BIOMEDICAL SCIENCES GRADUATE PROGRAM SUMMER 2018

Transcription

1 THE OHIO STATE UNIVERSITY BIOMEDICAL SCIENCES GRADUATE PROGRAM SUMMER 2018 T.M. Ayodele Adesanya Ph.D. Candidate Graduate Interdisciplinary Specialization in Biomedical, Clinical, and Translational Science MG53 Protects Aortic Valve Interstitial Cells from Membrane Injury and Fibrocalcific Remodeling July 31, 2018 DHLRI :00 a.m.

2 VITA Born Dallas, Texas Phillips Academy Andover S.B. (Biological Chemistry), A.B. (Chemistry), A.B. (Biological Sciences); The University of Chicago 2009 Present M.D./Ph.D. Candidate; The Ohio State University College of Medicine (Biomedical Sciences Graduate Program) COMMITTEE MEMBERS Dr. Jianjie Ma (Advisor) Dr. Joanna Groden Dr. Peter Mohler Dr. Joy Lincoln Dr. Hua Zhu

3 ABSTRACT The aortic valve of the heart experiences constant mechanical stress under physiological conditions, and maladaptive valve injury responses contribute to the development of valvular heart disease (VHD). Here, we test the hypothesis that MG53, an essential cell membrane repair protein, can protect valvular cells from physical injury and fibrocalcific remodeling processes associated with VHD. We found that MG53 is expressed in pig and human patient aortic valves and observed aortic valve disease in aged Mg53-/- mice. Furthermore, aortic valves of Mg53-/- mice showed increased uptake of Evans blue dye, indicating compromised cell membrane integrity. In vitro studies demonstrated that MG53 protects primary valve interstitial cells (VICs) from mechanical injury and that, in addition to mediating membrane repair, recombinant human MG53 (rhmg53) can enter VICs and suppress TGF- -dependent activation of fibrocalcific signaling. Together, our data characterize VIC membrane repair as a novel mechanism of protection against valvular remodeling and assess potential in vivo roles of MG53 in preventing VHD.

4 RECENT ABSTRACTS AND PRESENTATIONS Adesanya TM, Russell M, Zhou X, Zhu H, Tan T, Park KH, Lincoln J, Ma J. MG53-mediated protection in heart valve biology Poster Keystone Symposia Conference: Molecular Mechanisms of Heart Development; Keystone, Colorado 2017 Poster Biophysical Society Annual Meeting; New Orleans, Louisiana 2016 Oral Biennial Meeting on Heart Valve Biology and Tissue Engineering; Hilton Head, South Carolina (meeting cancelled due to Hurricane Matthew) 2014 Poster Dorothy M. Davis Heart and Lung Research Institute Research Day; The Ohio State University, Columbus, Ohio 2014 Poster Biennial Meeting on Heart Valve Biology and Tissue Engineering; The Royal Society, London, England 2014 Poster Trainee Research Day; The Ohio State University, Columbus, Ohio Ma H, Zhou X, Wang X, Wu J, Gumpper K, Tan T, Adesanya TM, Yang C, Zheng Y, Chandler H, Zhou J, Ma J, Zhu H. MG53 interacts with cardiolipin to protect mitochondria from ischemia-reperfusioninduced oxidative stress Poster Biophysical Society Annual Meeting; New Orleans, Louisiana D Amico R, Adesanya TM, Hatfield S, Willis S, Sturdivant R, Foraker RE, Binkley P, Abraham W, Breathett K. Patient perceptions on improving follow-up after heart failure hospitalization Poster American Heart Association Scientific Sessions; New Orleans, Louisiana Russell M, Adesanya TM, Zhou X, Zhu H, Tan T, Park KH, Lincoln J, Ma J. MG53-mediated protection in heart valve biology Oral Annual Biomedical Research Conference for Minority Students; Seattle, Washington *One of 8 (out of 81) students selected to have an oral presentation in the Physiological Sciences Section 2015 Poster Dorothy M. Davis Heart and Lung Research Institute Research Day; The Ohio State University, Columbus, Ohio *Second Place (out of 10) in the Undergraduate Section

5 Zhu H, Alessandro Lagana, Veneziano D, Adesanya TM, Mohler PJ, Nishi M, Takeshima H, Kilic A. Serum microrna-378 as a novel diagnostic biomarker for myocardial infarction Poster American Heart Association Scientific Sessions; Chicago, Illinois Adesanya TM, Spata T, Bobek D, Whitson BA, Parthasarathy S, Mohler PJ, Higgins RSD, Kilic A. A catheter-based, ovine model of myocardial infarction using autologous platelets Poster Dorothy M. Davis Heart and Lung Research Institute Research Day; The Ohio State University, Columbus, Ohio *Third Place (out of 54) in the Pre-doctoral Section

