Assistant Professor

Research Interests

Key words: non-coding RNAs, gene regulation, functional genomics, computational biology, diabetes and metabolism

Research Description

The overall goal of my research program is to functionally characterize non-coding regulatory networks that contribute to the molecular pathology of a variety of complex diseases, including diabetes and immune-mediated conditions.  Specifically, my lab investigates:

(1)  the cellular mechanisms that control non-coding RNA expression;

(2)  small RNA mediated regulation of gene expression and metabolic homeostasis;

(3)  non-coding RNAs as both biomarkers of physiologic status and therapeutic targets for metabolic disorders;

(4)  regulatory variants within the microRNA (miRNA) regulome that predispose to disease;

(5)  and novel forms of intercellular communication via regulated transfer of small RNAs.

The research paradigm in my lab is highly interdisciplinary, with lab members regularly engaged in molecular biology, biochemistry, bioinformatics, genomic sequence analysis, and computational biology.  The lab is presently composed of two senior research specialists, an experienced research technician, and three doctoral students in the Biological & Biomedical Sciences Program.

Lab Members

Trainees

• Jeanette Baran-Gale (PhD Student, BCB Curriculum)
• Bailey Peck (PhD Student, GMB Curriculum)
• Sara Selitsky (PhD Student, BCB Curriculum, Co-mentor: Dr. Stanley Lemon)
• Kristin Young (Post-doctoral Fellow, Primary mentor: Dr. Kari North)

Research Specialists

• Emily E. Fannin (Research Technician)
• C. Lisa Kurtz (Research Specialist)
• Vandana Turaga (Research Specialist)

Lab Alumni

• Brendan Bulik-Sullivan (Research Assistant, Presently at the Broad Institute)

Recent Collaborators

• Dr. Kasey Vickers (Vanderbilt University, Department of Medicine)
• Dr. Samir Kelada (UNC Chapel Hill, Department of Genetics)
• Dr. Stanley Lemon (UNC Chapel Hill, Department of Microbiology)
• Dr. Mark Wilson (MRC National Institute for Medical Research, London)
• Dr. Alain Laederach (UNC Chapel Hill, Department of Biology)
• Dr. Kari North (UNC Chapel Hill, Department of Epidemiology)
• Dr. Peter Schwarz (University of Dresden, Department of Medicine)
• Dr. Chris Newgard (Duke University, Department of Medicine)
• Dr. Sudha Biddinger (Harvard University, Department of Pediatrics)
• Dr. Francis Collins (National Institutes of Health, NHGRI)

Core Techniques

• Next-generation RNA (total and small) sequencing and analysis
• Integrative genomic data analysis
• Computational biology
• Molecular RNA biology
• Genetic analysis of complex traits and diseases

Graduate Curriculums

• Bioinformatics and Computational Biology (BCB)
• Genetics and Molecular Biology (GMB)

Courses

• BCB 722: Foundations of population genomics

Publications

Representative original publications:

• B. Bulik-Sullivan, S. Selitsky and P. Sethupathy (2013). Prioritization of genetic variants in the microRNA regulome as functional candidates in genome wide association studies. Human Mutation, doi:10.1002/humu.22337.
• K.C. Vickers, B. Shoucri, M.G. Levin, H. Wu, D.S. Pearson, D. Osei-Hwedieh, F.S. Collins, A.T. Remaley* and P. Sethupathy* (2013). MicroRNA-27b is a regulatory hub in lipid metabolism and is altered in dyslipidemia. Hepatology, doi: 10.1002/hep.25846.
• S. Paredes, M.F. Melgar and P. Sethupathy (2012). Promoter proximal CTCF binding is associated with an increase in the transcriptional pausing index. Bioinformatics, doi:10.1093/bioinformatics/bts596.
• C.L. Avery, P. Sethupathy, S. Buyske, Q.C. He, D.Y. Lin, D.E. Arking, C. Carlson, C.L. Carty, D. Duggan, M.D. Fesinmeyer, L.A. Hindorff, J.M. Jeff, C. Kooperberg, L. Klein, K.K. Patton, U. Peters, R. Shohet, N. Sotoodehnia, A.M. Young, C.A. Haiman, K.L. Mohlke, E.A. Whitsel and K. North (2012). Fine-mapping and initial characterization of QT interval loci in African American populations. PLoS Genetics, 8:e1002870.
• M.F. Melgar, F.S. Collins* and P. Sethupathy* (2011). Discovery of active enhancers through bidirectional expression of short transcripts. Genome Biology, 12:R113. Highly Accessed
• M.L. Stitzel*, P. Sethupathy*, D.S. Pearson, P.S. Chines, L. Song, M.R. Erdos, R. Welch, L.J. Scott, NIH Intramural Sequencing Center Team, M. Boehnke, T. Furey, G.E. Crawford and F.S. Collins (2010). Global epigenomic profiling of human pancreatic islets provides insights into type 2 diabetes susceptibility loci. Cell Metabolism, 12:443-455.
• L.A. Hindorff*, P. Sethupathy*, H.A. Junkins, E.A. Ramos, J.P. Mehta, F.S. Collins and T.A. Manolio (2009). Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. PNAS, 106:9362-9367.
• P. Sethupathy, H. Giang, J.B. Plotkin and S. Hannenhalli (2008). Genome-wide analysis of natural selection on human cis-elements. PLoS One, 10:e3137.
• P. Sethupathy*, C. Borel*, M. Gagnebin, G.R. Grant, S. Deutsch, T.S. Elton, A.G. Hatzigeorgiou and S.E. Antonarakis (2007). Human miR-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3’UTR – a mechanism for functional SNPs related to phenotypes. American Journal of Human Genetics, 81:405-413. Selected by Faculty of 1000 Biology
• Y. Kawahara, B. Zinshteyn, P. Sethupathy, H. Iizasa, A.G. Hatzigeorgiou and K. Nishikura (2007). Redirection of silencing targets by adenosine-to-inosine editing of microRNAs. Science, 315:1137-1140.

Representative perspective/review articles:

• P. Sethupathy (2013). The needles in the genetic haystack of lipid disorders: single nucleotide polymorphisms in the microRNA regulome. Journal of Lipid Research, 54:1168-1173.
• K.C. Vickers*, P. Sethupathy*, J.B. Gale and A.T. Remaley (2013). The complexity of microRNA function and the role of isomiRs in lipid homeostasis. Journal of Lipid Research, 54:1182-1191.
• P. Sethupathy (2013). Illuminating microRNA transcription from the epigenome. Current Genomics, 14:68-77.
• P. Sethupathy and S. Hannenhalli (2008). A tutorial of the Poisson Random Field model in population genetics. Advances in Bioinformatics, 2008:257864.
• P. Sethupathy, M. Megraw and A.G. Hatzigeorgiou (2006). A guide through current computational approaches for the identification of mammalian microRNA targets. Nature Methods, 3:881-886.