title: Translational systems approaches to the biology of inflammation and healing.
abstract: Inflammation is a complex, non-linear process central to many of the diseases that affect both developed and emerging nations. A systems-based understanding of inflammation, coupled to translational applications, is therefore necessary for efficient development of drugs and devices, for streamlining analyses at the level of populations, and for the implementation of personalized medicine. We have carried out an iterative and ongoing program of literature analysis, generation of prospective data, data analysis, and computational modeling in various experimental and clinical inflammatory disease settings. These simulations have been used to gain basic insights into the inflammatory response under baseline, gene-knockout, and drug-treated experimental animals for in silico studies associated with the clinical settings of sepsis, trauma, acute liver failure, and wound healing to create patient-specific simulations in polytrauma, traumatic brain injury, and vocal fold inflammation; and to gain insight into host-pathogen interactions in malaria, necrotizing enterocolitis, and sepsis. These simulations have converged with other systems biology approaches (e.g., functional genomics) to aid in the design of new drugs or devices geared towards modulating inflammation. Since they include both circulating and tissue-level inflammatory mediators, these simulations transcend typical cytokine networks by associating inflammatory processes with tissue/organ impacts via tissue damage/dysfunction. This framework has now allowed us to suggest how to modulate acute inflammation in a rational, individually optimized fashion. This plethora of computational and intertwined experimental/engineering approaches is the cornerstone of Translational Systems Biology approaches for inflammatory diseases.
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. vodovotz@upmc.edu
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
authors.forename: Gregory
authors.initials: G
authors.lastname: Constantine
authors.forename: James
authors.initials: J
authors.lastname: Faeder
authors.forename: Qi
authors.initials: Q
authors.lastname: Mi
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rubin
authors.forename: John
authors.initials: J
authors.lastname: Bartels
authors.forename: Joydeep
authors.initials: J
authors.lastname: Sarkar
authors.forename: Robert H
authors.initials: RH
authors.lastname: Squires
authors.forename: David O
authors.initials: DO
authors.lastname: Okonkwo
authors.forename: Jörg
authors.initials: J
authors.lastname: Gerlach
authors.forename: Ruben
authors.initials: R
authors.lastname: Zamora
authors.forename: Shirley
authors.initials: S
authors.lastname: Luckhart
authors.forename: Bard
authors.initials: B
authors.lastname: Ermentrout
authors.forename: Gary
authors.initials: G
authors.lastname: An
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D008954:Models, Biological; D049490:Systems Biology; D014945:Wound Healing / Q000276:immunology*
chemical_list: D016207:Cytokines