Joseph Miano, Ph.D.
Aab Cardiovascular Research Institute
University of Rochester School of Medicine and Dentistry
One focus of the lab is interrogating the human and mouse genomes for functional non-coding sequences. For example, we have used computational biology and next generation sequencing to identify thousands of conserved CArG boxes (CArGome), to which the SRF transcription factor binds. We have also pinpointed scores of CArG-SNPs that disrupt SRF binding and thus target gene expression. The latter have direct translational significance towards understanding complex human disease traits. The CArGome work has led us to the expansive class of long noncoding RNA genes and we recently reported one of the first human vascular cell-restricted lncRNAs (called SENCR). We continue to apply RNA-seq to the study of human vascular cells treated under a variety of experimental conditions for further identification of lncRNA genes. To test the functionality of noncoding sequences such as CArG boxes and lncRNA genes, we use the revolutionary CRISPR-Cas9 genome editing system. We recently reported the first ever unadulterated regulatory element mutation in mice wherein a CArG box was subtly changed to inhibit SRF binding; the result was a near complete erasure of target gene expression. This report paves the way for a new generation of studies that will use CRISPR-Cas9 to assess regulatory element function in a living animal. The lab has many CRISPR-Cas9 mouse projects underway, including the modeling of human SNPs linked to disease.
Find more information on the web: http://www.urmc.rochester.edu/cvri/research/miano-lab/
Members of the laboratory:
Joseph Miano, Principal Investigator
Orazio Slivano, Technical Associate
Christine Christie, Technician
Yu Han, Staff Scientist
Bing Guo, Post-doctoral Fellow
- Miano, JM. Myocardin in biology and disease. J.Biomed.Res. 29(1):3-19, 2015.
- Han Y, Slivano OJ, Christie C, Cheng AW, Miano JM. CRISPR-Cas9 genome editing of a single regulatory element nearly abolishes target gene expression in mice. Arterioscler.Thromb.Vasc.Biol. 35:312-315, 2015. Editor's Pick, Cover image, and Editorialized in K Musunuru, ATVB.
- 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 non-coding RNA. Arterioscler.Thromb.Vasc.Biol. 34:1249-59, 2014. (Editor's pick and Editorialized by Thum, ATVB).
Charles Lowenstein, University of Rochester Medical Center
William Sessa, Yale University
Deepak Srivastava, Gladstone Laboratories, UCSF
Edward Fisher, NYU School of Medicine
Xiaochun Long, University of Rochester Medical Center
Seungil Ro, University of Nevada
Nanjing Medical University, Defining Noncoding Sequence Function in Vascular Biology, April 23, 2015.
"Whatever it takes"