NAME: LUO, RUIBAI

PROJECT_TERMS: Amiloride;amphiphilicity;Apoptosis;Apoptotic;Autophagocytosis;Biochemical;Biological;bis(monoacylglyceryl)phosphate;blood pressure control;Breast Cancer Cell;cancer cell;cancer recurrence;cancer stem cell;Caspase;Cathepsins;Cell Cycle;Cell Death;Cell Death Induction;Cell Death Process;Cell Differentiation process;Cell membrane;Cell Membrane Permeability;Cell model;Cell Survival;cell transformation;cell type;Cells;Ceramides;Cessation of life;Clinical;Communication;Cytosol;cytotoxic;cytotoxicity;Development;Disease;Disease Management;Diuretics;DNA Sequence Alteration;Drug Modelings;Drug resistance;Enzymes;ERBB2 gene;Event;Failure;Future;Genes;Genetic;Goals;improved;Induction of Apoptosis;insight;knock-down;Lactosylceramides;Lead;lipid metabolism;lipidomics;Lipids;Lysophosphatidylcholines;Lysosomal Storage Diseases;Lysosomes;Malignant - descriptor;Mammalian Cell;Mammary Neoplasms;Mediating;Membrane;Membrane Lipids;Metabolism;metabolomics;metaplastic cell transformation;Mitochondria;Modeling;Molecular;molecular modeling;Molecular Target;Morphology;Necrosis;neoplastic cell;Normal Cell;novel;novel anticancer drug;novel strategies;novel therapeutics;Organelles;overexpression;oxidation;Pathway interactions;Patient-Focused Outcomes;Peptide Hydrolases;Permeability;peroxidation;Pharmaceutical Preparations;Phenotype;Potassium;Production;Publishing;Reactive Oxygen Species;Recurrent tumor;Reporting;Resistance;response;Rupture;Second Messenger Systems;Secondary to;Signal Transduction;Sphingolipidoses;Sphingomyelins;stem cell population;stem cells;Supplementation;targeted treatment;Testing;Therapeutic;Therapeutic Agents;therapy resistant;Tissues;tool;tumor;Tumor Subtype

PROJECT_TITLE: Lysosomal-mitochondrial signaling in non-apoptotic cancer cell death

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-H(55)R]


ADMINISTERING_IC: GM

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Attention Deficit Hyperactivity Disorder (ADHD);Autism;Behavioral and Social Science;Brain Disorders;Clinical Research;Disability Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric

ORG_CITY: WELLINGTON

ORG_NAME: OBJECTIVE ED, INC.

PHR: 1 EXECUTIVE SUMMARY (1 page) Summary: Our Phase I prototype, College Readiness Stories (CRS) will be based on our innovative process that captures the knowledge and best practices from research scientists, practicing counselors, and successful adults with the disability and encodes their experience into a human-computer interaction, known as an Accessible Interactive Fiction (AIF) story. We developed this process as part of two NIDILRR SBIR projects; one that enables teens with Autism Spectrum Disorder (ASD) to build workplace readiness skills, and one that enables teens with vision impairments (VI) to build skills for the transition to independent adult living. Our Phase I project will answer two Specific Question:  § To what extent do college bound students with ADHD or ASD students find an AIF story  game to be a usable and engaging system to practice College Readiness executive  functioning skills?  § To what extent do non-experts find the Training Guide and Skill Charts useful for helping  college bound students with these disabilities improve these skills? These questions will be answered through four Specific Aims (SA). In SA-1, we define the specifications for the prototype AIF story game. In SA-2, create the prototype AIF story game. In SA- 3, create the Training Guide and Skill Charts. In SA-4, we assess the prototype’s usability and engagement by recruiting CBASD students and their parents to use the AIF story game and then measure the student’s rating of the story’s usability and engagement, and their parents rating of the usefulness of the Training Guide and Skill Charts. Progress: We have had numerous meetings between our development staff and the Expert team (research scientists and teachers) to identify the specific executive functioning skills that will be practiced in the AIF story, and to create the outline of the story and of each chapter in the story. We have not encountered any administrative or technical challenges yet; our primary concern is the commercial challenges that lay ahead. There are many several go-to-market alternatives; we need to determine which is the most appropriate. Team: Luke Voelk, Chief Technical Officer, is a cofounder of our company, and was entrepreneur lead in an NSF iCorp program for our other product, BuddyBooks. Luke will be the iCorp C-level Corporate Officer, as he has a strong background in customer discovery and product development. August Voelk, Product Manager, will be our Technical Lead. August has managed five AIF projects for students with disabilities, including the two mentioned above, from product definition to customer pilots. Our Industry Expert will be Mark Ventre, one of the investors in our company, and the former COO of a Special Education company that was strategically acquired. The three team members have confirmed that they are committed to the time requirements of the program. 2 I-Corps Team and Project Plan (5 pages) 1. I-Corps Team Appropriate Team Members & Appropriate Background Our iCorps Team combines the expertise of one of our three founders (CLO), our company’s product manager (TL), and an industry expert (IE) who has significant experience in bringing technology products to market. Luke Voelk (CLO) is Chief Technical Officer and cofounder of ObjectiveEd. Luke was the Entrepreneurial Lead in an NSF iCorps program for our BuddyBooks product, that uses AI to help students with dyslexia improve their reading skills. He is well-versed in use of a Business Model Canvas and has decision-making authority within the company to implement changes in direction regarding the overall commercialization strategy for the project. He implemented a pivot in the NSF project. At ObjectiveEd, Luke architected and created the technology infrastructure for the NSF-SBIR funded project, BuddyBooks. Prior to BuddyBooks at ObjectiveEd, he led the development team to bring to market over 20 skill-building apps for students with vision impairments (VI). The development staff, and the Product Manager, report to Luke. Prior to eSped, Luke was Director of Engineering at eSped, an EdTech company in the Special Ed market. Luke has a B.S. in Computer Science and Physics from Wesleyan University. August Voelk (TL) is the Product Manager for the AIF projects and has been with ObjectiveEd for 3 years. August was the Technical Lead for the NIDILRR IMPACT Program, a mini-bootcamp that helped our company understand the pain points and stakeholders AIF stories created for students with vision impairments. August coordinates the development and support teams to ensure the delivery of valuable and innovative new products, trains teachers and specialists in the use of our products, conduct seminars at key conferences and conducts in depth market research to develop new product opportunities. He graduated Franklin and Marshall College with a BA in Business and Economics. Luke and August have worked together at ObjectiveEd for 3 years. In addition to bringing the 20 skill- building VI games to market, they launched the two NIDILRR AIF story games to Special Ed departments in public schools. They launched BuddyBooks into both the public-school Special Ed market and the homeschool market (as a consumer product). While Luke (CLO) and August (TL) are both visionaries on product direction, Luke’s strengths include knowing how to translate customer dreams into deliverable products. August’s strengths are ensuring the products achieve the specific requirements and delight the customer. One example of a conflict between Luke and August is our product launch into the homeschool market for BuddyBooks. Luke’s analysis from NSF iCorps process led us to the homeschool market, while August perceived it as too distracting from the public-school market. Instead of Luke simply forcing the company to pursue the homeschool market, he presented the business case and convinced the other two founders, the board, and the other programmers that this was the proper path. Mark Ventre will be our team’s Industry Expert. Mark was the Chief Operating Officer for eSped, a company that provided compliance tracking and state/federal reporting for Special Education Departments. eSped provided services to over 1,000 school districts and managed reporting for 500,000 3 students and was the largest vendor in several states. eSped was strategically acquired by Frontline Education in 2016. Mark managed the company growth from startup to acquisition. Mark participated in the seed funding round for ObjectiveEd. Mark has reviewed the iCorps documents in the FOA and has availability consistent with the program timeframe. Deep commitment to the time-intensive requirements All team members are aware of 25 hours/week time commitment, and as a company, we are aware of the impact of the time commitment from our experience with NSF iCorps and NIDILRR bootcamp. In the two prior courses (NSF, NIDILRR), our understanding of the market evolved from the beginning of the course to its completion. We realized how we missed identifying all stakeholders, which exposed additional distribution channels, partnerships and revenue opportunities. We discovered the importance of certain factors – like acquiring proof of efficacy from the Dept. of Education, that opened additional grant funding for school districts to purchase our product. We were slightly skeptical of the business model canvas, when we started the NSF iCorp; we felt our prior Special Ed market experience was sufficient. We became advocates for this approach after seeing how effective it was for our company. We know the iCorps process will result in a deeper understanding of our market, which is needed for a successful Phase II proposal, and of course, a viable business. We are confident that if the Business Model Canvas identifies that we need to pivot, we’ll pivot. This administrative supplement will allow us to do sufficient customer investigation so that our research and development efforts are focused where the need is greatest. That ensures more college-bound students will be helped, and the company will achieve profitability sooner. During the NSF iCorps process for BuddyBooks, we acquired far more than the 100 required customer interactions. Not only did we have many Zoom conversations in the first week, but over the next two months, we attended 4 conferences and conventions to talk, face-to-face, to dozens of different types of stakeholders (competitors, parents, students, conference organizers, distribution partners, book publishers, teachers, tutors, principals, etc.). We understand the value of in-person customer discovery. 2. Potential Commercial Impact Market Opportunity College is one of life’s most important gateways to independence, success, and economic security, and college-bound students with ASD or ADHD are matriculating to college in record numbers. Despite being intellectually capable, many of these students do not make it to graduation. Only 44% of college students receive their degree – significantly less than the 60% graduation rate for all disability groups and the 67% rate for the general population. However, research consistently shows that these students need better transition planning throughout high school and continued accommodations in college, as they need to master self-regulation and executive function skills. Traditionally, counselors or teachers provide these skills. However, almost half of the public vocational rehabilitation agencies do not have sufficient staff to serve all clients properly. In some regions of the nation, there are no counselors and most Special Ed teachers are not trained to provide these skills. It is left to the parents, or other non-experts, who may not have the expertise, to prepare their student for college. Hence, there are two major problems that these college-bound students with ASD or ADHD face: § They need to master executive function skills. 4 § There are insufficient qualified counselors to provide this needed training. The Solution: College Readiness Stories (CRS) CRS is a transformative computer-mediated learning system for these students to independently improve college readiness skills. Research Scientists who study college readiness, and practicing transition counselors who provide college readiness training, have decades of experience in helping students build these skills. We capture their decades of experience and transform it into a virtual adventure story and a guide for non-experts, such as parents or Special Ed teachers. Instead of the student encountering difficult situations once they begin college, where multiple wrong decisions could result in the student getting bad grades, or dropping out of college, the student will encounter similar situations first in a safe, non-judgmental virtual story. Their “poor” decisions will result in bad outcomes, so the student can learn from their mistakes. Students will use the system independently, and won’t be as dependent on finding the excellent, but rare, counselor that will guide their transition. The system will include a Training Guide to empower the non-expert, such as a Special Ed teacher or parent, to assist the student and explain how the student can better manage difficult situations. CRS is implemented as an Accessible Interactive Fiction story game. We created our first two AIF stories as NIDILRR SBIR Phase I projects, where we realized how impactful this concept is. From testing with two different student populations, vision impairment and autism spectrum disorder, we found students enjoy learning using AIF stories, and teachers found significantly more student engagement. Market Size Based on 15% of college students having ADHD or ASD, with about 5 million students starting college each year, there are approximately 750,000 potential users (high school or starting college) who can benefit from a solution. Our conversations with these potential buyers indicate a $75 price per student per year is acceptable, yielding a total addressable market of $56 million per year. The Users The primary users for the system are the college-bound students and the non-experts who provide help to them. The Customers & Value Proposition The benefit of CRS is that more students will build executive functioning skills than the current methods (due to the counselor shortage) and that will result in more students graduating college. The customers that will benefit from this value proposition are:  § Special Ed departments, that want students to enroll in college and achieve their goal of graduating  from college. CRS will give students the confidence that they will succeed in college.  § Universities and colleges that provide accommodations and support services to ADHD and ASD  students. If students were well-prepared, through AIF stories, for the college workload, there would  be fewer students dropping out or failing out. Colleges suffer financially when students leave  without graduating.  § Community colleges that offer students 2-year degrees, as a stepping-stone to a university B.A. or  B.S. They want to prepare their students properly. Their reputation is based on the percentage of  students graduating.  § Parents who want their children to obtain a college education. 5 § College bound students, with plans to use their degree to improve their life, and not let their ASD or  ADHD limit their opportunities. § Vocational Rehab agencies, who help transition-age students (16-21 years old) prepare for post-  high school life. They are evaluated by their funders for the number of “successful” clients. § Department of Education agencies in each of the 50 states, whose mission is to improve education  outcomes for both secondary and post-secondary students. Competition In most cases, executive functioning and time/task management is not emphasized in high school for students and is not addressed as part of a Special Ed curriculum. Some colleges offer freshman orientation classes where executive function skills are discusses, and some colleges offer personalized counseling assistance as part of their accommodations for students with special needs. These services provide brochures and videos to emphasize the importance of these skills and may include role-playing. CRS’s competitive advantage is that students will experience situations in a virtual adventure, so they learn from their mistakes. We intend to conduct efficacy studies that should show an improvement in executive functioning skills, such as the Behavior Rating Inventory of Executive Function (BRIEF) test. As a company, our key differentiators are (1) we are already a trusted supplier of digital curriculum for students with a range of disabilities to the Special Ed department of school districts, and (2) we have expertise in converting peer-reviewed research findings into educational products for students. We use these research findings to build software, often scaffolding on state-of- the-art (SOTA) commercially available technology as part of the solution, which reduces the time and the costs to get a product to market. Management Team Our company has been selling digital curriculum for students with disabilities to community agencies and school districts since 2021, and we have over 150 customers, including 4 of the largest 10 school districts including the Los Angeles USD. Our company has won numerous awards for EdTech innovation, such as the 2022 Global EdTechX Startup Winner, and the EdTech 2023 Breakthrough Award. Our management team has a combined 50 years of experience in the Special Education technology market. Intellectual Property Our company protects its Intellectual Property using two strategies and will use them with this CRS. Patent-based: We have filed for several provisional patents for our innovations, and will do the same for CRS. Trade-secrets: While the OED user interfaces and functionality could be duplicated in areas that are not copyright and patent protected, there are significant trade secrets that we vigorously protect. We have accumulated significant “know-how” during research and development of our AIF products – not just how to do things, but what not to do and what does not work optimally. For example, not all students in rural and low-income communities have access to the Internet at home. We’ve built technology to accommodate for this limitation. Partnerships & Collaborations We are partners with some of the largest research centers and advocacy groups for ASD (such as the National Autism Center/May Institute), the National Disability Institute and will do the same for ADHD. We collaborate with the Council for Exceptional Children, and many state-level agencies for Special Ed Directors, such as the Texas Council of Administrators of Special Education. We have developed relationships with several state-based vocational rehabilitation agencies for services for people with 6 disabilities, such as the Massachusetts Rehabilitation Commission and the Michigan Dept of Blind Services (who is helping to connect us with the Michigan Rehabilitation Services agency). Fundraising potential Our company has raised about $1.8M seed capital through angel investors, who are familiar with the prior successes of the founding management team. We will investigate a Series A after the CRS product has completed Phase II and we want to scale marketing and sales efforts. We do not foresee additional capital requirements until then; revenue from existing products sold to school districts is sufficient to maintain company viability. 3. Project Plan Our SBIR Phase 1 project will create one AIF story for a college-bound student to demonstrate feasibility and usability. We expect the story to be ready in the February timeframe and to begin testing it as a pilot study in March/April. The Principal Investigator (PI) will perform the following assessments after the student has used the AIF story: Tool Who? Description TOOL1 PI to student Survey for students to rate items that focus on their motivation to use the AIF story, its ease of use and accessibility, and if they would recommend it to others, what they liked and didn’t like. SUS1 PI to student The System Usability Scale, where the student rates the usability of the AIF story. TOOL2 PI to parent Survey for parents to identify the usefulness of the Training Guide, suggest improvements, and if they would recommend the use of the AIF story to other parents of college-bound students. SUS2 PI to parent SUS where the parent rates the usability of the Training Guide. In Phase II, we will create at least 8 multi-chapter stories that a student would use over one to two semesters, to build and practice skills. Project/Performance Site Once these stories are complete, we will test it with sufficient students (350) to obtain Dept of Education’s What Works Clearinghouse Tier 1 proof-of-efficacy. We will conduct this with several school districts and agencies who are already customers of our other products for students with disabilities, such as Pittsburgh Public Schools. Senior/Key Personnel PI: Martin Schultz CLO: Luke Voelk TL: August Voelk IE: Mark Ventre Protection for Human Subjects We have received IRB approval for this Phase I SBIR project. Inclusion of Women, Minorities, and Individuals Across the Lifespan This is non-clinical research but will include a balanced mix of women and minorities in student testing. Vertebrate Animals and Biohazards Our research does not include either of these categories.

