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Eric M. Small, Ph.D.

Eric M. Small, Ph.D.

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About Me

Dr. Eric Small earned his B.S. degree in Cellular and Molecular Biology from the University of Michigan. He then completed a Ph.D. in the laboratory of Dr. Paul Krieg at the University of Texas at Austin, where he defined transcriptional mechanisms that regulate the early stages of heart development...
Dr. Eric Small earned his B.S. degree in Cellular and Molecular Biology from the University of Michigan. He then completed a Ph.D. in the laboratory of Dr. Paul Krieg at the University of Texas at Austin, where he defined transcriptional mechanisms that regulate the early stages of heart development. During subsequent post-doctoral training in Dr. Eric Olson's lab at UT Southwestern Medical Center at Dallas, he studied transcriptional and post-transcriptional mechanisms regulating gene expression in embryonic development and pathological cardiac remodeling. Dr. Small was recruited to the University of Rochester Medical Center in 2011. He is currently Associate Professor of Medicine at the Aab Cardiovascular Research Institute, with secondary appointments in Pharmacology and Physiology and Biomedical Engineering. Current research in the Small Lab focuses on defining mechanisms that control cardiac fibroblast plasticity and the development of pathological cardiac fibrosis.

Faculty Appointments

Associate Professor - Department of Medicine, Aab Cardiovascular Research Institute (SMD)

Associate Professor - Department of Biomedical Engineering (SMD) - Joint

Associate Professor - Department of Pharmacology and Physiology (SMD) - Joint

Credentials

Post-doctoral Training & Residency

UT Southwestern Medical Center at Dallas, Dallas, TX (Mentor: Eric N. Olson) 2005 - 2011

Hospital for Sick Children, Toronto, ON (Mentor: Benoit Bruneau) 2004 - 2005

Education

PhD | Univ Texas-Austin. Molecular Biology. 2003

BS | University of Michigan. Cell and Molecular Biology. 1995

Awards

Established Investigator Award. 2023

Excellence in Postdoctoral Mentoring Award. 2013

Scientist Development Grant. 2010 - 2014

Ruth L. Kirschstein NRSA Post-Doctoral Fellowship. 2004 - 2007

Best Poster Presentation Award. 2002

Research

The overall goal of the Small lab is to better understand the mechanisms that control cell identity and lineage commitment by studying the transcriptional regulation and function of cardiac tissue-restricted genes. Our motivation is to decipher how disruption of cardiac gene expression programs in h...
The overall goal of the Small lab is to better understand the mechanisms that control cell identity and lineage commitment by studying the transcriptional regulation and function of cardiac tissue-restricted genes. Our motivation is to decipher how disruption of cardiac gene expression programs in heart disease contributes to cellular pathophysiology and the decline in cardiac function. There are two major themes of research within the lab that we study using mouse genetics, cell biology, advanced imaging, bioinformatic and biochemical approaches:

1. Cardiac fibroblast plasticity and the development of cardiac fibrosis. The transition to heart failure following cardiac insult is the result of irreversible cardiomyocyte loss and the development of cardiac fibrosis, which impedes contractility and can initiate lethal arrhythmias. Cardiac fibrosis arises from the aberrant and persistent stimulation of fibroblasts, the main source of extracellular matrix in the heart, in a pathological attempt to repair damaged tissue. We utilize gene expression profiling in animal models of heart disease and human heart failure patient samples to identify novel regulators of cardiac fibroblast accumulation and myofibroblast activation in health and disease. We also utilize high-throughput screening and pre-clinical animal studies to develop novel pharmacological and gene-targeting strategies to block or reverse cardiac scarring and the progression of heart failure.

2. Epicardium-derived progenitor cell mobilization. Epicardium-derived progenitor cells (EPDCs) can differentiate into cardiac fibroblasts and coronary blood vessels, and secrete signals that stimulate cardiac growth during embryonic development. We are striving to understand how EPDCs interpret developmental signals and differentiate into the appropriate cell type based upon their location within the heart. We have identified a mechanosensitive gene program that is essential for EPDC migration and subsequent differentiation into fibroblasts and perivascular cells. Ongoing studies are aimed at evaluating whether disruption of mechanosensitive transcriptional programs within the epicardium might contribute to cardiomyopathy. Our long-term goal is to harness the regenerative potential of the epicardium to improve cardiac repair.

