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Eric Small

TitleAssistant Professor
InstitutionSchool of Medicine and Dentistry
DepartmentMedicine in the Aab Cardiovascular Research Institute
AddressAab Cardiovascular Research Institute
211 Bailey Road
West Henrietta NY 14586
Other Positions
TitleAssistant Professor
InstitutionSchool of Medicine and Dentistry
DepartmentPharmacology and Physiology

 
 Awards And Honors
2002     Best Poster Presentation Award  | Weinstein Cardiovascular Conference
2004 - 2007Ruth L. Kirschstein NRSA Post-Doctoral Fellowship  | National Institutes of Health
2010 - 2014Scientist Development Grant  | American Heart Association
 
 Overview
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.

 
 Selected Publications
List All   |   Timeline
  1. Velasquez LS, Sutherland LB, Liu Z, Grinnell F, Kamm KE, Schneider JW, Olson EN, Small EM. Activation of MRTF-A-dependent gene expression with a small molecule promotes myofibroblast differentiation and wound healing. Proc Natl Acad Sci U S A. 2013 Oct 15; 110(42):16850-5.
    View in: PubMed
  2. Rodés-Cabau J, Dauerman HL, Cohen MG, Mehran R, Small EM, Smyth SS, Costa MA, Mega JL, O'Donoghue ML, Ohman EM, Becker RC. Antithrombotic treatment in transcatheter aortic valve implantation: insights for cerebrovascular and bleeding events. J Am Coll Cardiol. 2013 Dec 24; 62(25):2349-59.
    View in: PubMed
  3. Small EM. The Actin-MRTF-SRF Gene Regulatory Axis and Myofibroblast Differentiation. J Cardiovasc Transl Res. 2012 Dec; 5(6):794-804.
    View in: PubMed
  4. Miano JM, Small EM. MicroRNA133a: a new variable in vascular smooth muscle cell phenotypic switching. Circ Res. 2011 Sep 30; 109(8):825-7.
    View in: PubMed
  5. Small EM, Olson EN. Pervasive roles of microRNAs in cardiovascular biology. Nature. 2011 Jan 20; 469(7330):336-42.
    View in: PubMed
  6. Small EM, Sutherland LB, Rajagopalan KN, Wang S, Olson EN. MicroRNA-218 regulates vascular patterning by modulation of Slit-Robo signaling. Circ Res. 2010 Nov 26; 107(11):1336-44.
    View in: PubMed
  7. Small EM, Thatcher JE, Sutherland LB, Kinoshita H, Gerard RD, Richardson JA, Dimaio JM, Sadek H, Kuwahara K, Olson EN. Myocardin-related transcription factor-a controls myofibroblast activation and fibrosis in response to myocardial infarction. Circ Res. 2010 Jul 23; 107(2):294-304.
    View in: PubMed
  8. Small EM, Frost RJ, Olson EN. MicroRNAs add a new dimension to cardiovascular disease. Circulation. 2010 Mar 2; 121(8):1022-32.
    View in: PubMed
  9. Small EM, O'Rourke JR, Moresi V, Sutherland LB, McAnally J, Gerard RD, Richardson JA, Olson EN. Regulation of PI3-kinase/Akt signaling by muscle-enriched microRNA-486. Proc Natl Acad Sci U S A. 2010 Mar 2; 107(9):4218-23.
    View in: PubMed
  10. Xin M, Small EM, Sutherland LB, Qi X, McAnally J, Plato CF, Richardson JA, Bassel-Duby R, Olson EN. MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. Genes Dev. 2009 Sep 15; 23(18):2166-78.
    View in: PubMed
  11. Meadows SM, Warkman AS, Salanga MC, Small EM, Krieg PA. The myocardin-related transcription factor, MASTR, cooperates with MyoD to activate skeletal muscle gene expression. Proc Natl Acad Sci U S A. 2008 Feb 5; 105(5):1545-50.
    View in: PubMed
  12. Xin M, Small EM, van Rooij E, Qi X, Richardson JA, Srivastava D, Nakagawa O, Olson EN. Essential roles of the bHLH transcription factor Hrt2 in repression of atrial gene expression and maintenance of postnatal cardiac function. Proc Natl Acad Sci U S A. 2007 May 8; 104(19):7975-80.
    View in: PubMed
  13. Small EM, Warkman AS, Wang DZ, Sutherland LB, Olson EN, Krieg PA. Myocardin is sufficient and necessary for cardiac gene expression in Xenopus. Development. 2005 Mar; 132(5):987-97.
    View in: PubMed
  14. Small EM, Krieg PA. Molecular regulation of cardiac chamber-specific gene expression. Trends Cardiovasc Med. 2004 Jan; 14(1):13-8.
    View in: PubMed
  15. Small EM, Krieg PA. Transgenic analysis of the atrialnatriuretic factor (ANF) promoter: Nkx2-5 and GATA-4 binding sites are required for atrial specific expression of ANF. Dev Biol. 2003 Sep 1; 261(1):116-31.
    View in: PubMed
  16. Small EM, Krieg PA. Molecular mechanisms of chamber-specific myocardial gene expression: transgenic analysis of the ANF promoter. Cold Spring Harb Symp Quant Biol. 2002; 67:71-9.
    View in: PubMed
  17. Wang D, Passier R, Liu ZP, Shin CH, Wang Z, Li S, Sutherland LB, Small E, Krieg PA, Olson EN. Regulation of cardiac growth and development by SRF and its cofactors. Cold Spring Harb Symp Quant Biol. 2002; 67:97-105.
    View in: PubMed
  18. Wang D, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, Krieg PA, Olson EN. Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor. Cell. 2001 Jun 29; 105(7):851-62.
    View in: PubMed
  19. Garriock RJ, Vokes SA, Small EM, Larson R, Krieg PA. Developmental expression of the Xenopus Iroquois-family homeobox genes, Irx4 and Irx5. Dev Genes Evol. 2001 May; 211(5):257-60.
    View in: PubMed
  20. Small EM, Krieg PA. Expression of atrial natriuretic factor (ANF) during Xenopus cardiac development. Dev Genes Evol. 2000 Dec; 210(12):638-40.
    View in: PubMed
  21. Small EM, Vokes SA, Garriock RJ, Li D, Krieg PA. Developmental expression of the Xenopus Nkx2-1 and Nkx2-4 genes. Mech Dev. 2000 Sep; 96(2):259-62.
    View in: PubMed

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