PI_NAMEs: SCHULTZ, MARTY  (contact)

PROGRAM_OFFICER_NAME: FAUPEL-BADGER, JESSICA

PROJECT_TERMS: 21 year old;Administrative Supplement;Administrator;Adult;Advocacy;Advocate;Age;Area;Attention deficit hyperactivity disorder;authority;autism spectrum disorder;Award;Awareness;Behavior;Binding;Biohazardous Substance;blind;Books;Businesses;Capital;career preparation;Categories;Child;Client;Collaborations;college;College Preparation;commercialization;Communities;community college;computer human interaction;computer science;Computer software;Computers;Conflict (Psychology);consumer product;cost;Counseling;Decision Making;Development;digital;disability;disabled students;Dreams;Drops;Dyslexia;Economics;Education;Educational Curriculum;Educational process of instructing;Educational Technology;efficacy study;empowerment;Engineering;Enrollment;Ensure;Equipment and supply inventories;Exceptional Child;executive function;experience;Face;fictional works;Funding;General Population;Goals;Graduation Rates;Grant;Growth;high school;High School Student;Home;Hour;Human Resources;human subject protection;improved;Individual;Industry;Informal Social Control;Infrastructure;innovation;Innovation Corps;Institutional Review Boards;Intellectual Property;Internet;Investigation;Knowledge;Lead;Learning;Left;Legal patent;Life;life span;Los Angeles;Low income;Market Research;Marketing;Massachusetts;matriculation;Measures;Mediating;meetings;member;Methods;Michigan;Minority;Mission;Modeling;Motivation;National Institute of General Medical Sciences;Outcome;Pain;Pamphlets;Parents;performance site;Persons;Phase;Physics;Pilot Projects;Population;Price;Principal Investigator;Process;product development;Professional counselor;programs;prototype;Qualifying;Reading;Recommendation;recruit;rehabilitation service;Rehabilitation therapy;Reporting;Research;research and development;Research Peer Review;Role playing therapy;Rural;Sales;scaffold;school district;Schools;Scientist;Security;Series;Services;skills;Small Business Innovation Research Grant;Special Education;Special needs;Specialist;Specific qualifier value;Staff Development;student participation;Students;success;Surveys;symposium;System;teacher;Teacher Professional Development;Technology;Teenagers;Testing;Texas;Time;tool;Training;Translating;Trust;tutoring;Universities;university student;usability;Vendor;Vertebrates;virtual;Visual impairment;Vocation;Vocational rehabilitation;Woman;Work;Workload

PROJECT_TITLE: iCorp program for NIGMS project: Interactive Fiction story to teach college readiness executive functioning skills to college-bound students with ASD and ADHD


NIH_SPENDING_CATS: Cancer;Clinical Research;Hematology;Lymphatic Research;Lymphoma;Orphan Drug;Precision Medicine;Rare Diseases

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Narrative  Drug resistance is the main problem to treat mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). We will develop a novel targeted therapy to treat MCL and CLL. We expect that successful completion of this project will make a significant impact on the treatments of B-cell malignancies.

PI_NAMEs: WANG, JIN  (contact);WANG, MICHAEL ;WOYACH, JENNIFER A.