Publications

Journal Articles

P53 Regulates the Extent of Fibroblast Proliferation and Fibrosis in Left Ventricle Pressure Overload.

Liu X, Burke RM, Lighthouse JK, Baker CD, Dirkx RA, Kang B, Chakraborty Y, Mickelsen DM, Twardowski J, Mello SS, Ashton JM, Small EM

Circulation research.. 2023 July 6 Epub 07/06/2023.

Cardiac pericytes mediate the remodeling response to myocardial infarction.

Quijada P, Park S, Zhao P, Kolluri KS, Wong D, Shih KD, Fang K, Pezhouman A, Wang L, Daraei A, Tran MD, Rathbun EM, Burgos Villar KN, Garcia-Hernandez ML, Pham TT, Lowenstein CJ, Iruela-Arispe ML, Carmichael ST, Small EM, Ardehali R

The Journal of clinical investigation.. 2023 May 15133 (10)Epub 05/15/2023.

Cell-Based Phenotypic Screen for Antifibrotic Compounds Targets Eicosanoid Metabolism.

Lighthouse JK, Small EM

Circulation research.. 2023 January 6132 (1):30-33. Epub 01/05/2023.

SIRT6 Mitigates Heart Failure With Preserved Ejection Fraction in Diabetes.

Wu X, Liu H, Brooks A, Xu S, Luo J, Steiner R, Mickelsen DM, Moravec CS, Jeffrey AD, Small EM, Jin ZG

Circulation research.. 2022 October 24 Epub 10/24/2022.

Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of ARVC.

Pérez-Hernández M, van Opbergen CJM, Bagwan N, Rasmus Vissing C, Marrón-Liñares GM, Zhang M, Torres Vega E, Sorrentino A, Drici L, Sulek K, Zhai R, Hansen FB, Hørby Christensen A, Boesgaard S, Gustafsson F, Rossing K, Small EM, Davies MJ, Rothenberg E, Sato P, Cerrone M, Jensen THL, Qvortrup K, Bundgaard H, Delmar M, Lundby A

Circulation.. 2022 August 12 :101161CIRCULATIONAHA122060454. Epub 08/12/2022.

Transcriptional regulation of cardiac fibroblast phenotypic plasticity.

Burgos Villar KN, Liu X, Small EM

Current opinion in physiology.. 2022 August 28 Epub 06/03/2022.

Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics.

Misra A, Baker CD, Pritchett EM, Burgos Villar KN, Ashton JM, Small EM

Journal of cardiovascular development and disease.. 2021 December 219 (1)Epub 12/21/2021.

Coordination of endothelial cell positioning and fate specification by the epicardium.

Quijada P, Trembley MA, Misra A, Myers JA, Baker CD, Pérez-Hernández M, Myers JR, Dirkx RA, Cohen ED, Delmar M, Ashton JM, Small EM

Nature communications.. 2021 July 612 (1):4155. Epub 07/06/2021.

Prevention of Fibrosis and Pathological Cardiac Remodeling by Salinomycin.

Burke RM, Dirkx RA, Quijada P, Lighthouse JK, Mohan A, O'Brien M, Wojciechowski W, Woeller C, Phipps RP, Alexis JD, Ashton J, Small EM

Circulation research.. 2021 April 7 Epub 04/07/2021.

Sarcomeres regulate murine cardiomyocyte maturation through MRTF-SRF signaling.

Guo Y, Cao Y, Jardin BD, Sethi I, Ma Q, Moghadaszadeh B, Troiano EC, Mazumdar N, Trembley MA, Small EM, Yuan GC, Beggs AH, Pu WT

Proceedings of the National Academy of Sciences of the United States of America.. 2021 January 12118 (2)Epub 1900 01 01.

Fibroblast contributions to ischemic cardiac remodeling.

