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Miano Lab

Joseph M. Miano, Ph.D.

Associate Director, Aab Cardiovascular Research Institute
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

Altered programs of cellular differentiation underlie most complex diseases. For example, smooth muscle cells (SMC) of the blood vessel wall undergo de-differentiation in various human diseases such as atherosclerosis and transplant arteriopathy. The Miano Lab utilizes tools in bioinformatics and genomics to interrogate vascular disease models (A) and cultured human coronary SMC (B) to discover novel DNA elements and genes in human/mouse genomes that impinge on the SMC differentiation program. Current funded projects include the definition of the CArGome, which is the full complement of serum response factor (SRF) binding CArG elements in human/mouse genomes, and CArG-SNPs (CArG Variome) that disrupt normal SRF binding (C); the discovery and functional analysis of new SRF/Myocardin (SRF cofactor) target genes such as AKAP12A and LMOD1 (D); and the discovery of long noncoding RNA (lncRNA) genes, such as the recently defined SENCR gene (E). LncRNA genes, which already out number all protein-coding genes and are emerging as critical mediators of cellular homeostasis, are the subject of intense study in the lab using various molecular (eg, Northern/RACE/qRT-PCR/luciferase), cell biological (RNA-FISH), biochemical (RNA pulldown), and genomic (RNA-seq/RIP-seq) assays (F). This discovery-based research culminates with in vivo functionality of CArG elements (or CArG-SNPs), protein-coding genes (AKAP12A/LMOD1) as well as lncRNA genes (G) using the revolutionary CRISPR/Cas9 genome editing system in mice. In this manner, the lab is able to rapidly (few months) assess the role of CArG boxes or various genes in an in vivo setting and in doing so develop new ways of understanding the pathogenesis of human diseases (H).

The Miano Lab’s ideas and efforts span the spectrum from computer to DNA to cells to whole animals. The lab intends to elucidate the regulation of priority genes and their functions during normal or pathological processes involving, but not limited to, the cardiovascular system. Work in the Miano Lab is necessarily multi-disciplinary and therefore provides ample opportunities for trainees to learn and utilize state-of-the-art technologies in genomics, genetics, bioinformatics, vascular pathobiology, and gene transcription control.

Miano Lab Research Pipeline (2014)

Miano Lab Figure

Recent Publications

  1. A CRISPR Path to Engineering New Genetic Mouse Models for Cardiovascular Research. Miano JM, Zhu QM, Lowenstein CJ., Arterioscler Thromb Vasc Biol. 2016 Jun;36(6):1058-75. doi 10.1161/ATVBAHA.116.304790. Epub 2016 Apr 21. PMID: 27102963

  2. Smooth Muscle Enriched Long Noncoding RNA (SMILR) Regulates Cell Proliferation., Ballantyne MD, Pinel K, Dakin R, Vesey AT, Diver L, Mackenzie R, Garcia R, Welsh P, Sattar N, Hamilton G, Joshi N, Dweck MR, Miano JM, McBride MW, Newby DE, McDonald RA, Baker AH., Circulation. 2016 May 24;133(21):2050-65. doi: 10.1161/CIRCULATIONAHA.115.021019. Epub 2016 Apr 6., PMID: 27052414

  3. A Role for the Long Noncoding RNA SENCR in Commitment and Function of Endothelial Cells., Boulberdaa M, Scott E, Ballantyne M, Garcia R, Descamps B, Angelini GD, Brittan M, Hunter A, McBride M, McClure J, Miano JM, Emanueli C, Mills NL, Mountford JC, Baker AH., Mol Ther. 2016 May;24(5):978-90. doi: 10.1038/mt.2016.41. Epub 2016 Feb 22., PMID: 26898221

  4. CRISPR-Cas9 genome editing of a single regulatory element nearly abolishes target gene expression in mice--brief report., Han Y, Slivano OJ, Christie CK, Cheng AW, Miano JM., Arteriosclerosis, thrombosis, and vascular biology. 2015 Feb; 35(2):312-5. Epub 2014 Dec 23.

  5. The short and long of noncoding sequences in the control of vascular cell phenotypes., Miano JM, Long X., Cellular and molecular life sciences : CMLS. 2015 Sep; 72(18):3457-88. Epub 2015 May 29.

  6. Identification and initial functional characterization of a human vascular cell-enriched long noncoding RNA., Bell RD, Long X, Lin M, Bergmann JH, Nanda V, Cowan SL, Zhou Q, Han Y, Spector DL, Zheng D, Miano JM, Arteriosclerosis, Tthrombosis, and Vascular Biology, 34(6):1249-59, 2014.

  7. Lost in transgenesis: A users guide for genetically manipulating the mouse in cardiac research. Davis J, Maillet M, Miano JM, Molkentin JD, Circ. Res. 111:761-777, 2012.

  8. 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.

  9. 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.

  10. 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

  11. 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:PubMed

Miano's Suggested Links

Research Gate https://www.researchgate.net/home

UCSC Genome Bioinformatics

Vista Tools

CRISPR/Cas Resources