PROGRAM_OFFICER_NAME: CHEN, WEIWEI

PROJECT_TERMS: Acrylamides;Active Sites;Agammaglobulinaemia tyrosine kinase;Antigen Receptors;Attenuated;B lymphoid malignancy;B-Cell Antigen Receptor;B-Cell Development;B-Lymphocytes;Binding;Biology;Boronic Acids;Calcium;Cell Line;Cells;Chemical Structure;Chemicals;Chemistry;Chronic Lymphocytic Leukemia;chronic lymphocytic leukemia cell;Clinic;Clinical;Clinical Research;commercialization;Complex;covalent bond;Cysteine;design;Development;drug development;drug discovery;Drug resistance;efficacy evaluation;efficacy testing;FDA approved;Goals;Half-Life;improved;In Vitro;in vitro activity;in vitro Assay;in vivo;Industry;inhibitor;kinase inhibitor;Laboratories;Lymphoma;Lymphoma cell;Mantle Cell Lymphoma;MDM2 gene;Methods;Modeling;molecular dynamics;molecular transporter;mouse model;Mus;mutant;Mutation;mutational status;Natural regeneration;new therapeutic target;next generation;novel;novel strategies;Ohio;Oral;Organic Synthesis;Pathway interactions;patient derived xenograft model;Patients;Permeability;Pharmaceutical Preparations;Phase II Clinical Trials;Phosphotransferases;Physicians;Plasma;preclinical efficacy;Property;Proteins;Reaction;Receptor Signaling;recruit;Refractory;Relapse;Reporting;Research;Resistance;resistance mechanism;Scientist;Side;Signal Pathway;small molecule therapeutics;Steroid Receptors;Sulfhydryl Compounds;targeted treatment;Therapeutic Agents;therapeutic evaluation;Therapeutic Intervention;Transgenic Organisms;Treatment Efficacy;Treatment outcome;Tyrosine Kinase Inhibitor;uptake;Work

PROJECT_TITLE: Reversible Covalent BTK Degraders as the Next Generation Targeted Therapy to Treat B-cell Malignancies

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

NIH_SPENDING_CATS: Breast Cancer;Cancer;Cancer Genomics;Genetics;Human Genome;Women's Health Research

ORG_CITY: ROCHESTER

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

PHR: Project Narrative The inability to successfully block metastatic spread remains a significant barrier to long-term cancer survival. A key early step in the progression to metastatic disease is an increase in cell state plasticity that allows some cancer cells to adapt to new environments and take on new migratory and invasive capabilities. This flexibility involves changes in non-permanent, but relatively stable chemical modifications to the DNA packaging material and a loss of control over which genes are expressed and by how much. Our studies will determine how such epigenetic modifications cross-talk to the transcriptional machinery to enforce cell state stability and suppress breast cancer cell invasion, providing new potential avenues for therapeutic intervention.

PI_NAMEs: VERTINO, PAULA M. (contact)

PROGRAM_OFFICER_NAME: AULT, GRACE S

PROJECT_TERMS: 3-Dimensional;Acetylation;Automobile Driving;Behavior;Binding;Biological Assay;Breast;Breast Cancer Cell;Breast Epithelial Cells;cancer cell;cancer survival;Cell Maintenance;Cells;Characteristics;chemical stability;Chemoresistance;Chromatin;Complex;Deposition;Development;Diagnosis;Disease;Distant Metastasis;DNA Packaging;DNA-Directed RNA Polymerase;Down-Regulation;Environment;epigenetic memory;Epigenetic Process;epigenetic variation;epigenome;epigenome editing;epithelial to mesenchymal transition;Epithelium;Exhibits;flexibility;Gene Expression;Genes;Genetic Transcription;genome-wide;Goals;Heterogeneity;Histone H4;histone methyltransferase;Hybrids;insight;Invaded;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Mesenchymal;Metastatic breast cancer;Methylation;Modeling;Modification;Molecular;mortality;neoplastic cell;novel;packaging material;Patients;Phenotype;Play;Polymerase;posttranscriptional;Precision Run-On Sequencing;Primary Neoplasm;Process;programs;promoter;Property;Reader;recruit;Regulation;Relaxation;Repression;Residual state;response;RNA;RNA Polymerase II;Role;Site;Small Nuclear Ribonucleoproteins;Solid Neoplasm;Source;spheroids;stem;stemness;Tail;Technology;Testing;Therapeutic Intervention;transcription factor;Transcriptional Regulation;transcriptional reprogramming;Transforming Growth Factor beta;triple-negative invasive breast carcinoma;Variant;Woman;women's diagnosis

PROJECT_TITLE: Relaxed Polymerase Pausing as a Driver of Epigenetic Plasticity and Cancer Cell Invasion

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE Loss of the RB1 tumor suppressor results in the transcription of cell death genes, but not a corresponding increase in cell death proteins. We found that the translation of these cell death mRNAs is silenced by the Pumilio complex of RNA binding protein(s). We propose to utilize a unique Auxin-inducible degron-mediated protein degradation system to dissect the detailed mechanism(s) associated with Pumilio complex regulation of pRB-regulated cell death transcripts in model human cells, Small Cell Lung Cancer (SCLC) cells and a well- defined murine SCLC model.

PI_NAMEs: MILES, WAYNE  (contact)

PROGRAM_OFFICER_NAME: SALNIKOW, KONSTANTIN

PROJECT_TERMS: Affect;Alleles;Apoptosis;Apoptotic;Auxins;Binding;Binding Proteins;BRAT gene;cancer cell;Cancer Cell Growth;Cancer Model;cancer therapy;Cell Cycle;Cell Death;cell growth;cell growth regulation;Cell Proliferation;Cells;Complex;Coupling;cytotoxic;Data;Development;E2F transcription factors;Gene Expression Regulation;gene repression;Genes;Genetic Transcription;Genetically Engineered Mouse;Genomics;Homologous Protein;Human;human disease;Human Engineering;Human Genome;human model;Individual;inducible Cre;Kinetics;Link;LoxP-flanked allele;lung cancer cell;Malignant Neoplasms;Mediating;member;Messenger RNA;Metabolic;Methods;MicroRNAs;Modeling;Mus;mutant;Necrosis;Neoplasm Metastasis;Neoplasms;novel;Pathologic;Pathway interactions;Patients;Pattern;Play;posttranscriptional;prevent;Process;Production;Proliferating;Protein Biosynthesis;protein complex;Protein Deficiency;protein degradation;Protein Family;protein function;Proteins;RB1 gene;Regulation;response;Ribosomes;RNA;RNA analysis;RNA Stability;RNA-Binding Proteins;Role;small cell lung carcinoma;Survival Rate;System;Testing;therapy design;Transcript;Transcription Coactivator;Translation Initiation;Translational Regulation;Translations;tumor;Tumor Promotion;Tumor Suppressor Proteins;tumorigenesis;uncontrolled cell growth;Work;Zinc Fingers

PROJECT_TITLE: The Translational Regulation of Pro-apoptotic Genes


NIH_SPENDING_CATS: Breast Cancer;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Orphan Drug;Rare Diseases;Women's Health Research

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: Many metastases of breast cancer may further disseminate to seed more metastases, but the pre-clinical models, the underlying mechanisms, and the potential therapeutic targets are all lacking. Herein, based on several lines of preliminary evidence, we propose to test the hypothesis that the bone microenvironment invigorates metastatic seeds for further dissemination. Specifically, we will focus on delineation of temporal course of metastatic seeding from bone to other organs, and identification of druggable pathways driving this process.

PI_NAMEs: ZHANG, XIANG  (contact)

PROGRAM_OFFICER_NAME: SNYDERWINE, ELIZABETH G

PROJECT_TERMS: Adjuvant;Affect;Automobile Driving;Bar Codes;bone;bone cell;Brain;Breast Cancer Cell;breast cancer metastasis;Breast Cancer Patient;cancer cell;cancer stem cell;Cell Line;Cessation of life;Circulation;Complement;CRISPR/Cas technology;Data;design;Destinations;Diagnosis;Distant;druggable target;Epigenetic Process;epigenomics;Evolution;fetal;genetic selection;genomic locus;Genomics;Guide RNA;high risk;inducible gene expression;innovation;insight;Investigation;Kinetics;Lesion;limb bone;Liver;Lung;Malignant Bone Neoplasm;Malignant Breast Neoplasm;Mediating;Metastatic Neoplasm to the Bone;Micrometastasis;Modeling;Mutate;Neoplasm Metastasis;novel therapeutics;Organ;Outcome;Parabiosis;Pathway interactions;patient derived xenograft model;Patients;Phenotype;Pre-Clinical Model;prevent;Prevention;Primary Neoplasm;Process;Prognosis;Property;Recurrence;Research;restraint;Site;Skeleton;stem;stemness;System;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;Time;tumor;Visceral;Work

PROJECT_TITLE: Mechanistic and therapeutic investigation of secondary metastatic seeding from breast cancer bone lesion

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


ORG_CITY: BUFFALO

ORG_NAME: ROSWELL PARK CANCER INSTITUTE CORP

PHR: Majority of the patients with aggressive prostate cancer develop resistance to therapy and the tumor metastasizes to bones and other visceral organs accounting for high morbidity and mortality. The goal of this project is to define the underlying mechanisms that promote the survival and colonization of prostate tumor cells in the bone microenvironment. Our study will uncover molecular links between mitochondrial metabolism and transcriptional regulation that enables PCa adaptation, survival and ultimately metastatic competency.