Burke RM, Burgos Villar KN, Small EM

Cellular signalling.. 2020 October 31 :109824. Epub 10/31/2020.

Cut the YAP: Limiting Fibrosis in Pathologic Cardiac Remodeling.

Small EM, Brooks AC

JACC. Basic to translational science.. 2020 September 5 (9):946-948. Epub 09/28/2020.

The Role of the Epicardium During Heart Development and Repair.

Quijada P, Trembley MA, Small EM

Circulation research.. 2020 January 31126 (3):377-394. Epub 01/30/2020.

A Novel Role of Cyclic Nucleotide Phosphodiesterase 10A in Pathological Cardiac Remodeling and Dysfunction.

Chen S, Zhang Y, Lighthouse JK, Mickelsen DM, Wu J, Yao P, Small EM, Yan C

Circulation.. 2019 December 5 Epub 12/05/2019.

Myofibroblast-specific YY1 promotes liver fibrosis.

Liu H, Zhang S, Xu S, Koroleva M, Small EM, Jin ZG

Biochemical and biophysical research communications.. 2019 June 30514 (3):913-918. Epub 05/10/2019.

Sacubitril/Valsartan Decreases Cardiac Fibrosis in Left Ventricle Pressure Overload by Restoring PKG Signaling in Cardiac Fibroblasts.

Burke RM, Lighthouse JK, Mickelsen DM, Small EM

Circulation. Heart failure.. 2019 April 12 (4):e005565. Epub 1900 01 01.

Platelet-derived ?2M regulates monocyte inflammatory responses.

Hilt ZT, Pariser DN, Ture SK, Mohan A, Quijada P, Asante A, Cameron SJ, Sterling JA, Merkel AR, Johanson AL, Jenkins JL, Small EM, McGrath KE, Palis J, Elliott MR, Morrell CN

JCI insight.. 2019 March 74 (5)Epub 03/07/2019.

Activated Human Lung Fibroblasts Produce Extracellular Vesicles with Antifibrotic Prostaglandins.

Lacy SH, Woeller CF, Thatcher TH, Pollock SJ, Small EM, Sime PJ, Phipps RP

American journal of respiratory cell and molecular biology.. 2019 March 60 (3):269-278. Epub 1900 01 01.

Pre-existing fibroblasts of epicardial origin are the primary source of pathological fibrosis in cardiac ischemia and aging.

Quijada P, Misra A, Velasquez LS, Burke RM, Lighthouse JK, Mickelsen DM, Dirkx RA, Small EM

Journal of molecular and cellular cardiology.. 2019 February 13129 :92-104. Epub 02/13/2019.

Exercise promotes a cardioprotective gene program in resident cardiac fibroblasts.

Lighthouse JK, Burke RM, Velasquez LS, Dirkx RA, Aiezza A, Moravec CS, Alexis JD, Rosenberg A, Small EM

JCI insight.. 2019 January 104 (1)Epub 01/10/2019.

LAMP-2B regulates human cardiomyocyte function by mediating autophagosome-lysosome fusion.

Chi C, Leonard A, Knight WE, Beussman KM, Zhao Y, Cao Y, Londono P, Aune E, Trembley MA, Small EM, Jeong MY, Walker LA, Xu H, Sniadecki NJ, Taylor MR, Buttrick PM, Song K

Proceedings of the National Academy of Sciences of the United States of America.. 2019 January 8116 (2):556-565. Epub 12/24/2018.

Mechanosensitive Gene Regulation by Myocardin-Related Transcription Factors Is Required for Cardiomyocyte Integrity in Load-Induced Ventricular Hypertrophy.

Trembley MA, Quijada P, Agullo-Pascual E, Tylock KM, Colpan M, Dirkx RA, Myers JR, Mickelsen DM, de Mesy Bentley K, Rothenberg E, Moravec CS, Alexis JD, Gregorio CC, Dirksen RT, Delmar M, Small EM

Circulation.. 2018 October 23138 (17):1864-1878. Epub 1900 01 01.

Small proline-rich protein 2B drives stress-dependent p53 degradation and fibroblast proliferation in heart failure.

