Eric M. Small
Assistant Professor, Department of Medicine, Aab Cardiovascular Research Insititute (CVRI)
|2003 | Ph.D. | University of Texas-Austin|
|1995 | BS | Cell and Molecular Biology | University of Michigan|
Research in the Small Lab is focused on understanding the molecular mechanisms that control how a cell responds to its surroundings during development or following tissue injury. Specifically, we are interested in characterizing the gene regulatory circuits that are activated following cardiac injury, and how these circuits define a cellular response.
To this end, we have three general projects based on the regulation of gene expression during tissue injury or remodeling. These projects utilize experimental approaches ranging from biochemical analyses, to cell biology, to mouse genetics and disease models. It is hoped that the insight gained from the following projects might lead to novel therapeutic strategies for the prevention or treatment of human disease.
1. Origin and contribution of activated fibroblasts during wound healing.
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. However, the cellular source and phenotypic potential of myofibroblasts is currently a source of controversy. Ongoing research in my lab is directed towards identifying the origin of these contractile fibroblasts in the heart and other tissues, and understanding the factors involved in their differentiation into myofibroblasts or other lineages following injury.
2. Transcriptional regulation of myofibroblast differentiation and tissue remodeling.
Myocardin-related transcription factors (MRTFs) are broadly expressed signal responsive transcriptional co-factor for serum response factor (SRF) that shuttle to the nucleus in response to various biomechanical or humoral signals. I have recently discovered an important role of MRTF-A during myofibroblast differentiation and scar formation following myocardial infarction (Small et al., Circ. Res 107(2);294-304; Parmacek, Circ Res 107(2):168-70). My lab is currently studying the mechanisms controlling MRTF activation during development or following injury, and evaluating their role in tissue remodeling.
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 or genetic modifiers of MRTF activity and myofibroblast differentiation using cell biology and mouse models of wound healing.
3. Regulation of cardiovascular remodeling by microRNAs.
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 (Small and Olson, Nature 469(7330):336-342.; Small et al., PNAS 197(9):4218-23;. Small et al., Circ. Res 107(11):1336-44; Xin, Small et al., Genes & Development 23(18): 2166-78). 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 project is to discover novel cooperative interactions between seemingly unrelated microRNAs via regulation of common mRNAs or physiological pathways.
NOTICE: The lab is currently accepting rotation students to pursue a variety of projects regarding transcriptional regulation and tissue remodeling
- Small EM, Olson EN. "Pervasive roles of microRNAs in cardiovascular biology." Nature. 2011; 469(7330):336-42.
- Miano JM, Small EM. "MicroRNA133a: a new variable in vascular smooth muscle cell phenotypic switching." Circulation research. 2011; 109(8):825-7.
- 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." Proceedings of the National Academy of Sciences of the United States of America. 2010; 107(9):4218-23. Epub 2010 Feb 08.
- Small EM, Frost RJ, Olson EN. "MicroRNAs add a new dimension to cardiovascular disease." Circulation. 2010; 121(8):1022-32.
- 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." Circulation research. 2010; 107(2):294-304. Epub 2010 Jun 17.
Eric Small , Ph.D.
University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box CVRI
Rochester, New York 14642
Admin. Office: (585) 276-9800