6 RECENT PUBLICATIONS Adesanya TM, Russell M, Park KH, Zhou X, Sermersheim MA, Gumpper K, Tan T, Whitson BA, Janssen PM, Lincoln J, Zhu H, Ma J. MG53 protects aortic valve interstitial cells from membrane injury and fibrocalcific remodeling. J Am Heart Assoc. (Submitted) Chandler HL, Tan T, Yang C, Gemensky-Metzler AJ, Wehrman R, Jiang Q, Peterson C, Wang Q, Kaili D, Adesanya TM, Yi F, Ma J, Zhu H. MG53 promotes corneal wound healing and mitigates fibrotic remodeling. Commun Biol. (Submitted) El Refaey M, Xu L, Gao Y, Canan BD, Adesanya TM, Warner SC, Akagi K, Symer DE, Mohler PJ, Ma J, Janssen PM, Han R. In vivo genome editing restores dystrophin expression and cardiac function in dystrophic mice. Circ Res Sep 29;121(8): Breathett K, D Amico R, Adesanya TM, Hatfield S, Willis S, Sturdivant RX, Foraker RE, Smith S, Binkley P, Abraham WT, Peterson PN. Patient perceptions on facilitating follow-up after heart failure hospitalization. Circ Heart Fail Jun;10(6). pii:e Sermersheim MA, Park KH, Gumpper K, Adesanya TM, Song K, Tan T, Ren X, Yang JM, Zhu H., MicroRNA regulation of autophagy in cardiovascular disease. Front Biosci (Landmark Ed) Jan 1;22: Xie N, Li Z, Adesanya TM, Guo W, Liu Y, Fu M, Kilic A, Tan T, Zhu H, Xie X. Transplantation of placenta-derived mesenchymal stem cells enhances angiogenesis after ischemic limb injury in mice. J Cell Mol Med Aug 18. Ma H, Liu J, Bian Z, Cui Y, Zhou X, Zhang B, Adesanya TM, Yi F, Park KH, Tan T, Chen Z, Zhu H. Effect of metabolic syndrome on mitsugumin 53 expression and function. PLoS One May 7;10(5):e Adesanya TM. The Physician Researcher Initiative: Streamlining SNMA representation in translational medicine through programming and partnership. JSNMA. Spring 2015:5-7. Adesanya TM, Kilic A. Dealing with a porcelain aorta during coronary artery bypass grafting. Case Rep Surg. 2014; 2014: Adesanya TM, Daniel VC, Kilic A. Surgical lung resection in a patient with an existing left ventricular assist device. Exp Clin Cardiol Fall;20(10):

7 Zhang B, Adesanya TM, Zhang L, Xie N, Chen Z, Fu M, Zhang J, Zhang J, Tan T, Kilic A, Li Z, Zhu H, Xie X. Delivery of placentaderived mesenchymal stem cells ameliorates ischemia-induced limb injury by immunomodulation. Cell Physiol Biochem. 2014;34(6): Adesanya TM, Sullivan RC, Stawicki SP, Evans DC. Nutrition in Traumatic Brain Injury: Focus on the Immune Modulating Supplements. In F. Sadaka (Ed.), Traumatic Brain Injury. ISBN: Yun Y, Adesanya TM, Mitra RD. A systemic study of gene expression variation at single-nucleotide resolution reveals widespread regulatory roles for uaugs. Genome Res Jun;22(6): AWARDS AND HONORS 2016 Biophysical Society Committee for Inclusion and Diversity Travel Award; Biophysical Society 2015 Keystone Symposia/Annual Biomedical Research Conference for Minority Students Travel Award; Keystone Symposia 2015 Sigma Xi Membership; Sigma Xi: The Scientific Research Society 2014 TL1 Mentored Clinical Research Training Program Award (National Institutes of Health Award Number TL1TR001069); Center for Clinical and Translational Science, The Ohio State University 2014 American Medical Association Foundation Seed Grant Research Program Award; American Medical Association Foundation 2013 American Heart Association Basic Cardiovascular Sciences Minority Travel Grant; American Heart Association 2013 Third Place (out of 54) in the Pre-doctoral Section at the Dorothy M. Davis Heart and Lung Research Institute Research Day; The Ohio State University 2013 Physiology Training Program Fellowship; College of Medicine, The Ohio State University 2013 The Albert Schweitzer Fellowship (Doctors in Science; The Albert Schweitzer Fellowship 2012 Association for Academic Surgery Student Travel Grant; Association for Academic Surgery

8 2010 Carolyn L. Kuckein Student Research Fellowship Award (Awarded); Alpha Omega Alpha 2007 Award for the Best Oral Presentation in the Molecular Biological Sciences Section; Annual Biomedical Research Conference for Minority Students FUTURE PLANS I will be returning to medical school as a fourth-year medical student. I plan to practice as a physician-scientist, contributing to the growth of medicine and science and serving the underserved populations from which I have grown.

9 [This must be the first line on Page 9] Biomedical Sciences Graduate Program 1170 Graves Hall 333 W. 10 th Avenue Columbus, Ohio 43210