PI_NAMEs: DASGUPTA, SUBHAMOY  (contact)

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: Ablation;Accounting;Acetylation;Aconitate Hydratase;Advanced Development;advanced disease;advanced prostate cancer;Anabolism;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;Androgens;Automobile Driving;Binding;Bioenergetics;bone;Cancer Patient;cancer survival;Carbon;Castration;Cell Nucleus;Citrates;Clinical;Communication;Competence;Data;Deacetylase;Dependence;Disease;enzyme activity;Enzymes;Event;fatty acid biosynthesis;Fatty acid glycerol esters;Fatty Acids;gene repression;gene synthesis;Genes;Genetic;genetic corepressor;Genetic Transcription;Glutamine;Goals;GRIP1 gene;Growth;Homing;Hormones;Human;in vivo;Link;lipid biosynthesis;Lipids;loss of function;Lysine;Malignant neoplasm of prostate;Mediating;men;Metabolic;Metabolic stress;Metabolism;Metastatic Neoplasm to the Bone;Metastatic Prostate Cancer;mimetics;Mitochondria;mitochondrial metabolism;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;mutant;NCOA2 gene;Neoplasm Metastasis;novel;Nuclear;Nuclear Receptors;Oncogenic;Organ;Organelles;Pathogenesis;Pathway interactions;Patients;Physiological;Play;Primary Lesion;programs;promoter;Property;Prostate;prostate cancer cell;prostate cancer model;prostate cancer progression;Prostatic Neoplasms;Proteins;Recurrence;Refractory;Relapse;Repression;Resistance development;restoration;Role;Signal Transduction;Sirtuins;steroid hormone receptor;Steroid Receptors;Therapeutic;therapy resistant;Transcriptional Activation;Transcriptional Regulation;tumor;Tumor Suppressor Proteins;Visceral

PROJECT_TITLE: Mechanisms of metabolic stress-induced transcriptional regulation in prostate cancer


NIH_SPENDING_CATS: Breast Cancer;Cancer;Immunotherapy;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Women's Health Research

ORG_CITY: ANN ARBOR

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer associated with an increased proportion of cancer stem cells (CSCs). In this application, we utilize IB-DNQ, a futile redox cycling compound bioactivatable by NQO1 to generate large amounts of reactive oxygen species, an effect potentiated by SOD1 inhibition to target CSCs of TNBC. We will elucidate the mechanisms by which this pro-oxidant strategy induces apoptotic and pyroptotic cell death in CSCs, leading to enhanced host antitumor immunity. Since CSCs display resistance to conventional cancer treatments as well as to immunotherapy, this strategy has the potential to improve the outcome for women with this aggressive form of breast cancer.

PI_NAMEs: WICHA, MAX S. (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: Adjuvant;aldehyde dehydrogenases;Antioxidants;Apoptosis;Apoptotic;cancer cell;cancer stem cell;cancer therapy;CASP3 gene;catalase;Cell Death;Cell Death Induction;cell killing;cell type;Cells;Chemotherapy and/or radiation;Clinical;conventional therapy;Cytoprotection;Disease;Enzymes;Epithelium;Generations;Genetic;human model;Hydrogen Peroxide;Immune;immune checkpoint blockers;Immune Targeting;Immunocompetent;Immunodeficient Mouse;immunogenic;immunological status;Immunologics;Immunotherapy;Impairment;improved;improved outcome;In Vitro;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Membrane Potentials;Mesenchymal;Metabolic;metabolic profile;Mitochondria;mitochondrial membrane;Molecular;mouse model;Mus;Neoplasm Metastasis;neoplastic cell;novel;novel therapeutic intervention;Outcome;overexpression;oxidant stress;Oxidants;Oxidation-Reduction;oxidative damage;Oxidoreductase;Patient-Focused Outcomes;pharmacologic;Process;Production;Quinones;Reactive Oxygen Species;Recurrence;Resistance;SOD2 gene;Solid Neoplasm;stem-like cell;superoxide dismutase 1;Superoxides;Supporting Cell;synergism;Therapeutic;therapy resistant;triple-negative invasive breast carcinoma;tumor;tumor growth;Tumor Immunity;tumor microenvironment;women's outcomes;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Targeting Metabolic Vulnerabilities of Triple Negative Breast Cancer Stem Cells

STUDY_SECTION: MCTA

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics A Study Section[MCTA]


ORG_DEPT: UROLOGY

PHR: Intratumoral androgen biosynthesis is well characterized as one of the important mechanisms of castration resistant prostate cancer (CRPC). This application is aimed to determine the roles of steroid sulfatase (STS) in progression and resistance to next-generation anti-androgen therapy, and develop novel STS inhibitors to target STS activity to potentially inhibit CRPC growth and reverse treatment resistance.

PI_NAMEs: GAO, ALLEN C. (contact)

PROJECT_TERMS: abiraterone;advanced prostate cancer;Androgen Antagonists;androgen biosynthesis;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;androgenic;Androgens;Anti-androgen Therapy;Biological Availability;Cancer Patient;carcinogenesis;cell growth;Cell Line;Cells;Clinical;Clinical Treatment;CYP17A1 gene;Data;Databases;dehydroepiandrosterone;design;Down-Regulation;effective therapy;enzalutamide;Enzymes;experience;Generations;Genetic Transcription;Growth;Hydroxysteroid Dehydrogenases;improved;In Vitro;in vivo;in vivo Model;inhibitor;Intervention;intratumoral androgen;Investigation;knock-down;LNCaP;Malignant neoplasm of prostate;Mediating;men;Messenger RNA;Mutation;next generation;novel;Organic Anion Transporters;overexpression;Oxidoreductase;patient derived xenograft model;Pharmaceutical Preparations;Plasma;Play;Production;prostate cancer cell;prostate cancer progression;Resistance;Resistance development;Role;Safety;Sampling;Signal Transduction;Small Interfering RNA;small molecule inhibitor;Source;Specimen;Stanolone;Steroid biosynthesis;Steroids;Sulfatases;System;Testing;Testosterone;therapeutic target;therapy resistant;Treatment Failure;treatment response;treatment strategy;Variant;VCaP;Xenograft procedure

PROJECT_TITLE: Therapeutic targeting steroid sulfatase for advanced prostate cancer

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Genetics;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_CITY: SAN ANTONIO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: NARRATIVE We have identified a mitochondrial signaling axis centered on MnSOD-K68 which, when its normal acetylation status is altered, disrupts cell metabolism, leading to aberrant-ROS levels, and a tumor permissive phenotype (Zhu et al, 2019). Interestingly, emerging data suggests that the disruption of mitochondrial metabolism, including aberrant ROS levels, is an increasingly accepted mechanism of oncogenicity due to an enrichment of stem-like cells. Thus, it is proposed that when MnSOD-Ac exists outside of its normal physiological context, it disrupts cellular and mitochondrial metabolism and promotes lineage plasticity properties (or tumor cell stemness), leading to an oncogenic permissive and TamR phenotype, and is a potential target for new therapies.

PI_NAMEs: GIUS, DAVID  (contact)

PROGRAM_OFFICER_NAME: WILLIS, KRISTINE AMALEE

PROJECT_TERMS: Acetylation;Adjuvant Therapy;Biological Markers;Biology;Breast Cancer Cell;breast malignancies;cancer cell;Cell Physiology;Cells;Cellular Metabolic Process;Chemicals;ChIP-seq;Cisplatin;Clustered Regularly Interspaced Short Palindromic Repeats;Compensation;Data;Doxorubicin;Drug Metabolic Detoxication;Endocrine;Equilibrium;Estrogen receptor positive;Event;Exhibits;Exposure to;Fatty acid glycerol esters;Fulvestrant;Genes;high risk;hormone therapy;in vivo;knock-down;Knock-out;Lead;Link;Lysine;Malignant Breast Neoplasm;Malignant Neoplasms;mammary;Mammary Neoplasms;MCF7 cell;Measurement;Measures;Mediating;Metabolic;Metabolism;mimetics;Mitochondria;mitochondrial metabolism;Modeling;monomer;mouse model;mutant;Nature;neoplastic cell;new therapeutic target;novel;Oncogenic;Pathway interactions;patient derived xenograft model;permissiveness;Peroxidases;Phenotype;Physiological;Post-Translational Protein Processing;prevent;programs;Property;public database;Publications;Reactive Oxygen Species;Recurrence;Reporter;Resistance;response;Risk;Selective Estrogen Receptor Modulators;Signal Transduction;Sirtuins;small hairpin RNA;SOD2 gene;Stains;stem;stem cell biomarkers;stem-like cell;stemness;Subgroup;Superoxides;Systemic Therapy;T47D;Tamoxifen;targeted treatment;Techniques;Testing;therapy resistant;Time;tissue culture;Tissue Microarray;transcriptome sequencing;tumor;Tumor Promoters;tumorigenesis;tumorigenic;Woman;Work;Xenograft Model

PROJECT_TITLE: MnSOD-K68-Ac reprograms a lineage plasticity switch / stemness in ER+ breast malignancies


NIH_SPENDING_CATS: Bioengineering;Breast Cancer;Cancer;Women's Health Research

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: The majority of breast cancer deaths result from metastatic disease. Accumulated evidence indicates that breast tumor cells invade as complex, heterogeneous clusters rather than single cells and to do so they are led by cells called leader cells. How these leader cells develop to lead directed collective migration, and whether this phenomenon is necessary and sufficient to effect directed collective migration is largely unknown. This is a focus of the current proposal.

PI_NAMEs: LONGMORE, GREGORY D. (contact);PATHAK, AMIT

PROJECT_TERMS: 3-Dimensional;Adhesions;Affect;Basement membrane;Biological Process;biomechanical engineering;Biomedical Engineering;Biophysics;Blood Vessels;Breast Cancer Cell;Breast Cancer Model;Cancer Biology;Cancer Etiology;Carcinoma;cell motility;Cells;Cessation of life;chemical property;Chemicals;chemokine;Circulation;Collagen;Complex;Computer Models;Computer Simulation;Coupling;Data;Development;Disease;Environment;Event;Extracellular Matrix;Feedback;Fibroblasts;Hemidesmosomes;Heterogeneity;Human;Hypoxia;insight;Integrins;Intercellular Junctions;Invaded;Lead;live cell imaging;Lymphatic;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;mechanical properties;mechanical signal;Mechanics;mechanotransduction;Mediating;Microfluidic Microchips;Microfluidics;migration;Molecular;Motility;mouse model;Movement;Neoplasm Circulating Cells;Neoplasm Metastasis;neoplastic cell;novel;Organ;Organoids;Pathway interactions;polarized cell;preservation;Primary Neoplasm;Production;Regulation;response;Signal Transduction;single-cell RNA sequencing;Source;Stromal Cells;Stromal Neoplasm;Subgroup;Testing;transcriptome sequencing;treatment response;tumor;Tumor Cell Invasion;tumor microenvironment;tumor progression

PROJECT_TITLE: Leader cell development and function in Breast Tumor Collective Migration


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Breast Cancer;Cancer;Women's Health Research

ORG_CITY: BALTIMORE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: The inability to clinically treat cancer metastasis is responsible for the majority of patient deaths from solid tumors, including breast cancer. Cell migration is a pivotal step in the metastatic dissemination of cancerous cells from a primary tumor to distant organs in the body. We herein employ a multidisciplinary approach, which integrates state-of-the-art bioengineering and imaging tools, quantitative analysis and in vivo models, to offer a comprehensive understanding of the mechanisms driving breast cancer cell migration in physically-confined spaces and identify novel therapeutic targets to reduce breast cancer metastasis.

