Completion DEGREE INSTITUTION AND LOCATION

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1 OMB No and (Rev. 10/15 Approved Through 10/31/2018) BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. NAME: Emily Wilson, Ph.D. era COMMONS USER NAME (credential, e.g., agency login): POSITION TITLE: Professor EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) Completion DEGREE INSTITUTION AND LOCATION Date FIELD OF STUDY (if applicable) MM/YYYY Utah State University, Logan, UT B.S Biology Utah State University, Logan, UT M.S Biochemistry Emory State University, Atlanta, GA Ph.D Biochemistry Vanderbilt University, Nashville, TN Postdoc 1991 Pharmacology A. Personal Statement: My research has focused on the role of mechanical forces in vascular and lymphatic remodeling. Through the years, I have specifically focused on how mechanical forces are sensed and translated into changes in cellular behavior and phenotype and how these changes contribute to vascular diseases such as hypertension, aneurysm formation and aging. During this process, we have developed methods to study changes at the molecular and cellular level, in isolated blood vessels and using whole animal and genetic models. We have utilized systems to expose vascular muscle cells to stress in order to identify the role of integrin-ecm interaction in transmitting signals and to identify transcription factors that are involved in vascular smooth muscle phenotypic modulation. We have also developed an ex vivo culture systems that can be used to maintain mouse carotid arteries in culture with precise control of mechanical environment and with the ability to measure biomechanical properties in real time. Additionally, we have used mouse models to measure the effects of altered biomechanical properties on vascular remodeling in mouse models of thoracic aortic aneurysms and to assess alterations in the biomechanical properties in response to these genetic changes. More recently we have transferred this knowledge gained to study changes in lymphatic structure, and function in response to chronic alteration in lymph flow and in a model of lymphatic obstruction. We have shown that there is a corresponding change in gene expression and functional changes with each of these models. Our ongoing research will focus on how lymphatic muscle is altered under chronic pathological changes. I will contribute to mentoring of trainees in these areas and have active collaborations with many of the other mentors that are participating in this T32 proposal. B. Positions and Honors Associate Vice President for Academic Affairs, Texas A&M Health Science Center, Bryan TX 2014-Present Professor, Department of Medical Physiology (formerly Systems Biology and Translational Medicine), College of Medicine, Texas A&M Health Science Center, College Station TX 09/01/ Executive Associate Dean, School of Graduate Studies, Texas A&M Health Science Center, College Station TX 01/01/ Assistant Vice President for Graduate Studies, Texas A&M Health Science Center, College Station, TX, 09/01/09-01/01/2011 Director, Office of Graduate Studies, Texas A&M Health Science Center College of Medicine, College Station, TX 2007-present Assoc Professor: Dept of Systems Biology and Translational Medicine, Texas A&M Univ System HSC, College Station, TX 01/06-present

2 Assoc Professor: Dept of Medical Physiology, Texas A&M Univ System HSC, College Station, TX 09/05-12/05 Asst Prof: Dept of Med Physiology, Texas A&M Univ System HSC, College Station, TX 01/97-08/05. Asst Research Biochemist; Cardiovascular Research Inst and the Div of Nephrology, Univ of California, San Francisco (San Francisco, CA) 01/91-01/97 Associate; Howard Hughes Medical Inst, Vanderbilt Univ School of Medicine, (Nashville, TN), /1991, Dr. D. Martin Watterson. Research Associate, Dept of Pharmacology, Vanderbilt Univ School of Medicine (Nashville, TN) /91, Dr. D. Martin Watterson. Professional Service Grant Reviews (Partial List) American Heart Association (Western Affiliates): 4A Atherosclerosis, Thrombosis and Vascular Wall Biology ( ) American Heart Association (Western Affiliates): 3B Cell & Basic Molecular Biology Cardiovascular Development, Immunology & Microbiology (2005, 2006, 2007, 2009). American Heart Association, National, Vascular Wall Biology 1 Study Group, October April 2006 October 2006 NIH Special Emphasis Panel Vascular Biology: Feb June 2006 October 2006, Feb 2007, June 2007, Feb 2008, June 2008, October Feb 2009, October NIH F10 Fellowship Review Panel. March 2007, June 2007, May 2010 National Center for Complementary and Alternative Medicine (NCCAM / NIH) Developmental Centers for Research on Complementary and Alternative Medicine: Phase I (DCRC I) and Phase II (DCRC II) Nov 12-14, 2007 NIH--Special Emphasis Panel to Review Competitive Hemotology/Thrombosis Supplements (June 25, 26, 2009). NIH Special Emphasis Panel to Review Competitive Supplements Vascular Biology ZRG1 VH-B (95) (July 8, 9, 2009) Charter member of NIH Vascular Cell and Molecular Biology Study Section Special Emphasis Panel/Scientific Review Group 2015/01 ZRG1 VH-C (80) AREA/R15 Special Emphasis Panel/Scientific Review Group 2015/01 ZRG1 DKUS-L (11) 2014-Small Business Grants NIH Vascular Cell and Molecular Biology Study Section Feb 2015 (Ad hoc) Societies: ASBMB, ASCB, APS, NAVBO, Microcirculation, AHA Journal Review: Circulation Research, Circulation, Hypertension, J Vasc Biology, Cardiovacular Research, PNAS, C. Contributions to Science 1. Identification of Sphingolipid breakdown products as cellular messengers. During my graduate training my research was the first to identify sphingolipid breakdown products as cellular regulators. I showed that sphingosine inhibited neutrophil activation in response to a number of known activators and identified protein kinase C as the site of action of sphingosine. We also went on to show that sphingosine modulated neutrophil migration, the response to growth factors, and maturation. a) Wilson E, Olcott MC, Bell RM, Merrill AH Jr, Lambeth JD. Inhibition of the oxidative burst in human neutrophils by sphingoid long-chain bases. Role of protein kinase C in activation of the burst. J Biol Chem Sep 25;261(27): PMID:

3 b) Wilson E, Wang E, Mullins RE, Uhlinger DJ, Liotta DC, Lambeth JD, Merrill AH Jr. Modulation of the free sphingosine levels in human neutrophils by phorbol esters and other factors. J Biol Chem Jul 5;263(19): PMID: c) Wilson E, Rice WG, Kinkade JM Jr, Merrill AH Jr, Arnold RR, Lambeth JD. Protein kinase C inhibition by sphingoid long-chain bases: effects on secretion in human neutrophils. Arch Biochem Biophys Nov 15;259(1): PMID: Modulation of smooth muscle phenotype by mechanical forces. My research was among the first to show that altered mechanical forces contribute to the growth and differentiation of smooth muscle cells. We showed that the type of extracellular matrix that the cells associated with altered the response to mechanical forces and that different integrins were involved in signaling the response. We identified a number of genes that were modulated by mechanical forces and identified transcription factors and stretch responsive elements in the promoter of several of these gene. This series of studies was seminal in our understanding of how vascular cells sense and respond to changes in mechanical forces. a) Sudhir K, Wilson E, Chatterjee K, Ives HE. Mechanical strain and collagen potentiate mitogenic activity of angiotensin II in rat vascular smooth muscle cells. J Clin Invest Dec;92(6): doi: /JCI PMID: ; PMCID: PMC b) Wilson E, Mai Q, Sudhir K, Weiss RH, Ives HE. Mechanical strain induces growth of vascular smooth muscle cells via autocrine action of PDGF. J Cell Biol Nov;123(3): PMID: ; PMCID: PMC c) Wilson E, Vives F, Collins T, Ives HE. Strain-responsive regions in the platelet-derived growth factor-a gene promoter. Hypertension Jan;31(1 Pt 2): PMID: d) Wilson E, Sudhir K, Ives HE. Mechanical strain of rat vascular smooth muscle cells is sensed by specific extracellular matrix/integrin interactions. J Clin Invest Nov;96(5): doi: /JCI PMID: ; PMCID: PMC Development and use of ex vivo systems to culture mouse carotid arteries under controlled mechanical environments and to analyze alterations in biomechanical properties. In conjunction with Dr. Jay Humphrey (currently at Yale University), we developed an ex vivo mouse carotid culture system in which we could expose mouse carotid arteries to precise changes in shear stress, circumferential wall stress and axial stress. This system allows us to measure in real time changes in the biomechanics of the vessels in response to the changes in mechanical forces. We have used this system to measure the effects specific extracellular matrix proteins and contractile proteins on the remodeling process. This system and the data gained from it have contributed to our overall knowledge of how the vasculature respond to mechanical forces and the role of specific ECM proteins in this process. a) Gleason RL, Gray SP, Wilson E, Humphrey JD. A multiaxial computer-controlled organ culture and biomechanical device for mouse carotid arteries. J Biomech Eng Dec;126(6): PMID: b) Gleason RL, Wilson E, Humphrey JD. Biaxial biomechanical adaptations of mouse carotid arteries cultured at altered axial extension. J Biomech. 2007;40(4): doi: /jbiomech PMID: c) Eberth JF, Taucer AI, Wilson E, Humphrey JD. Mechanics of carotid arteries in a mouse model of Marfan Syndrome. Ann Biomed Eng Jun;37(6): doi: /s PMID: ; PMCID: PMC d) Eberth JF, Popovic N, Gresham VC, Wilson E, Humphrey JD. Time course of carotid artery growth and remodeling in response to altered pulsatility. Am J Physiol Heart Circ Physiol Dec;299(6):H doi: /ajpheart PMID: ; PMCID: PMC Identification of TGF-b as a key mediator of vascular changes in response to mechanical forces. Using a porcine aortic coarctation model, we showed that TGF-b signaling was upregulated in regions high pressure and that this increased signaling was due to increased activation pre-existing TGF-b. This is observation has led to our hypothesis that the latent TGF-b complex is a sensor for vascular wall stresses.

