title: Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation.
abstract: BACKGROUND
  Cerebral cavernous malformation (CCM) is a hemorrhagic stroke disease affecting up to 0.5% of North Americans that has no approved nonsurgical treatment. A subset of patients have a hereditary form of the disease due primarily to loss-of-function mutations in KRIT1, CCM2, or PDCD10. We sought to identify known drugs that could be repurposed to treat CCM.
  
  
  RESULTS
  We developed an unbiased screening platform based on both cellular and animal models of loss of function of CCM2. Our discovery strategy consisted of 4 steps: an automated immunofluorescence and machine-learning-based primary screen of structural phenotypes in human endothelial cells deficient in CCM2, a secondary screen of functional changes in endothelial stability in these same cells, a rapid in vivo tertiary screen of dermal microvascular leak in mice lacking endothelial Ccm2, and finally a quaternary screen of CCM lesion burden in these same mice. We screened 2100 known drugs and bioactive compounds and identified 2 candidates, cholecalciferol (vitamin D3) and tempol (a scavenger of superoxide), for further study. Each drug decreased lesion burden in a mouse model of CCM vascular disease by ≈50%.
  
  
  CONCLUSIONS
  By identifying known drugs as potential therapeutics for CCM, we have decreased the time, cost, and risk of bringing treatments to patients. Each drug also prompts additional exploration of biomarkers of CCM disease. We further suggest that the structure-function screening platform presented here may be adapted and scaled to facilitate drug discovery for diverse loss-of-function genetic vascular disease.
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Gibson
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Weiquan
authors.initials: W
authors.lastname: Zhu
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Chadwick T
authors.initials: CT
authors.lastname: Davis
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Jay A
authors.initials: JA
authors.lastname: Bowman-Kirigin
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Aubrey C
authors.initials: AC
authors.lastname: Chan
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Jing
authors.initials: J
authors.lastname: Ling
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Walker
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Luca
authors.initials: L
authors.lastname: Goitre
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Simona
authors.initials: S
authors.lastname: Delle Monache
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Saverio Francesco
authors.initials: SF
authors.lastname: Retta
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Yan-Ting E
authors.initials: YT
authors.lastname: Shiu
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Allie H
authors.initials: AH
authors.lastname: Grossmann
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Thomas
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lesniewski
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.).
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Whitehead
authors.affiliation: From the Program in Molecular Medicine (C.C.G., W.Z., C.T.D., J.A.B.-K., A.C.C., J.L., A.H.G., K.R.T., K.J.W., D.Y.L.), Department of Bioengineering (C.C.G., Y.-T.E.S.), Department of Medicine (C.C.G., W.Z., K.R.T., D.Y.L.), Department of Human Genetics (C.T.D.), Department of Oncological Sciences (A.C.C., D.Y.L.), Division of Geriatrics, Department of Medicine (A.E.W., A.J.D., L.A.L.), Division of Nephrology and Hypertension, Department of Medicine (Y.-T.E.S.), Department of Pathology (A.H.G.), Division of Cardiology, and Department of Medicine (K.J.W., D.Y.L.), University of Utah, Salt Lake City, UT; Recursion Pharmaceuticals, LLC, Salt Lake City, UT (C.C.G., D.Y.L.); CCM Italia, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy (L.G., S.F.R.); CCM Italia, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy (S.D.M.); Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT (A.J.D., L.A.L.); The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (D.Y.L.); and Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT (K.J.W., O.Y.L.). dean.li@u2m2.utah.edu.
authors.forename: Dean Y
authors.initials: DY
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002762:Cholecalciferol / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D058492:Drug Repositioning / Q000379:methods*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D020786:Hemangioma, Cavernous, Central Nervous System / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016896:Treatment Outcome
chemical_list: D016166:Free Radical Scavengers; D002762:Cholecalciferol
keywords: cerebrovascular disorders; endothelium; genetics; hemorrhage; stroke