PI_NAMEs: KONSTANTOPOULOS, KONSTANTINOS  (contact);MARTIN, STUART S

PROJECT_TERMS: 3-Dimensional;Actins;Actomyosin;Affect;Automobile Driving;Biological Models;Biomedical Engineering;Breast Cancer Cell;Breast Cancer cell line;breast cancer metastasis;Cancer Biology;cancer cell;Cancer Patient;Cancerous;Cell Cycle;Cell membrane;cell motility;Cell Separation;Cell surface;Cell Volumes;Cells;Cellular biology;Cessation of life;Clinical;combat;Complement;Confined Spaces;Cytoplasm;Cytoskeleton;Data;Dissociation;Distant;Elements;Event;experimental study;Extracellular Matrix;Fatty acid glycerol esters;Fiber;fluid flow;Gel;Goals;Growth;Image;Imaging Device;In Vitro;in vivo;in vivo Model;Individual;innovation;Integrins;interdisciplinary approach;interstitial;Intracellular Transport;intravital microscopy;Ion Channel;Ions;Light;live cell imaging;Malignant Breast Neoplasm;mammary;mathematical model;Mediating;Metastatic breast cancer;Microfluidic Microchips;Microtubules;migration;Modeling;Molecular;Molecular Biology;Motility;mouse model;multiphoton microscopy;Mus;Myosin Type II;Neoplasm Metastasis;neoplastic cell;new therapeutic target;novel;Optics;optogenetics;Organ;Organoids;Osmosis;patient derived xenograft model;Patients;Phase;Primary Neoplasm;Regulation;Research Personnel;Role;Solid Neoplasm;Swelling;targeted treatment;Testing;therapeutic target;Tissues;tool;Transplantation;Travel;triple-negative invasive breast carcinoma;tumor;Tumor Cell Migration;tumorigenic;Water;water channel;Work;Zebrafish

PROJECT_TITLE: The interplay of ion transporters and cytoskeleton in breast cancer migration and metastasis


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Digestive Diseases;Immunotherapy;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative Most of the over 40,000 patients diagnosed with pancreatic cancer each year in this country will die from metastatic disease. Irreversible electroporation (IRE) is a non-thermal ablation technique that is currently being used clinically to treat locally advanced tumors. The goal of this research is to understand effects of IRE on the immune system and to augment these effects using immunotherapy agents to eradicate distant micrometastatic disease.

PI_NAMEs: WHITE, REBEKAH  (contact)

PROGRAM_OFFICER_NAME: HU, ZHANG-ZHI

PROJECT_TERMS: Ablation;Abscopal effect;adaptive immune response;Adjuvant;Adjuvant Therapy;advanced pancreatic cancer;Agonist;anti-tumor immune response;Antibodies;antigen-specific T cells;Biology;cancer immunotherapy;candidate identification;CD8-Positive T-Lymphocytes;Cells;Cellular Assay;checkpoint inhibition;Cicatrix;Clinical;clinical care;Clinical Trials;clinically relevant;Combined Modality Therapy;Contralateral;Country;Data;Dendritic Cells;design;Diagnosis;Disease;Distant;DNA delivery;Effector Cell;Electroporation;Fibrosis;Future;Goals;Human;Immune;immune cell infiltrate;Immune response;Immune system;Immunity;Immunocompetent;Immunocompromised Host;Immunodeficient Mouse;Immunologic Adjuvants;Immunotherapeutic agent;Immunotherapy;Implant;improved;in situ vaccine;Infiltration;Inflammation;Inflammatory;Innate Immune Response;Innate Immune System;Invaded;irradiation;Laboratories;Localized Disease;Malignant neoplasm of pancreas;Metastatic Neoplasm to the Liver;Methods;Modeling;mouse model;multidisciplinary;Mus;neoantigens;Neoplasm Metastasis;new growth;novel;Operative Surgical Procedures;Organoids;pancreatic cancer model;pancreatic cancer patients;Patient Care;patient derived xenograft model;Patient-Focused Outcomes;Patients;pre-clinical;Pre-Clinical Model;prevent;prophylactic;Proteins;Radiation therapy;reconstitution;Recurrence;Research;response;RNA;Specimen;subcutaneous;T cell response;T-Cell Activation;T-Lymphocyte;Techniques;Therapeutic;TLR7 gene;TNFRSF5 gene;Toll-like receptors;treatment response;tumor;tumor ablation;tumor growth;Tumor Immunity;tumor microenvironment;Tumor-infiltrating immune cells;voltage

PROJECT_TITLE: Combining Irreversible Electroporation with Immunotherapy for the Systemic Treatment of Pancreatic Cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-M(08)F]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Genetics;Women's Health Research

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Completion of this work will provide a detailed mechanistic understanding of how SAMHD1 non-catalytically directs CtIP function in DSB repair to maintain genome integrity and govern breast cancer treatment resistance and new insights into how SAMHD1 dysregulation leads to genomic instability and development of disease, including cancer, autoimmune disease, and viral infection. In addition, this work is expected to elucidate the significance of the SIRT1 acetylome in directing SAMHD1 in DSB repair, providing new insights into the upstream signaling events governing SAMHD1 function in DSB repair and how loss of Sirt1 results in an in vivo tumor permissive phenotype. Finally, this work will establish proof of concept for the use of VLPs with Vpx in targeting SAMHD1 as a novel therapeutic approach for sensitizing resistant breast cancer to DSB-inducing agents that may significantly improve clinical outcomes.

PI_NAMEs: KIM, BAEK ;YU, DAVID SUNG-WEN (contact)

PROGRAM_OFFICER_NAME: WEINREICH, MICHAEL DALE

PROJECT_TERMS: Acetylation;Adjuvant;Autoimmune Diseases;Binding;Biochemical;Biological;Biological Models;Breast Cancer Cell;Breast Cancer Patient;Breast Cancer therapy;Breast Cancer Treatment;Cancer Control;cancer therapy;cancer type;carcinogenesis;Cells;chemotherapy;Clinical;Complex;Crystallization;cytotoxic;Data;Deacetylation;Development;Disease;DNA;DNA Damage;DNA Double Strand Break;domain mapping;Double Strand Break Repair;Event;Excision;Exhibits;Exposure to;Genetic;genome integrity;Genomic Instability;Goals;HIV-1;homologous recombination;Human;improved;In Vitro;in vivo;inhibitor therapy;innovation;insight;Ionizing radiation;Lentivirus;Lysine;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Metabolism;Molecular Target;mouse model;Mutation;neoplastic cell;novel;novel therapeutic intervention;novel virus;nuclease;Outcome;overexpression;Pathway interactions;patient derived xenograft model;Patients;permissiveness;Phenotype;Poly(ADP-ribose) Polymerase Inhibitor;Process;Proteins;Proteomics;pseudotoxoplasmosis syndrome;radiation resistance;recombinational repair;recruit;Regulation;repaired;Resistance;response;Role;SAM Domain;Signal Transduction;Single-Stranded DNA;SIRT1 gene;Structure;targeted cancer therapy;Testing;therapy resistant;tripolyphosphate;tumor;Virus Diseases;Virus-like particle;Work

PROJECT_TITLE: Elucidating SAMHD1 in DNA Double-Strand Break Repair

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Colorectal Cancer;Digestive Diseases;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Rural Health;Social Determinants of Health;Women's Health Research

ORG_CITY: IOWA CITY

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE The 60 million rural residents of the United States have a lower rate of new cases of cancer per year compared to urban residents but have a higher rate of cancer deaths per year, partly due to the greater difficulty in accessing high-quality cancer treatment in rural areas. As rural patients are less likely to receive care in urban cancer centers with cancer specialists who treat very large numbers of cancer patients, an effective strategy used by the University of Kentucky Markey Cancer Center has been to share their expertise and resources with smaller community hospitals across Kentucky to help improve their quality of care. We propose to study the Kentucky model in order to identify and characterize its core functions (i.e., what made it effective in improving quality of care in community hospitals), adapt it to a new rural setting, and determine its value to the hospitals and impact on cancer care.

PI_NAMEs: CHARLTON, MARY E. (contact)

PROGRAM_OFFICER_NAME: WEAVER, SALLIE JAYNE

PROJECT_TERMS: Accreditation;adaptation algorithm;Address;Adopted;Adoption;American College of Surgeons;Area;Breast;breast cancer diagnosis;Breast-Conserving Surgery;cancer care;Cancer Center;Cancer Death Rates;cancer health disparity;Cancer Patient;cancer therapy;cancer type;Caring;Colon Carcinoma;Colorectal;Colorectal Cancer;Community Hospitals;Consolidated Framework for Implementation Research;cost;Data;Data Collection;data registry;Death Rate;Diagnosis;Diffusion;disparity reduction;draining lymph node;Effectiveness;evidence base;Familiarity;Goals;Guidelines;health difference;Health system;Healthcare;Home;hospital care;Hospitals;implementation determinants;implementation outcomes;implementation process;implementation science;improved;Incidence;Infrastructure;Intervention;Intervention Trial;Interview;Iowa;Kentucky;Logistics;Malignant Breast Neoplasm;Malignant Neoplasms;Measures;Methods;Modeling;Monitor;mortality;multidisciplinary;Needs Assessment;neoplasm registry;network models;novel;Outcome;Patients;Pattern;Performance;Physicians;Population;post intervention;preference;preservation;Proctor framework;programs;psychosocial;Qualifying;Quality of Care;Radiation therapy;Readiness;Research;Resected;Resource Sharing;Resources;Risk;Rural;rural area;rural cancer care;rural disparities;rural dwellers;Rural Hospitals;rural patients;Rural Population;rural setting;Services;Social support;Specialist;Specific qualifier value;Structure;survival outcome;survivorship;Testing;theories;Time;tool;Transportation;treatment guidelines;treatment planning;United States;Universities;Urban Population;Woman;Work

PROJECT_TITLE: Effectiveness and implementation of a health system intervention to improve quality of cancer care for rural, underserved patients


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Digestive Diseases;Gene Therapy;Genetics;Immunotherapy;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: PUBLIC HEALTH RELEVANCE Pancreatic cancer is a leading cause of cancer mortality with few effective therapies. This project will develop a novel immunotherapy that we show has pronounced therapeutic activity in preclinical animal models. We will uncover the mechanistic basis for the observed antitumor effects and create a novel immune therapy designed to change the standard of care for pancreatic cancer patient treatment.

