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Eric M. Small, Ph.D.

Contact Information

Phone Numbers

Administrative: (585) 276-7698

Office: (585) 276-7706

Fax: (585) 276-1530

Faculty Appointments

Biography

Professional Background

Dr. Small earned his undergraduate degree from the University of Michigan in 1995. He then completed a Ph.D. in the laboratory of Dr. Paul Krieg at the University of Texas at Austin in 2003, where he defined transcriptional mechanisms that regulate the early stages of heart development. During subsequent post-doctoral training under Dr. Eric Olson at UTSW Medical Center at Dallas, he made contributions towards understanding the transcriptional mechanisms regulating cardiovascular development and remodeling using a combination of cell biological techniques and mouse genetics. Dr. Small was recruited to the University of Rochester Medical Center in 2011. His general research interests focus on understanding how a cell can interpret biomechanical and humoral signals and activate a discrete transcriptional program during development or in response to injury.

Research

Research in the Small Lab is focused on understanding the molecular mechanisms that govern how a cell responds to its surroundings during development or following tissue injury. Specifically, we are interested in defining the gene regulatory circuits that are activated following cardiac injury, and how these circuits define a cellular response. To this end, we have three main projects based on gene regulation studies during tissue injury or remodeling:

1. One major component of wound healing, in dermal wounds or a damaged organ alike, is the proliferation and activation of fibroblasts, called "myofibroblasts". Activated myofibroblasts are contractile cells that promote wound closure due in part to the expression of smooth muscle contractile proteins and the deposition of high levels of extracellular matrix. My lab is dedicated to identifying the cellular source of these contractile fibroblasts in the heart and understanding the factors involved in their differentiation following injury.

2. Myocardin-related transcription factor (MRTF)-A is a ubiquitously expressed signal responsive transcriptional co-factor for serum response factor (SRF) that moves to the nucleus in response to various cues that promote F-actin polymerization. I have recently discovered an important role of MRTF-A during myofibroblast differentiation and scar formation following myocardial infarction. My lab is currently studying the mechanisms controlling MRTF activation during development or following cardiac injury, and identifying novel partners in these processes. MRTFs and myofibroblast differentiation are also intriguing therapeutic targets for the prevention or treatment of diseases characterized by inappropriate contractility or scar formation. Therefore, in an extension of this project, we are pursuing novel small molecule modifiers of MRTF activity and myofibroblast differentiation using cell biology and mouse models of wound healing.

3. I have recently identified a number of microRNAs that are activated by SRF and MRTF-A, some of which play a role in cardiovascular remodeling. We are interested in defining the importance of post-transcriptional regulation of gene expression by these microRNAs in tissue homeostasis. The main goal of this aim would be to discover novel cooperative interactions between seemingly unrelated microRNAs via regulation of common mRNAs or physiological pathways.

These projects utilize experimental approaches ranging from biochemical analyses, to cell biology, to mouse models of disease. It is hoped that the insight gained from answering these basic biological questions might lead to novel therapeutic strategies for the prevention or treatment of human disease.

Credentials

Education

1995
BS | University of Michigan
Cell and Molecular Biology

2003
PhD | Univ Texas-Austin
Molecular Biology

Post-doctoral Training & Residency

0 - 2005
Hospital for Sick Children, Toronto, ON (Mentor: Benoit Bruneau)

0 - 2009
UT Southwestern Medical Center at Dallas, Dallas, TX (Mentor: Eric N. Olson)

Awards

2013
Excellence in Postdoctoral Mentoring Award

2010 - 2014
Scientist Development Grant
Sponsor: American Heart Association

2004 - 2007
Ruth L. Kirschstein NRSA Post-Doctoral Fellowship
Sponsor: National Institutes of Health

2002
Best Poster Presentation Award
Sponsor: Weinstein Cardiovascular Conference

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Publications

Journal Articles

10/23/2018
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. "Mechanosensitive Gene Regulation by Myocardin-Related Transcription Factors Is Required for Cardiomyocyte Integrity in Load-Induced Ventricular Hypertrophy." Circulation.. 2018 Oct 23; 138(17):1864-1878.

4/10/2018
Burke RM, Lighthouse JK, Quijada P, Dirkx RA, Rosenberg A, Moravec CS, Alexis JD, Small EM. "Small proline-rich protein 2B drives stress-dependent p53 degradation and fibroblast proliferation in heart failure." Proceedings of the National Academy of Sciences of the United States of America.. 2018 Apr 10; 115(15):E3436-E3445. Epub 2018 Mar 26.

2/2018
Guo B, Lyu Q, Slivano OJ, Dirkx R, Christie CK, Czyzyk J, Hezel AF, Gharavi AG, Small EM, Miano JM. "Serum Response Factor Is Essential for Maintenance of Podocyte Structure and Function." Journal of the American Society of Nephrology : JASN.. 2018 Feb 0; 29(2):416-422. Epub 2017 Nov 07.

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