Joseph M. Miano, Ph.D.

Joseph M. Miano, Ph.D.

Contact Information

Aab Cardiovascular Research Institute
601 Elmwood Avenue
Rochester, NY 14642

Office: (585) 276-7703
Fax: (585) 276-1530
Lab: (585) 276-7725
Administrative: (585) 276-7697

Lab Information

Transcriptional regulation of gene expression; pathobiology of SRF and myocardin; genome mining; genome editing with CRISPR/Cas9.

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Professional Bio

Dr. Joseph M. Miano received his Ph.D. in Experimental Pathology from New York Medical College in 1992. His post-doctoral training was done in Eric Olson's laboratory at the University of Texas M.D. Anderson Cancer Center where he cloned and characterized several smooth muscle-restricted promoters and initiated the study of retinoids in the vessel wall. Prior to his appointment at the U of R, Dr. Miano was an Assistant Professor in the Department of Physiology at the Medical College of Wisconsin where his genomics interests were developed and cultivated through collaborative work with Howard Jacob's lab. Dr. Miano served as an editorial board member for several journals and was Associate Editor of ATVB and a Consulting Editor for Circulation Research. He is a Fellow of the American Heart Association and a member of the Vascular Cell and Molecular Biology Study Section at NIH.

Research Bio

The human genome is replete with functional information, including millions of transcription factor binding sites (TFBS) that bind some 1400 transcription factors and several classes of non-coding RNA genes, particularly the rapidly growing class of long non-coding RNA (lncRNA). Thus, the long-held notion that the human genome is made up largely of "junk DNA" has been debunked and a new era has emerged to elucidate the functionality of the non-protein coding genome which comprises 98% of our blueprint of life.

Though the ENCODE Consortium and other big genome projects have been a magnificent kick-start for this new endeavor, much remains to be learned across the ~250 distinct cell types that make up the human body, especially under stress conditions that simulate disease processes. Accordingly, research in the Miano Lab is focused broadly on the vascular smooth muscle cell (VSMC) and how this cell type's differentiation program is controlled through both key TFBS and lncRNAs. Much of the work revolves around a DNA-binding transcription factor called serum response factor (SRF), its TFBS known as a CArG box, and an SRF cofactor called Myocardin (MYOCD), which his lab first showed to be a potent stimulus for the VSMC differentiation program. Current funded projects involve the study of a protein-coding gene (AKAP12A) that is a direct target of the SRF-Myocardin switch; the regulation of MYOCD and its role in vascular diseases; and the elucidation of the CArGome (all functional CArG boxes in the genome).

The latter project is also aimed to gain insight into CArG-SNPs that may be linked to human diseases. Since the vast majority of the >3.6 million CArG boxes punctuating the human genome fall in intergenic or intronic sequence space where "pervasive transcription" is known to occur, the lab initiated several screens to define known and novel lncRNAs in human VSMC. A major focus of the lab is obtaining functional insight into a novel lncRNA (SENCR) enriched in vascular cells as well as a number of known and novel lncRNAs that are regulated by SRF and/or MYOCD. The project pipeline involves a systematic series of experiments to define expression of lncRNAs in human tissues and cell lines; elucidating full length transcripts by RACE; defining spatial localization of lncRNAs by RNA-FISH; ascertaining potential regulatory sequences within lncRNAs (e.g., microRNA binding site, TFBS, etc); defining lncRNA promoters and the signaling molecules that converge upon regulatory sequences therein; defining altered transcriptomes by RNA-seq following loss-of-function with dicer substrate siRNAs directed to several regions of a lncRNA; and lncRNA interaction studies with other RNAs or proteins to begin understanding mechanistic aspects of lncRNAs. The Miano Lab utilizes state-of-the-art tools in genetics (e.g., HDR-mediated genome editing with CRISPR-Cas9), genomics, bioinformatics, and molecular biology to elucidate regulatory element and lncRNA biology in experimental and clinically relevant settings.

Awards & Honors (Local)

Vascular Biology Special Recognition Award 2014
Established Investigator Award American Heart Association 2003 - 2007
Who's Who in Medicine and Healthcare 2003
Manitowoc Heart-A-Rama Research for Life | American Heart Association (AHA) | Wisconsin Affiliate 1997
Post-Doctoral National Research Service, Smooth Muscle Cell Differentiation | National Institutes of Health | MD Anderson Cancer Center 1993
Helen S. Page Memorial Ph.D. 1992

Recent Journal Articles

Showing the 5 most recent journal articles. 115 available »

2016 Oct 1
Chettimada S, Joshi SR, Dhagia V, Aiezza A, Lincoln TM, Gupte R, Miano JM, Gupte SA. "Vascular smooth muscle cell contractile protein expression is increased through protein kinase G-dependent and -independent pathways by glucose-6-phosphate dehydrogenase inhibition and deficiency." American journal of physiology. Heart and circulatory physiology. 2016 Oct 1; 311(4):H904-H912. Epub 2016 Aug 12.
2016 Oct
Zhao J, Zhang W, Lin M, Wu W, Jiang P, Tou E, Xue M, Richards A, Jourd'heuil D, Asif A, Zheng D, Singer HA, Miano JM, Long X. "MYOSLID Is a Novel Serum Response Factor-Dependent Long Noncoding RNA That Amplifies the Vascular Smooth Muscle Differentiation Program." Arteriosclerosis, thrombosis, and vascular biology. 2016 Oct; 36(10):2088-99. Epub 2016 Jul 21.
2016 Jun
Miano JM, Zhu QM, Lowenstein CJ. "A CRISPR Path to Engineering New Genetic Mouse Models for Cardiovascular Research." Arteriosclerosis, thrombosis, and vascular biology. 2016 Jun; 36(6):1058-75. Epub 2016 Apr 21.
2016 May 24
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. "Smooth Muscle Enriched Long Noncoding RNA (SMILR) Regulates Cell Proliferation." Circulation. 2016 May 24; 133(21):2050-65. Epub 2016 Apr 06.
2016 May
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. "A Role for the Long Noncoding RNA SENCR in Commitment and Function of Endothelial Cells." Molecular therapy : the journal of the American Society of Gene Therapy. 2016 May; 24(5):978-90. Epub 2016 Feb 22.

Current Appointments

Associate Director - Aab Cardiovascular Research Institute
Professor - Department of Medicine, Aab Cardiovascular Research Institute (SMD) - Primary


PhD | Experimental Pathology | New York Medical College1992
MS | Experimental Pathology | New York Medical College1988
BS | Biology | SUNY Coll at Cortland1986

Post-Doctoral Training & Residency

Department of Biochemistry & Molecular Biology, University of Texas, MD Anderson Cancer Center, Houston Texas. (Eric Olson, Mentor) 1995