PI_NAMEs: STROMNES, INGUNN MARGARETE (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: Adoptive Cell Transfers;Advanced Malignant Neoplasm;Affinity;Animal Model;Animals;Antigen Presentation;antigen-specific T cells;Antigens;antitumor effect;Antitumor Response;base editor;Biological Assay;Blood Vessels;Bypass;Cancer Etiology;Cancer Model;Cancer Patient;Carcinoma;Cell Death;Cell Physiology;Cell Therapy;cell type;Cells;cellular engineering;Characteristics;chimeric antigen receptor;Chronic;Clinical;Coculture Techniques;comparative efficacy;CRISPR/Cas technology;cytokine;Cytometry;Cytotoxic T-Lymphocytes;Data;Defect;Diagnosis;Disease;effective therapy;Endothelial Cells;engineered T cells;exhaustion;Extracellular Matrix;Fibroblasts;gene editing technology;Gene Modified;Genetic Engineering;Human;human disease;Immune;immune checkpoint blockade;Immune Evasion;immunoregulation;Immunotherapy;In Vitro;in vivo;innovation;Knock-in Mouse;Knowledge;Learning;Legal patent;Macrophage;Malignant neoplasm of lung;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Mesenchymal;mesothelin;Modeling;mortality;mouse model;Mus;mutant;Myelogenous;Myeloid Cells;Neoplasm Metastasis;neoplastic cell;Normal Cell;novel;overexpression;pancreatic cancer patients;Pancreatic Ductal Adenocarcinoma;pancreatic neoplasm;Patients;Pharmaceutical Preparations;Phase I Clinical Trials;pre-clinical;Preclinical Testing;Predisposition;Primary Neoplasm;Production;progenitor;programmed cell death protein 1;programs;Proteins;public health relevance;Receptor Signaling;Regulatory T-Lymphocyte;Reporter;Resistance;response;Role;Safety;safety testing;screening;Signal Transduction;single-cell RNA sequencing;Solid Neoplasm;Specificity;standard of care;stem;T cell differentiation;T cell infiltration;T cell response;T cell therapy;T-Cell Receptor;T-Lymphocyte;targeted treatment;Testing;Therapeutic;Therapeutic Effect;therapy design;therapy resistant;tool;Toxic effect;Toxicity Tests;transcription factor;Translating;Treatment Efficacy;tumor;Tumor Antigens;Tumor Immunity;tumor microenvironment;tumor xenograft;vector;Xenograft Model

PROJECT_TITLE: Enhancing engineered T cell therapeutic efficacy for the treatment of pancreatic ductal adenocarcinoma


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Digestive Diseases;Esophageal Cancer;Genetics;Human Genome;Infectious Diseases;Microbiome;Prevention;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE Deaths from esophageal adenocarcinoma continue to rise, yet factors driving this trend remain poorly understood. We hope to demonstrate that the inter-relationship between gastro-esophageal reflux bile acid composition, Notch signaling activity, and esophageal bacterial composition is key to driving esophageal neoplasia. This knowledge can in turn be translated to future efforts to modify these factors to prevent esophageal cancer.

PI_NAMEs: ABRAMS, JULIAN  (contact)

PROGRAM_OFFICER_NAME: GEORGE, CHRISTINA DAWN

PROJECT_TERMS: Acceleration;Acids;Antibiotics;Area;aspirate;Automobile Driving;Bacteria;Barrett Esophagus;Bile Acids;carcinogenesis;carcinogenicity;Case/Control Studies;Cell Differentiation process;Cessation of life;Chronic;Clinical;cohort;Collaborations;Colon;Colon Carcinoma;Data;Deoxycholic Acid;Development;Dysplasia;Enrollment;Enterobacteriaceae;Epithelium;Esophageal Adenocarcinoma;Esophageal Neoplasms;Esophageal Tissue;Esophagus;experimental study;Feedback;Future;gastric microbiome;Gastroesophageal reflux disease;gastrointestinal epithelium;Goals;Goblet Cells;gut microbiome;Helicobacter Infections;Helicobacter pylori;High grade dysplasia;high risk;Homeostasis;Incidence;infection rate;Inflammation;Intervention;Intestines;Knowledge;Lesion;Logistic Regressions;Malignant neoplasm of esophagus;Malignant Neoplasms;Microbial Biofilms;microbiome;microbiome alteration;microbiome composition;Minority;Modeling;modifiable risk;mouse model;Mucins;Mucous body substance;Mutagens;Neoplasms;NF-kappa B;notch protein;novel;Obesity;Organoids;Pathway interactions;Patients;Population;Prevalence;prevent;Probiotics;Production;Prognosis;prospective;Prospective cohort;Public Health;Research;Risk;Risk Factors;Role;Sampling;Series;Signal Transduction;Stomach;Study models;Testing;Thinness;Time;Tissue Sample;Translating;trend;Upper digestive tract structure;Work

PROJECT_TITLE: The Role of the Microbiome and Notch Signaling in Esophageal Adenocarcinoma

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE Tumor heterogeneity is a well-known property of treatment resistant, recurrent, and metastatic breast cancer. The proposed research project is relevant to public health because it will provide a genetically tractable Cancer rainbow mouse model for inducing and visualizing tumor heterogeneity in an immune intact system. The proposed studies will credential the use of a novel Crainbow mouse model that more accurately recapitulates the heterogeneity found in treatment resistant HER2+ breast cancer patients. Our proposal will significantly improve upon the translational utility of mouse models for preclinical trials and at the same time provide a reliable tool for reconstructing the molecular and cellular interactome controlling tumor heterogeneity.

PI_NAMEs: SNYDER, JOSHUA CLAIR (contact)

PROGRAM_OFFICER_NAME: WATSON, JOANNA M

PROJECT_TERMS: Animals;Bar Codes;Basic Science;Biological Models;Breast Cancer Model;Breast Cancer Patient;Carcinoma;Cells;Clinic;Clinical effectiveness;clinical predictors;Clonal Evolution;Clonality;Complex;Credentialing;Data;diagnostic assay;efficacy research;Epithelial Cells;Epithelium;ERBB2 gene;Evolution;fluorescence imaging;Future;gastrointestinal epithelium;Gene Modified;Genes;Genetic;Genetic Heterogeneity;Genetic Models;Growth;Heterogeneity;Human;human disease;Immune;Immune system;improved;Invaded;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary gland;Maps;Metastatic breast cancer;Modeling;Molecular;mouse model;multiplex diagnostics;Mus;Neoplasm Metastasis;novel;novel therapeutics;Oncogenes;Oncogenic;Outcome;Phenotype;Pre-Clinical Model;preclinical trial;premalignant;Property;Protein Isoforms;Protocols documentation;Public Health;Publishing;Recurrence;Reproducibility;Research Project Grants;Resistance;Resources;Somatic Mutation;Source;spectrograph;standard of care;Standardization;stem;Stromal Cells;System;Techniques;Testing;Therapeutic Uses;therapy resistant;Time;tool;transcriptomics;Translating;Translational Research;Treatment Efficacy;treatment response;tumor;Tumor Biology;Tumor Escape;tumor heterogeneity;tumor microenvironment;Variant;Visualization;Work

PROJECT_TITLE: Visualizing tumor heterogeneity in an immune intact and autochthonous mouse model of breast cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-N(55)R]


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Lung;Lung Cancer;Nutrition;Obesity;Prevention;Tobacco;Tobacco Smoke and Health

PHR: PROJECT NARRATIVE Despite several ground-breaking advances in the treatment of lung cancer, the overall outlook remains dismal, necessitating the urgent development of preventive therapies. We have observed that use of the anti-diabetic drug metformin is associated with improved lung cancer outcomes selectively in patients who are overweight and obese and have linked this association to metformin-induced immunological changes in both humans and mice. With a clinical trial and mouse experiments, we propose to study if the anti-cancer immune effect of metformin occurs in obese subjects who have a high risk for developing lung cancer occurs so that the drug may be used for cancer prevention.

