Sridhar Rao_Photo

Sridhar Rao, MD, PhD

Associate Investigator
Blood Research Institute
BloodCenter of Wisconsin


Education and training
Postdoctoral Research Training
Dana Farber Cancer Institute and Children’s Hospital, Boston, MA

Clinical Training

Dana Farber Cancer Institute and Children’s Hospital, Boston, MA

Contact information
Phone: (414) 937-3841
Fax: (414) 937-6284
E-mail:
sridhar.rao@bcw.edu

Stem Cell Biology / Hematopoiesis
Stem cells are defined by two unique properties: self-renewal, or the ability to undergo symmetric cell division to maintain a stable pool, and "potency", or the ability to differentiate down multiple lineages. In the case of embryonic stem (ES) cells, their unique ability to differentiate into all three germ layers that form the embryo is termed pluripotency. Adult stem cells, such as the hematopoietic stem cell (HSC), are more restricted in their differentiation potential, but can fully recreate a tissue in vivo. Recently, the stem cell model has been extended into cancer, with cancer stem cells identified in certain malignancies such as acute myeloid leukemia (AML). While many of the factors required for stem cells are well described, none have been shown to play a critical role in all types of stem cells. Factors critical for all three stem cell types would likely operate by controlling a specific "stemness program" used by all stem cells for self-renewal and/or multipotency. Identification of such a program could provide new avenues to identify stem cells in vivo, enhance the reprogramming/generation of stem cells for use in regenerative medicine, and provide novel targets for the development of anti-cancer therapeutics.
 
The overall goal of my laboratory is to understand how transcription factors regulate the unique properties of stem cells, whether they are embryonic stem cells, adult stem cells, or cancer stem cells. Our current research aims to develop models in which the pathways regulated by transcription factors can be determined and compared in different types of stem cells, allowing us to develop a signature of “stemness.” Our lab uses mouse models of normal hematopoiesis and leukemia, embryonic stem cells, and multiple genome-wide approaches to elucidate the role of transcription factors. Our studies will eventually lead to new pathways that could be exploited in regenerative medicine strategies and targeted therapies for cancer.

Grants
NHLBI Career Development Award (K08) 2007-2012


Cary Stelloh

Research Technologist

Jonathan Peterson
Assistant Research Technologist

Sam Milanovich
Clinical Fellow

Michael Reimer
Graduate Student

Steven Blinka
Graduate Student

Kirthi Pulakanti
Computational Biologist

Selected Publications
  • Pulakanti, K., Pienello, L., Stelloh, C., Blinka, S., Allred, J., Milanovich, S., Peterson, J., Wang, A., Yuan, G.C*., and Rao, S.* (2013). Enhancer Transcribed RNAs are produced from hypomethylated genomic regions in a Tet-dependent manner.  Epigenetics. 8, 1303-1320: PMID: 24135681, PMCID in process. *co-senior authors. (http://dx.doi.org/10.4161/epi.26597)
  • Rao, S., Shao, Z., Roumiantsev, S., McDonald, L., Yuan, G., Orkin, S.H. (2010) Differential Roles of Sall4 Isoforms in Embryonic Stem Cell Pluripotency. MCB 30, 5364-80.
  • Orkin, S. H. Wang, J., Kim, J., Chu, J., Rao, S., Theunissen, T.W., Shen, X., and Levasseur, D.N. in Cold Spring Harbor Symposia on Quantitative Biology Vol. LXXIII (Cold Spring Harbor Laboratory Press, Cold Spring Harbor Laboratory 2008).
  • Wang, J., Trowbridge, J. J., Rao, S. & Orkin, S. H. Vol. StemBook.1.4.1 (eds B. E. Bernstein & I. Lemischka) (stembook.org, 2008).
  • Wang, J., Rao, S., Chu, J., Shen, X., Levasseur, D., Theunissen, T., Orkin, S.H.(2006) A protein interaction network for pluripotency of embryonic stem cells. Nature 44, 364-368.
  • Hu, C.J., Rao, S., Ramirez-Bergeron, D.L., Gerondakis, S., and Simon, M.C. (2001) PU.1/Spi-B regulation of c-rel¬ is essential for mature B cell survival. Immunity 15, 545-555
  • Garrett-Sinha, L.A, Dahl, R., Rao, S., and Simon, M.C. (2001) PU.1 exhibits partial functional redundancy with Spi-B, but not with Ets-1 or Elf-1. Blood 97, 2908-2912.
  • Rao, S., Garrett-Sinha, L., Yoon, J., and Simon, M. C. (1999). The Ets factors PU.1 and Spi-B regulate the transcription in vivo of P2Y10, a lymphoid restricted heptahelical receptor. J Biol Chem 274, 34245-52.
  • Rao, S., Matsumura, A., Yoon, J., and Simon, M. C. (1999). SPI-B activates transcription via a unique proline, serine, and threonine domain and exhibits DNA binding affinity differences from PU.1. J Biol Chem 274, 11115-24.

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