Sridhar Rao, MD, PhD

Stem Cell Biology / Hematopoiesis

The primary focus of our lab is to understand how changes in gene expression influence differentiation of stem cells. Alterations in this process are a key step in the development of leukemia. In particular, our laboratory focuses on how non-coding DNA elements act as “molecular switches” to causes changes in gene expression. We use different models to understand how non-coding DNA elements regulate which genes are on or off in a particular cell type, but one of our primary models is Acute Myeloid Leukemia (AML). We focus on AML because it has a poor long-term survival even with high dose chemotherapy, illustrating the need for more effective, less toxic therapies. In AML, approximately 15% of patients have mutations within genes encoding the cohesin complex, which plays a critical role in allowing non-coding DNA elements to regulate gene expression. In addition to AML, we also use mouse derived stem cells to ask fundamental questions about how non-coding DNA elements regulate gene expression. Most of our studies rely upon next-generation sequencing-based genome wide approaches, in addition to genomic editing to understand how non-coding DNA elements regulate stem cell differentiation.

• NCI: Cohesin Mutations in Acute Myelogenous Leukemia (PI) (09/19/2017 - 07/31/2022)
• NIDDK: GATA4 in Development of a Normal Squamocolumnar Junction and Barrett's Esophagus (Co-I) (07/01/2017 - 06/30/2019)

Kirthi Pulakanti
Computational Biologist

Alison Meyer
Research Scientist

Cary Stelloh
Research Technologist

Lauren Pommert
Clinical Fellow 

Katelyn Heimbruch
Graduate Student

Puja Agarwal
Graduate Student

• Rao S (2012). Embryonic Stem Cells: a perfect tool for studying mammalian transcriptional enhancers. J Stem Cell Res Ther, S10-007, PMCID3844140
• Blinka S, MH Reimer, K Pulakanti, L Pinello, GC Yuan, and S Rao (2017). Identification of Transcribed Enhancers by Genome-Wide Chromatin Immunoprecipitation Sequencing. Methods in Molecular Biology, Enhancer RNAs. Series Editor: John Walker; Book Editor: Ulf Andersson Orom. 1468:91-109 PMID27662872
• Fisher JB, M McNulty, MJ Burke, JD Crispino, and S Rao (2017). Cohesin Mutations in Myeloid Malignancies. Trends in Cancer, 3:282-293 PMCID in process.
• Blinka S and S Rao (2017). Nanog Expression in Embryonic Stem Cells-an Ideal Model System to Dissect Enhancer Function. BioEssays. Manuscript accepted
• Pulakanti K, L Pienello, C Stelloh, S Blinka, J Allred, S Milanovich, S Kiblawi, J Peterson, A Wang, GC Yuan*, and S Rao* (2013). Enhancer transcribed RNAs arise from hypomethylated, Tet-occupied genomic regions. Epigenetics 8:1303–1320. PMCID:3933491 *co-senior authors
• Boehler KR, S Bhattacharya, EM Kropp, S Chuppa, DR Riordon, D Bausch-Fluck, PW Burridge, JC Wu, RP Wersto, GC Chan, S Rao, B Wollscheid, and RL Gundry (2014). A human pluripotent stem cell surface N-glycoproteome resource reveals new markers, extracellular epitopes, and drug targets. Stem Cell Reports\ 3:185-203. PMCID:4110789
• Milanovich S, J Peterson, J Allred, C Stelloh, K Rajasekaran, J Fisher, SA Duncan, S Malarkannan, and S Rao (2015). Sall4 overexpression blocks murine hematopoiesis in a dose-dependent manner. Exp Hematology 43:53-64. PMCID:4268405
• Sohni A, M Bartoccetti, R Khoueiry, L Spans, J Vande Velde, L De Troyer, K Pulakanti, F Claessens, S Rao, and KP Koh (2015). Dynamic switching of active promoter and enhancer domains regulates Tet1 and Tet2 expression during cell state transitions between pluripotency and differentiation. Mol Cell Bio 35:1026-1042. PMCID:4333094
• Zhang N, H Zhi, BR Curtis, S Rao, C Jobaliya, M Poncz, DL French, and PJ Newman (2016). CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes. Blood, 127:675-80. PMCID:4751021
• Stelloh C, MH Reimer, K Pulakanti, S Blinka, J Peterson, L Pinello, S Jia, S Roumiantsev, MJ Hessner, S Milanovich, GC Yuan, and S Rao (2016). The cohesin-associated protein Wapal is required for proper polycomb-mediated gene silencing. Epigenetics and Chromatin 9:14. PMCID:4832553
• Blinka S, MH Reimer, K Pulakanti, and S Rao (2016). Super-Enhancers at the Nanog Locus Differentially Regulate Neighboring Pluripotency-Associated Genes. Cell Reports 17:19-28. PMCID:5111363
• Swartz KL, SN Woods, T Murthy, O Ramirez, G Qin, MM Pillai, S Rao, and AC Minella (2017) E2F-2 promotes nuclear condensation and enucleation of terminally differentiated erythroblasts. Mol Cell Biol 37:e00274-16. PMCID:5192079
• Fisher J, J Peterson, M Reimer, C Stelloh, K Pulakanti, ZJ Gerbec, AM Abel, J Strouse-Miksanek, C Strouse, M McNulty, S Malarkannan, JD Crispino, S Milanovich, and S Rao (2017). The cohesin subunit Rad21 is a negative regulator of hematopoietic self-renewal through epigenetic repression of HoxA7 and HoxA9. Leukemia 31:712-719. PMID:27554164
• Thompson CA, K Wojta, K Pulakanti, S Rao, P Dawson, and MA Battle M.A (2017). GATA4 is sufficient to establish jejunal versus ileal identity in the small intestine. Cell Mol Gastroenterology Hepatology. 3:422-446 PMCID5404030
• Fisher JB, K Pulakanti, S Rao, and SA Duncan (2017). GATA6 is essential for endoderm formation from human pluripotent cells. Biology Open. Accepted.

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