PI_NAMEs: BARBI, JOSEPH ;REID, MARY E;YENDAMURI, SAIKRISHNA  (contact)

PROGRAM_OFFICER_NAME: SZABO, EVA

PROJECT_TERMS: Abate;Adenocarcinoma;Age;anti-cancer;Anti-diabetic Drugs;antitumor effect;Biological Response Modifiers;Biopsy;Blood;Body mass index;Bronchoalveolar Lavage;cancer diagnosis;Cancer Etiology;Cancer Model;cancer prevention;cancer risk;carcinogenesis;Cells;Chemoprevention;Chemopreventive Agent;cigarette smoking;Clinical Data;Clinical Research;Clinical Trials;Collaborations;Color;cytokine;Cytometry;Development;Diabetes Mellitus;Disease;Disease Progression;disorder risk;Division of Cancer Prevention;Environment;Enzyme-Linked Immunosorbent Assay;Evaluable Disease;Event;experimental study;Flow Cytometry;former smoker;Gene Expression;Gene Expression Profile;high body mass index;high dimensionality;high risk;High-Risk Cancer;Human;human subject;Immune;Immune response;Immunologic Surveillance;Immunologics;immunoregulation;Immunosuppression;Immunotherapy;improved;Individual;Institution;Investigation;KRASG12D;Link;Lung;lung cancer prevention;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;Measurement;Metformin;Modeling;Molecular;mortality;mouse model;Mus;Mutation;Non obese;non-diabetic;Non-Small-Cell Lung Carcinoma;non-smoker;novel;obese patients;obese person;Obesity;Oral;Outcome;Overweight;Pathway interactions;Patients;Pharmaceutical Preparations;Phase;phase II trial;Play;Population;Populations at Risk;Predisposition;prevent;Preventive;Preventive therapy;primary endpoint;programmed cell death protein 1;programs;protocol development;Randomized;randomized trial;Recording of previous events;Records;Regulatory T-Lymphocyte;Research Personnel;Risk Reduction;Sampling;Serum;Site;Squamous cell carcinoma;Survival Rate;T-Cell Activation;targeted treatment;Testing;Therapeutic;Tissues;tobacco smokers;Tobacco-Associated Carcinogen;transcriptome;transcriptome sequencing;transcriptomics;tumor;tumor-immune system interactions;waist circumference

PROJECT_TITLE: Metformin for chemoprevention of lung cancer in obese subjects at high risk


NIH_SPENDING_CATS: Breast Cancer;Cancer;Women's Health Research

ORG_CITY: Boston

ORG_NAME: TUFTS UNIVERSITY MEDFORD

ORG_STATE: MA

PHR: Project narrative Chemotherapy is the standard of care for triple-negative breast cancer, however up to 25% of patients who receive this treatment will suffer metastatic recurrence within five years. The extracellular matrix is a major component of the tumor microenvironment, which provides structure and support to our tissues, which is known to drive invasion and metastasis. The goal of this project is to investigate how the extracellular matrix contributes to chemoresistance and chemotherapy-induced metastasis.

PI_NAMEs: OUDIN, MADELEINE JULIE (contact)

PROGRAM_OFFICER_NAME: WOODHOUSE, ELIZABETH

PROJECT_TERMS: Adipocytes;Adjuvant Chemotherapy;Affect;Aftercare;Automobile Driving;Breast Cancer Cell;Breast Cancer Patient;Cancer Burden;Caspase;Cathepsins B;cell motility;Cell secretion;cell type;Cessation of life;Chemoresistance;chemotherapy;Clinical;Collagen;Collagen Type IV;Crosslinker;Data;Development;Drug resistance;Endothelial Cells;Environment;Excision;Extracellular Matrix;Extracellular Matrix Proteins;Fibroblasts;Fibronectins;Gene Expression Profile;Glycoproteins;Goals;Human;improved;In Vitro;in vivo;Individual;insight;Invaded;Laminin;Macrophage;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Metastasis Induction;Metastatic/Recurrent;Neoadjuvant Therapy;Neoplasm Metastasis;neoplastic cell;novel;Operative Surgical Procedures;Paclitaxel;Pathway interactions;Patient Care;Patient-Focused Outcomes;Patients;Peptide Hydrolases;Pharmaceutical Preparations;Play;Population;prevent;Process;Property;Proteins;Proteoglycan;Recurrence;Relapse;Research;Residual Cancers;Resistance;response;Role;Sampling;Signal Transduction;standard of care;Structural Protein;Structure;Testing;Therapeutic;therapy outcome;three-dimensional modeling;Tissues;treatment strategy;triple-negative invasive breast carcinoma;tumor;tumor growth;tumor microenvironment;tumor progression;Tumor Tissue;Up-Regulation

PROJECT_TITLE: Investigating mechanisms of chemoresistance in triple-negative breast cancer


NIH_SPENDING_CATS: Cancer;Lung;Lung Cancer;Rare Diseases

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: The proposed basic research is relevant to public health because it focuses on a fundamental step in lung cancer metastasis: invasion. The work will lay the foundation for the development of new strategies to prevent and treat lung cancer morbidity and mortality.

PI_NAMEs: MENDOZA, MICHELLE CHRISTINE (contact)

PROJECT_TERMS: Actins;Adenocarcinoma Cell;Affect;American;Basic Science;Biological Assay;Biosensor;cancer cell;Carcinoma;Cell Line;Cell Physiology;Cells;Computer Models;Data;Development;Disease;Dyspnea;Embryo;Extracellular Matrix;Extracellular Matrix Proteins;ezrin;Fibroblasts;flexibility;Foundations;Glioma;Goals;HSV glycoprotein C;Human;Human Cell Line;Immunofluorescence Immunologic;improved;In Situ;In Vitro;in vivo;innovation;Integrins;Intervention;Invaded;Isogenic transplantation;Knowledge;Lesion;Lung;Lung Adenocarcinoma;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;Measures;Mediating;Membrane;Mesenchymal;Messenger RNA;Methods;Modeling;Molecular;Morbidity - disease rate;mortality;Motility;mouse model;Mus;mutant;Mutation;Myofibroblast;Neoplasm Metastasis;neoplastic cell;Nodule;novel therapeutics;Oncogenic;Operative Surgical Procedures;Outcome;Pain;pancreatic cancer model;Pathway interactions;Patients;Periodicity;Phosphorylation;Phosphorylation Site;Phosphotransferases;prevent;Process;Production;prognostic;prognostic value;programs;PTK2 gene;Public Health;Radiation therapy;Recurrence;Regulation;Research;Respiration;response;Sampling;Signal Transduction;Slice;Source;Spatial Distribution;Stains;Stimulus;Stretching;targeted treatment;Tenascin;Testing;The Cancer Genome Atlas;Tissues;tumor;Tumor Cell Invasion;tumor growth;tumor initiation;Work;Xenograft procedure

PROJECT_TITLE: Cancer invasion: reciprocity between the extracellular matrix and intrinsic ERK signaling


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

ORG_NAME: CLARK ATLANTA UNIVERSITY

PHR: Chemoresistant prostate cancer (PCa) is lethal with no cure. This R01 project will develop a novel class of EED inhibitors that interrupt EED-EZH2 interaction and block noncanonical EZH2 survival signaling in chemoresistant PCa cells. We anticipate to identify several patentable, highly potent and efficacious EED inhibitors with optimized pharmacological profiles and drug-like properties, which can be promptly moved to the next stages of drug development. This project is original, innovative and has high impact on both translational research and patient care.

PI_NAMEs: WU, DAQING  (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: ABCB1 gene;absorption;advanced prostate cancer;analog;androgen independent prostate cancer;anticancer activity;Basic Science;Binding;Biological;Biology;Cancer Patient;Characteristics;Chemicals;Chemoresistance;chemotherapy;Clinical;clinical development;Complex;Death Rate;design;Development;Disease Progression;docetaxel;Dose;Drug Design;drug development;drug discovery;Drug Kinetics;drug synthesis;Ectoderm;Embryo;Enhancers;Epigenetic Process;Excretory function;Goals;good laboratory practice;Growth;Homologous Gene;improved;In Vitro;in vivo;in vivo evaluation;inhibitor;innovation;Interruption;Intervention;Knowledge;Lead;lead optimization;Malignant neoplasm of prostate;Medical;Metabolism;mortality;Mus;NCI Center for Cancer Research;new chemical entity;novel;novel strategies;Oncogenic;Outcome;Pathway interactions;Patient Care;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacology;Phenotype;Polycomb;pre-clinical;Pre-Clinical Model;preclinical development;preclinical efficacy;preclinical safety;Property;prostate cancer cell;prostate cancer model;Prostate Cancer therapy;Protein Kinase;Qualifying;rational design;Reader;Research;research and development;Resistance;S phase;Safety;screening;Signal Transduction;small molecule;Specificity;standard of care;Stat2 protein;Stat3 protein;survivin;Testing;Texas;theranostics;Therapeutic;therapeutic development;Toxic effect;Toxicology;Translating;Translational Research;Universities;Work;Xenograft Model

PROJECT_TITLE: Targeting chemoresistant prostate cancer with novel EED inhibitors


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Prevention;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Basal-like breast cancer has the worst prognosis of all breast cancer types. One of the hurdles to identifying effective targeted therapies is the uncertainty about how the disease arises in the first place. By examining cancer-prone tissues before tumor onset, we hope to identify the path(s) that cells take en route to becoming a basal-like cancer.

PI_NAMEs: JANES, KEVIN A (contact);ZONG, HUI

PROGRAM_OFFICER_NAME: KAI, MIHOKO

PROJECT_TERMS: African American population;Appearance;B-Lymphocytes;BRCA1 gene;Breast;Breast Cancer Genetics;Breast conservation;breast stem cell;breast tumorigenesis;cancer cell;cancer type;Carcinoma;cell type;Cells;Chronology;Clonal Expansion;Collaborations;Data;Disease;Dissociation;Duct (organ) structure;Ecosystem;Endowment;Epithelial Cells;Event;extracellular;functional loss;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genetic Predisposition to Disease;Genetic Transcription;Genetically Engineered Mouse;Genomics;Germ-Line Mutation;Gland;Goals;Heterogeneity;Human;Immune;immune cell infiltrate;Immune system;In Situ;In Situ Lesion;in vivo;Individual;innovation;Intervention;Knock-out;Label;lead candidate;Lesion;Lymphoid Cell;Macrophage;Malignant Breast Neoplasm;Malignant Neoplasms;mammary;Mammary gland;Measures;Mediating;member;Methods;Mitosis;Molecular;mosaic;mosaic analysis;Mus;mutant;Myeloid Cells;Neoplasm Metastasis;neoplastic cell;Noninfiltrating Intraductal Carcinoma;novel;Null Lymphocytes;Oncogenic;Organoids;paracrine;pharmacologic;Phenotype;Play;premalignant;Premalignant Cell;Prevention;Preventive therapy;progenitor;Prognosis;Puberty;Receptor Protein-Tyrosine Kinases;recruit;Role;Route;Signal Transduction;Somatic Mutation;Statistical Data Interpretation;Stress;success;T-Lymphocyte;targeted treatment;Testing;Tissues;TNF gene;tool;TP53 gene;transcription factor;transcriptome;transcriptomics;Trees;tumor;tumor initiation;tumor progression;Tumor Suppressor Proteins;tumorigenesis;Uncertainty;Variant;Visualization;Woman;Work

PROJECT_TITLE: A premalignant chronology of cell-state variability in basal-like breast cancer


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Cancer;Brain Disorders;Cancer;Neurosciences;Rare Diseases

ORG_CITY: CHAMPAIGN

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

ORG_STATE: IL

PHR: NARRATIVE Glioblastoma is the most aggressive and deadly form of brain cancer whose poor clinical outcome stems from its diffuse invasion throughout the brain and drug resistance. This project will develop and thoroughly characterize a tissue engineering platform to investigate pathophysiological processes responsible for invasive spreading, therapeutic resistance, and poor survival.