Burke RM, Lighthouse JK, Quijada P, Dirkx RA, Rosenberg A, Moravec CS, Alexis JD, Small EM

Proceedings of the National Academy of Sciences of the United States of America.. 2018 April 10115 (15):E3436-E3445. Epub 03/26/2018.

Serum Response Factor Is Essential for Maintenance of Podocyte Structure and Function.

Guo B, Lyu Q, Slivano OJ, Dirkx R, Christie CK, Czyzyk J, Hezel AF, Gharavi AG, Small EM, Miano JM

Journal of the American Society of Nephrology : JASN.. 2018 February 29 (2):416-422. Epub 11/07/2017.

Tension Creates an Endoreplication Wavefront that Leads Regeneration of Epicardial Tissue.

Cao J, Wang J, Jackman CP, Cox AH, Trembley MA, Balowski JJ, Cox BD, De Simone A, Dickson AL, Di Talia S, Small EM, Kiehart DP, Bursac N, Poss KD

Developmental cell.. 2017 September 2542 (6):600-615.e4. Epub 1900 01 01.

?-Adrenergic Blockade in Ischemia-Reperfusion Injury: ?ARKing Up a New Tree.

Small EM, Burke RM

Journal of the American College of Cardiology.. 2017 August 2270 (8):972-974. Epub 1900 01 01.

PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction.

Knight WE, Chen S, Zhang Y, Oikawa M, Wu M, Zhou Q, Miller CL, Cai Y, Mickelsen DM, Moravec C, Small EM, Abe J, Yan C

Proceedings of the National Academy of Sciences of the United States of America.. 2016 November 8113 (45):E7116-E7125. Epub 10/20/2016.

Epicardial Outgrowth Culture Assay and Ex Vivo Assessment of Epicardial-derived Cell Migration.

Trembley MA, Velasquez LS, Small EM

Journal of visualized experiments : JoVE.. 2016 March 18 (109)Epub 03/18/2016.

Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis.

Luna-Zurita L, Stirnimann CU, Glatt S, Kaynak BL, Thomas S, Baudin F, Samee MA, He D, Small EM, Mileikovsky M, Nagy A, Holloway AK, Pollard KS, Müller CW, Bruneau BG

Cell.. 2016 February 25164 (5):999-1014. Epub 02/11/2016.

Transcriptional control of cardiac fibroblast plasticity.

Lighthouse JK, Small EM

Journal of molecular and cellular cardiology.. 2016 February 91 :52-60. Epub 12/22/2015.

Myocardin-related transcription factors control the motility of epicardium-derived cells and the maturation of coronary vessels.

Trembley MA, Velasquez LS, de Mesy Bentley KL, Small EM

Development.. 2015 January 1142 (1):21-30. Epub 1900 01 01.

Antithrombotic treatment in transcatheter aortic valve implantation: insights for cerebrovascular and bleeding events.

Rodés-Cabau J, Dauerman HL, Cohen MG, Mehran R, Small EM, Smyth SS, Costa MA, Mega JL, O'Donoghue ML, Ohman EM, Becker RC

Journal of the American College of Cardiology.. 2013 December 2462 (25):2349-2359. Epub 04/10/2013.

Activation of MRTF-A-dependent gene expression with a small molecule promotes myofibroblast differentiation and wound healing.

Velasquez LS, Sutherland LB, Liu Z, Grinnell F, Kamm KE, Schneider JW, Olson EN, Small EM

Proceedings of the National Academy of Sciences of the United States of America.. 2013 October 15110 (42):16850-5. Epub 09/30/2013.

The actin-MRTF-SRF gene regulatory axis and myofibroblast differentiation.

Small EM

Journal of cardiovascular translational research.. 2012 December 5 (6):794-804. Epub 08/17/2012.

MicroRNA133a: a new variable in vascular smooth muscle cell phenotypic switching.

Miano JM, Small EM

Circulation research.. 2011 September 30109 (8):825-7. Epub 1900 01 01.

Pervasive roles of microRNAs in cardiovascular biology.

Small EM, Olson EN

Nature.. 2011 January 20469 (7330):336-42. Epub 1900 01 01.

