Miano Lab
Joseph M. Miano
Associate Director - Aab Cardiovascular Research Institute |
|
| Associate Professor - Department of Medicine, Aab Cardiovascular Research Institute | |
| 1992 | Ph.D. | Experimental Pathology | New York Medical College | |
| 1988 | M.S. | Experimental Pathology | New York Medical College | |
| 1986 | B.S. | Biology | SUNY College at Cortland |
Research Overview
Our lab is committed to understanding as much as we can about the genes that define a functionally differentiated smooth muscle cell (SMC) phenotype. Normal SMC differentiation is defined by expression of several genes (A, in Figure below), including the SRF-Myocardin switch that we first reported to be important in turning on SMC genes in a non-SMC type. A variety of disease processes are closely associated with the reduction or complete loss in SMC differentiation gene expression which typifies a less differentiated (so-called synthetic) SMC (B). The vascular diseases where such phenotypic adaptations occur include those that reduce luminal area (C) such as atherosclerosis or neointimal lesion formation following organ transplantation. We are also interested in diseases where SMC differentiation genes may be over-expressed resulting in exaggerated SMC contractile gene expression as seen in Alzheimer’s disease or asthma. One of the main areas of interest is elucidating the transcriptional and post-transcriptional control of SMC differentiation genes using mouse models. Our transgenic mouse models of SMC gene promoters encompass conventional transgenic approaches using the bacterial lacZ reporter gene or large genomic sequences contained in bacterial artificial chromosomes (BACs) (D). We also design and carry out knockout studies in mice to define regulatory element activity or to inactivate a gene’s function to assess its physiological importance during embryonic and postnatal development (E). Defining the activity of SMC gene promoters in vivo provides an opportunity to define DNA sequence elements that are critical for such regulation. We use a variety of bioinformatic tools to define DNA sequences that may be critical for SMC gene activity (F). One major initiative is what we call the Human CArGome Project (G) whose charge is to elucidate all functional SRF-binding CArG boxes in the genome and to pinpoint variants (e.g., SNPs) that may alter SRF binding and target gene expression leading to disease phenotypes. The CArGome Project has resulted in new SRF-Myocardin target genes (H) that we are then able to feed back into the pipeline for further analysis. Our approaches therefore span the gamut from pathology model systems to mouse genetics, computational biology, and state-of-the-art molecular biology. Our long-term goal is to gain a complete understanding of the transcriptional and post-transcriptional processes underlying vascular SMC differentiation during development and in disease processes.
Projects
Recent Publications
- Leiomodin1: A new serum response factor-dependent target gene expressed preferentially in differentiated smooth muscle cells., Nanda V, Miano JM., J Biol Chem. 2011 Dec 7.
- MicroRNA133a: a new variable in vascular smooth muscle cell phenotypic switching., Miano JM, Small EM., Circ Res. 2011 Sep 30;109(8):825-7.
- Smooth muscle calponin: an unconventional CArG-dependent gene that antagonizes neointimal formation. Long X, Slivano OJ, Cowan SL, Georger MA, Lee TH, Miano JM., Arterioscler Thromb Vasc Biol. 2011 Oct;31(10):2172-80.
- Identifying functional single nucleotide polymorphisms in the human CArGome. Benson CC, Zhou Q, Long X, Miano JM., Physiol Genomics. 2011 Sep 22;43(18):1038-48
- Transforming growth factor-beta1 (TGF-beta1) utilizes distinct pathways for the transcriptional activation of microRNA 143/145 in human coronary artery smooth muscle cells., Long X, Miano JM., J Biol Chem. 2011 Aug 26;286(34):30119-29.
More papers:
Miano's Suggested Links
Contact
Joseph Miano , PhD
University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box CVRI
Rochester, New York 14642
email
Lab Members
 |
Craig C. Benson |
 |
Postdoctoral Research Associate |
 |
Lab Technician |
 |
Research Assistant Professor |
 |
Graduate Student |
 |
Lab Technician |
 |
Research Assistant Professor |
| Former Lab Members | |
