Key words: non-coding RNAs, gene regulation, functional genomics, computational biology, diabetes and metabolism
The overall goal of my research program is to define the role of non-coding RNAs in gene regulatory networks that contribute to the molecular pathology of complex diseases, with a primary focus on metabolic syndromes. Specifically, my lab investigates:
(1) the contribution of small RNA networks to gene expression dynamics;
(2) small RNA mediated regulation of lipid/glucose metabolic homeostasis;
(3) non-coding RNAs as both biomarkers of physiologic status and therapeutic targets;
(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 one post-doctoral trainee, four doctoral students in the Biological & Biomedical Sciences Program, one senior research specialist, and an experienced research technician.
Kristin Young (Primary mentor: Kari North)
Genetics of obesity
Tim Dinh (MD/PhD Program)
Jeanette Baran-Gale (BCB Curriculum)
Project: Modeling microRNA contributions to dynamic cellular processes
Bailey Peck (GMB Curriculum)
Project: Discovering microRNA networks that regulate intestinal renewal
Sara Selitsky (BCB Curriculum, Co-mentor: Stanley Lemon)
Project: Small RNAs in liver disease
C. Lisa Kurtz
Project: microRNAs in diabetes and dyslipidemia
Emily E. Fannin
Project: microRNAs in diabetes and dyslipidemia
Brendan Bulik-Sullivan (Research Assistant); Current position: Research assistant in the Daly Lab (Broad)
- Kasey Vickers, Ph.D. (Vanderbilt University, Department of Medicine)
- Samir Kelada, Ph.D. (UNC Chapel Hill, Department of Genetics)
- Stanley Lemon, M.D. (UNC Chapel Hill, Department of Microbiology)
- Mohanish Deshmukh, Ph.D. (UNC Chapel Hill, Department of Cell Biology and Physiology)
- Jeremy Purvis, Ph.D. (UNC Chapel Hill, Department of Genetics)
- P. Kay Lund, Ph.D. (UNC Chapel Hill, Department of Pediatrics)
- Kari North, Ph.D. (UNC Chapel Hill, Department of Epidemiology)
- Chris Newgard, Ph.D. (Duke University, Department of Pharmacology and Cancer Biology)
- Sudha Biddinger, Ph.D. (Harvard University, Department of Pediatrics)
- Mark Wilson, Ph.D. (MRC National Institute for Medical Research, London)
- Next-generation RNA (total and small) sequencing and analysis
- Computational biology
- Molecular RNA biology
- In vivo mouse models
- Genetic analysis of complex traits and diseases
- Bioinformatics and Computational Biology (BCB)
- Genetics and Molecular Biology (GMB)
- BCB 722: Foundations of population genomics
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:
- T.S. Furey and P. Sethupathy (2013). Genetics driving epigenetics. Science, 342:705-706.
- 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.