MicroRNA-218 regulates vascular patterning by modulation of Slit-Robo signaling.

Small EM, Sutherland LB, Rajagopalan KN, Wang S, Olson EN

Circulation research.. 2010 November 26107 (11):1336-44. Epub 10/14/2010.

Myocardin-related transcription factor-a controls myofibroblast activation and fibrosis in response to myocardial infarction.

Small EM, Thatcher JE, Sutherland LB, Kinoshita H, Gerard RD, Richardson JA, Dimaio JM, Sadek H, Kuwahara K, Olson EN

Circulation research.. 2010 July 23107 (2):294-304. Epub 06/17/2010.

Regulation of PI3-kinase/Akt signaling by muscle-enriched microRNA-486.

Small EM, O'Rourke JR, Moresi V, Sutherland LB, McAnally J, Gerard RD, Richardson JA, Olson EN

Proceedings of the National Academy of Sciences of the United States of America.. 2010 March 2107 (9):4218-23. Epub 02/08/2010.

MicroRNAs add a new dimension to cardiovascular disease.

Small EM, Frost RJ, Olson EN

Circulation.. 2010 March 2121 (8):1022-32. Epub 1900 01 01.

MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury.

Xin M, Small EM, Sutherland LB, Qi X, McAnally J, Plato CF, Richardson JA, Bassel-Duby R, Olson EN

Genes & development.. 2009 September 1523 (18):2166-78. Epub 08/31/2009.

The myocardin-related transcription factor, MASTR, cooperates with MyoD to activate skeletal muscle gene expression.

Meadows SM, Warkman AS, Salanga MC, Small EM, Krieg PA

Proceedings of the National Academy of Sciences of the United States of America.. 2008 February 5105 (5):1545-50. Epub 01/29/2008.

Essential roles of the bHLH transcription factor Hrt2 in repression of atrial gene expression and maintenance of postnatal cardiac function.

Xin M, Small EM, van Rooij E, Qi X, Richardson JA, Srivastava D, Nakagawa O, Olson EN

Proceedings of the National Academy of Sciences of the United States of America.. 2007 May 8104 (19):7975-80. Epub 04/27/2007.

Myocardin is sufficient and necessary for cardiac gene expression in Xenopus.

Small EM, Warkman AS, Wang DZ, Sutherland LB, Olson EN, Krieg PA

Development.. 2005 March 132 (5):987-97. Epub 01/26/2005.

Molecular regulation of cardiac chamber-specific gene expression.

Small EM, Krieg PA

Trends in cardiovascular medicine.. 2004 January 14 (1):13-8. Epub 1900 01 01.

Molecular mechanisms of chamber-specific myocardial gene expression: transgenic analysis of the ANF promoter.

Small EM, Krieg PA

Cold Spring Harbor symposia on quantitative biology.. 2002 67 :71-9. Epub 1900 01 01.

Regulation of cardiac growth and development by SRF and its cofactors.

Wang D, Passier R, Liu ZP, Shin CH, Wang Z, Li S, Sutherland LB, Small E, Krieg PA, Olson EN

Cold Spring Harbor symposia on quantitative biology.. 2002 67 :97-105. Epub 1900 01 01.

Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor.

Wang D, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, Krieg PA, Olson EN

Cell.. 2001 June 29105 (7):851-62. Epub 1900 01 01.

Developmental expression of the Xenopus Iroquois-family homeobox genes, Irx4 and Irx5.

Garriock RJ, Vokes SA, Small EM, Larson R, Krieg PA

Development genes and evolution.. 2001 May 211 (5):257-60. Epub 1900 01 01.

Expression of atrial natriuretic factor (ANF) during Xenopus cardiac development.

Small EM, Krieg PA

Development genes and evolution.. 2000 December 210 (12):638-40. Epub 1900 01 01.

Developmental expression of the Xenopus Nkx2-1 and Nkx2-4 genes.

Small EM, Vokes SA, Garriock RJ, Li D, Krieg PA

Mechanisms of development.. 2000 September 96 (2):259-62. Epub 1900 01 01.