4 We have ongoing studies that will focus on identifying mechanisms by which alterations in vascular wall stresses regulate TGF-b activation and downstream signaling to play important roles in hypertension, aneurysm formation, and aging. a) Popovic N, Bridenbaugh EA, Neiger JD, Hu JJ, Vannucci M, Mo Q, Trzeciakowski J, Miller MW, Fossum TW, Humphrey JD, Wilson E. Transforming growth factor-beta signaling in hypertensive remodeling of porcine aorta. Am J Physiol Heart Circ Physiol Dec;297(6):H doi: /ajpheart PMID: ; PMCID: PMC b) Howell DW, Popovic N, Metz RP, Wilson E. Regional changes in elastic fiber organization and transforming growth factor β signaling in aortas from a mouse model of marfan syndrome. Cell Tissue Res Dec;358(3): doi: /s PMID: Short-term mesenteric lymphatic adaptation to altered shear stresses and pressure. We have developed two surgical models in bovines to test the response of mesenteric lymphatic vessels to chronic exposure to increases in lymph flow (shear stress) or to an obstruction of the lymphatic vessel resulting increased intraluminal pressure. We found that in a model of mesenteric venous hypertension which resulted in increased edema with resulting increases in lymph flow caused functional changes in the lymphatic vessels that were consistent with a decrease in lymphatic pump activity and increase in passive flow. We also found (manuscript in preparation) that there were consistent changes in gene expression. These studies are the first to show that there is functional remodeling of lymphatic vessels in response to long-term changes in lymph flow. a) Quick CM, Criscione JC, Kotiya A, Dongaonkar RM, Hardy J, Wilson E, Gashev AA, Laine GA, Stewart RH. Functional adaptation of bovine mesenteric lymphatic vessels to mesenteric venous hypertension. Am J Physiol Regul Integr Comp Physiol Jun 15;306(12):R doi: /ajpregu PMID: ; PMCID: PMC b) Dongaonkar RM, Nguyen TL, Quick CM, Heaps CL, Hardy J, Laine GA, Wilson E, Stewart RH. Mesenteric lymphatic vessels adapt to mesenteric venous hypertension by becoming weaker pumps. Am J Physiol Regul Integr Comp Physiol Mar 1;308(5):R doi: /ajpregu PMID: c) Dongaonkar RM, Nguyen TL, Quick CM, Hardy J, Laine GA, Wilson E, Stewart RH. Adaptation of mesenteric lymphatic vessels to prolonged changes in transmural pressure. Am J Physiol Heart Circ Physiol Jul 15;305(2):H doi: /ajpheart PMID: ; PMCID: PMC Complete List of Published Works in MyBibliography (61) D. Research Support Completed Research Support (Wilson E PI; Friedman J Co-I) 03/01/12-02/28/14 Texas A&M Health Science Center Women s Health in Neuroscience Initiative Gender differences in thoracic aortic aneurysms and cerebral aneurysms This proposal is aimed at obtaining molecular data relating to the differences in susceptibility of men and women to aneurysm development and dissections. Epidemiological studies show that men are at greater risk of developing thoracic aortic aneurysms and have worse outcomes than women. In contrast, postmenopausal women are more likely to have worse outcomes from intracranial aneurysms. The goal of this study will be to determine the relationship between sex steroids and smooth muscle phenotypic changes associated with aneurysm development.

5 (Wilson E Co-I; Friedman J Co-I) 03/01/11-02/28/12 Texas Brain & Spine Institute Seed Grant Culture and characterization of vascular smooth muscle cells from intracranial aneurysms We hypothesize that the vascular smooth muscle cells from the sites of aneurysms may show altered phenotypes from control cells that may increase their susceptibility to apoptosis or show altered gene expression that result in the increased breakdown of the vascular wall both of which contribute to rupture and subsequent hemorrhaging. R01 HL (Stewart RH PI; Wilson E PI) 07/01/09-06/30/11 Short-term mesenteric lymphatic adaptation to trauma-related intestinal edema The central hypothesis for the proposed research is that mesenteric lymphatic vessels will adapt to mesenteric venous hypertension and intestinal edema by becoming better conduits and will adapt to downstream lymphatic obstruction by becoming better pumps. R21 (Wilson E PI) 07/01/09-06/30/11 TGF-beta complex serves as a mechanosensor in the vascular wall We will use this system to investigate the hypothesis that changes in wall stress in response to increased blood pressure modulates the bioavailability of TGF-beta, which contributes to arterial growth and remodeling R01 HL (Heaps CL PI; Wilson E Co-I) 08/01/06-07/31/11 Chronic Coronary Occlusion, Exercise Training and NO The primary goal of this research is to determine the cellular mechanisms responsible for effects of exercise training on nitric oxide bioavailability and role in the underlying setting of chronic coronary artery occlusion and collateral-dependent perfusion. R21 (Humphrey JD PI; Wilson E Co-I) 08/01/08-06/30/10 Constrictor/mitogen induced remodeling of cerebral arterioles The overall goal of this R21 application is to quantify, for the first time, biomechanical, functional, and immunohistochemical changes that result from blood clot associated constrictors, smooth muscle mitogens, and extracellular matrix cross-linkers that are presented to the adventitial surface of cerebral arterioles (as in subarachnoid hemorrhage) with particular attention to expected short-term (3-5 days) structural and functional remodeling and the potential of preventing or reducing such changes.