PI_NAMEs: HARLEY, BRENDAN A. (contact)

PROGRAM_OFFICER_NAME: BECKER, STEVEN

PROJECT_TERMS: Acceleration;Address;Alkylating Agents;Animal Model;Animals;anti-cancer;Automobile Driving;Behavior;Benchmarking;Biocompatible Materials;bioinformatics tool;Biological Assay;Biophysics;Blood Vessels;Brain;Brain Neoplasms;Cancer Model;Cell Line;Cells;Clinic;Clinical;detection limit;Diffuse;Dimensions;Disparate;DNA;DNA Modification Process;DNA Repair;drug candidate;Drug resistance;Engineering;Evaluation;Excision;Failure;Gelatin;Generations;Glioblastoma;Glioma;Goals;High-dimensional Modeling;Human;Hyaluronic Acid;Hydrogels;Imaging Device;in vivo;in vivo evaluation;insight;Invaded;Libraries;Link;Malignant neoplasm of brain;Malignant Neoplasms;Mediating;Meta-Analysis;Metabolic;Methyltransferase;Microfluidics;migration;mimetics;miniaturize;Modeling;Molecular Weight;mortality;neurovascular;novel;novel therapeutics;Operative Surgical Procedures;Outcome;Patients;Pattern;Pericytes;Physiological;Play;pressure;Process;programs;Proliferating;Proteins;Recurrence;repaired;Resistance;Resources;response;Role;Signal Transduction;Specimen;standard of care;stem;Surgical margins;Survival Rate;Technology;temozolomide;therapeutic evaluation;therapy resistant;Tissue Engineering;Tissue Model;tumor;Variant;Work;Xenograft procedure

PROJECT_TITLE: Perivascular tissue models to overcome MGMT-mediated temozolomide resistance in glioblastoma

STUDY_SECTION: CMT

STUDY_SECTION_NAME: Cellular and Molecular Technologies Study Section[CMT]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Services;Palliative Care;Prevention;Primary Health Care;Rehabilitation;Women's Health Research

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: PUBLIC HEALTH RELEVANCE The numbers of breast cancer survivors are increasing and their symptom burden after treatment is significant. Despite a growing evidence base of symptom management and risk reduction strategies, use of these activities in primary care practice remains suboptimal. This study engages critical stakeholders in identifying and prioritizing evidence based activities to enhance breast cancer survivorship care and has potential to impact implementation strategies used throughout the U.S. for long-term care for patients with a history of breast cancer.

PI_NAMEs: CRABTREE, BENJAMIN F;HUDSON, SHAWNA V. (contact)

PROGRAM_OFFICER_NAME: SARMA, ELIZABETH ANNE

PROJECT_TERMS: Address;Adopted;Adoption;Aftercare;American Cancer Society;Biological Response Modifier Therapy;Breast Cancer survivor;Breast Cancer survivorship;Breast Cancer Treatment;Cancer Model;Cancer Survivor;Cancer Survivorship;cancer survivorship care;Caring;chemotherapy;Chronic Disease;Clinical;Clinical Management;clinically actionable;Code;Complex;concept mapping;Consensus;Cost Analysis;Counseling;design;Development;Diagnosis;Diagnostic;Early Diagnosis;Early treatment;Education;Effectiveness;effectiveness trial;Evaluation;evidence base;experience;follow-up;Future;Guidelines;Health behavior;Healthcare;Healthcare Systems;hormone therapy;Hybrids;implementation strategy;implementation/effectiveness;Individual;Information Systems;innovation;Intervention;Interview;Knowledge;Learning;Literature;Long-Term Care;Long-Term Effects;Malignant Breast Neoplasm;Mental Health Services;Methods;Modeling;Monitor;multidisciplinary;Oncology;Patient Care;Patients;Policies;Policy Maker;Population;Positioning Attribute;Primary Care;primary care practice;primary care setting;Process;Protocols documentation;Provider;Public Advocacies;public health relevance;Radiation;Randomized;receptor;Recommendation;Recording of previous events;Recurrence;Research;Research Design;Research Personnel;research study;Risk Management;Risk Reduction;Second Primary Cancers;Self Management;Services;Site;Structure;survivorship;Symptom Burden;symptom management;Testing;Translating;translational potential;uptake;Waiting Lists;Work

PROJECT_TITLE: Adapting and implementing evidence-based breast cancer follow-up in primary care

STUDY_SECTION: SIHH

STUDY_SECTION_NAME: Science of Implementation in Health and Healthcare Study Section[SIHH]


ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

PHR: PROJECT NARRATIVE Triple Negative Breast Cancer (TNBC) is a highly aggressive disease that has limited treatment options. This proposal focuses on determining if a protein called YES1 may underlie the malignancy associated with TNBC and the molecular pathways it uses to cause poor patient outcomes. This work will also provide a proof-of- concept in model systems testing the possibility of inhibiting YES1 with drugs that may ultimately lead to a more effective approach for treating TNBC.

PI_NAMEs: KERI, RUTH A. (contact)

PROGRAM_OFFICER_NAME: XU, WANPING

PROJECT_TERMS: Adhesions;Architecture;Automobile Driving;Biological Models;Breast Cancer Cell;Breast Cancer Patient;cancer initiation;cell growth;Cell Nucleus;Cell Survival;chemotherapy;Chromosomal Instability;Collection;Coupled;Cytotoxic Chemotherapy;Data;Defect;differential expression;Disease;drug efficacy;Drug Targeting;Ensure;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;ERBB2 gene;Estrogens;Event;expectation;extracellular;Family;Family member;Functional disorder;Gamma-H2AX;Genome Stability;Genomic Instability;Genomics;Goals;Growth;Heat-Shock Proteins 70;Heterogeneity;improved;Individual;inhibitor;innovation;insight;live cell imaging;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Metastatic/Recurrent;micronucleus;Mitosis;Mitotic;Molecular;Molecular Chaperones;Motility;neoplastic cell;new therapeutic target;novel;novel therapeutic intervention;Nuclear;Oncogenic;Outcome;overexpression;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Phosphotransferases;Play;Precision therapeutics;Process;Progesterone;Proliferating;Protein Tyrosine Kinase;Proteins;receptor;receptor expression;Receptor Signaling;refractory cancer;Reporting;Resistance;response;restoration;Role;Signal Pathway;Signal Transduction;src-Family Kinases;survivorship;targeted treatment;taxane;Testing;Therapeutic;therapeutic target;Toxic effect;transcription factor;transcriptomics;triple-negative invasive breast carcinoma;tumor;tumor progression;Work;YES1 gene

PROJECT_TITLE: Discovering the role of YES1 in triple negative breast cancer

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Colorectal Cancer;Digestive Diseases;Genetics;Nutrition;Obesity;Prevention

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: PROJECT NARRATIVE. Approximately 42%of American adults are obese, and this condition is strongly related to the development of colorectal cancer. Innovative lifestyle strategies to treat obesity and reduce colorectal cancer risk are critically needed. The proposed research will demonstrate that time-restricted eating, a type of intermittent fasting, is an effective therapy to help obese individuals reduce and control their body weight and prevent the development of colorectal cancer.

PI_NAMEs: TUSSING-HUMPHREYS, LISA  (contact);VARADY, KRISTA AMY

PROGRAM_OFFICER_NAME: EMENAKER, NANCY J

PROJECT_TERMS: Address;Adenomatous Polyps;Adherence;Adult;adult obesity;Affect;American;Animals;anti-cancer;Apoptosis;arm;Behavioral Sciences;Biological;Biological Markers;Biometry;Blood;Blood Pressure;Body Composition;Body fat;Body mass index;Body Weight;Body Weight decreased;Caloric Restriction;Calories;cancer biomarkers;Cancer Etiology;cell growth;Cessation of life;Chronic Disease;circulating biomarkers;Clinical;Clinical Research;Clinical Trials;Colon;colon carcinogenesis;colon tumorigenesis;Colorectal Cancer;colorectal cancer risk;common treatment;Consumption;cytokine;Data;Development;Diagnosis;dieting;Differentiation Antigens;Disease;DNA Damage;Eating;effective therapy;Environmental Exposure;Epigenetic Process;experience;feasibility testing;Food;Gastroenterology;Gene Expression;Gene Expression Profile;Gene Expression Regulation;gene repression;Genetic;glucose metabolism;Health;Heredity;Hour;human old age (65+);Immune;Immune System Diseases;improved;Incidence;Individual;Inflammation;Inflammatory;inflammatory marker;innovation;Insulin Resistance;Insulin-Like Growth Factor I;Interleukin-6;Intermittent fasting;Intervention;Isoprostanes;Life Style;lifestyle intervention;Link;Maintenance;Malignant Neoplasms;Mediating;Metabolic;Metabolic dysfunction;Methods;modifiable lifestyle factors;modifiable risk;Molecular;molecular marker;Monitor;Mucositis;Mucous Membrane;muscle form;Mutation;National Cancer Institute;novel;Nutritional Science;obese person;Obesity;obesity treatment;Oxidative Stress;Pathway interactions;Persons;Phase;Pilot Projects;Population;prevent;Process;Proliferating;protective effect;Randomized;reduced food intake;Research;Risk;Risk Factors;Risk Marker;Risk Reduction;Safety;Specific qualifier value;systemic inflammatory response;Testing;Thinness;Time;Time-restricted feeding;Tissues;tool;United States;Up-Regulation;Water;Weight;Weight maintenance regimen

PROJECT_TITLE: Effects of Time-restricted Eating versus Daily Continuous Calorie Restriction on Body Weight and Colorectal Cancer Risk Markers among Adults with Obesity