Joseph M. Miano, Ph.D.

Joseph M. Miano, Ph.D.

Contact Information

Aab Cardiovascular Research Institute
211 Bailey Road
West Henrietta, NY 14586

Office: (585) 276-9789
Fax: (585) 276-9830
Lab: (585) 276-9851
Administrative: (585) 276-9802

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 a bewildering array of "information packets" including millions of transcription factor binding sites (TFBS) and a menagerie of non-coding RNAs, 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 define the functionality of the non-protein coding genome which comprises 98% of our blueprint for 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 clinical contexts.

Awards & Honors (Local)

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. 101 available »

2014 Jun
Bell RD, Long X, Lin M, Bergmann JH, Nanda V, Cowan SL, Zhou Q, Han Y, Spector DL, Zheng D, Miano JM. "Identification and initial functional characterization of a human vascular cell-enriched long noncoding RNA." Arteriosclerosis, thrombosis, and vascular biology.. 2014 Jun; 34(6):1249-59. Epub 2014 Feb 27.
2014 Apr 15
Fisher EA, Miano JM. "Don't judge books by their covers: vascular smooth muscle cells in arterial pathologies." Circulation.. 2014 Apr 15; 129(15):1545-7.
2014
Shi F, Long X, Hendershot A, Miano JM, Sottile J. "Fibronectin matrix polymerization regulates smooth muscle cell phenotype through a Rac1 dependent mechanism." PloS one. 2014 9(4):e94988. Epub 2014 Apr 21.
2013 Oct
Long X, Miano JM. "Myocardin: new therapeutic agent in vascular disease?" Arteriosclerosis, thrombosis, and vascular biology.. 2013 Oct; 33(10):2284-5.
2013 Sep
Imamura M, Sugino Y, Long X, Slivano OJ, Nishikawa N, Yoshimura N, Miano JM. "Myocardin and microRNA-1 modulate bladder activity through connexin 43 expression during post-natal development." Journal of cellular physiology.. 2013 Sep; 228(9):1819-26.

Current Appointments

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

Education

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