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Pratibha Singh, Ph.D.

Assistant Research Professor

Summary of the focus of the research

My research focuses on understanding mechanisms that regulate normal and stressed hematopoietic stem and progenitor proliferation, differentiation and survival, and the role played by bone marrow niche support cells in hematopoietic stem cell function.

 

Description and summary of research focus of the laboratory

Current clinical hematopoietic transplant (HCT) relies on moving HSPC from bone marrow (BM) to the circulation, a process called peripheral blood stem cell mobilization (PBSCM), with G-CSF (Neupogen) being the primary drug used clinically for PBSCM. However, little is known about the mechanisms governing HSPC egress. Understanding this process has major relevance for clinical HCT. Poor homing and inadequate expansion, survival and differentiation of transplanted HSPC can limit transplant efficacy. Understansing hematopoietic stem cell regulation will allow us to develop improved stratiegies for hematopoietic stem cell based therapies, and facilitate recovery of hematopoieisis following stress and injury such as chemo/radio therapy or acute radiation exposure. My research interests include identifying mechanisms of action of Neuropeptide Y on hematopoietic cells and on the function of stromal niche support cells and in regulation of hematopoietic stem and progenitor cells trafficking. I am currently exploring the role of sinusoidal endothelial cells in hematopoietic stem cell maintenance and trafficking and have identified an unappreciated role for DPP IV- Neuropeptide Y axis in regulation of endothelial cell barrier permeability and hematopoietic stem cell trafficking. I am also investigating the role of Survivin in regulating mesenchymal stem cell functions and I have identified a previously unknown role for Survivin in the mesenchymal stem cell survival/proliferation and maintenance of hematopoietic stem cell niche. My emerging interest is to investigate the role of stromal cell populations in regulation of hematopoiesis following stress, particularly in niche regeneration after myeloablative injury such as radiation exposure.

  • S Fukuda, J Hoggatt, P Singh, M Abe, JM Speth, P Hu, EM Conway, G Nucifora, S Yamaguchi, LM Pelus. Survivin modulates genes with divergent molecular functions and regulates proliferation of hematopoietic stem cells through Evi-1. Leukemia, 2014 Jun 6, doi:10.1038/leu.2014.183 [PMID 24903482]
  • LM Pelus, P Singh, Delta-1 provides pleasant stem cell environs. Blood, 2014 Jan 30;123(5):605-6. [PMID: 24482496]
  • JM. Speth, J Hoggatt, P Singh, LM Pelus,Pharmacologic increase in HIF1α enhances hematopoietic stem and progenitor homing and engraftment. Blood, 2014 Jan 9;123 (2):203-7.[PMC3888286]
  • J Hoggatt, KS Mohammad, P Singh, LM. Pelus, Prostaglandin E2 enhances long-term repopulation but does not permanently alter inherent stem cell competitiveness. Blood, 2013 Oct 24;122 (17):2997-3000. [PMC3811174]
  • J Hoggatt , K Muhammad, P Singh, A Hoggatt, BR  Chitteti, J Speth, P Hu, B Poteat, S  Farag, M Czader, R Breyer, D Scadden , T Guise, E Srour and LM  Pelus. Differential stem-and progenitor-cell trafficking by prostaglandin E2. Nature, 2013 Mar 21;495 (7441):365-9. [PMC3606692]  (contributed equally)
  • J Hoggatt, P Singh, KN Stilger, PA Plett, CH Sampson, HL Chua, CM Orschell, LM Pelus. Recovery from hematopoietic injury by modulating prostaglandin E (2) signaling post-irradiation. Blood Cells Mol Dis. 2013 Mar;50 (3):147-53 [PMC:3566353]
  • P Singh,P Hu, J Hoggatt, A Moh and LM Pelus. Expansion of bone marrow neutrophils following G-CSF administration in mice results in osteolineage cell apoptosis and mobilization of hematopoietic stem and progenitor cells. Leukemia. 2012 Nov;26 (11):2375-83. [PMC3410045] 
  • P Singh, J Hoggatt, P Hu, JM Speth, S Fukuda, RM Breyer and LM Pelus, Blockade of prostaglandin E2 signaling through EP1 and EP3 receptors attenuates Flt3L-dependent dendritic cell development from hematopoietic progenitor cells. Blood, 2012; 119:1671-1682.[PMC3286345]

  • LM Pelus, J Hoggatt, P Singh, Pulse exposure of hematopoietic grafts to prostaglandin E2 in vitro facilitates engraftment and recovery. Cell Prolif., 2011; 1:22-9.[PMID:21481039]

  • S Fukuda, P Singh, A Moh, M Abe, EM Conway, HS Boswell, S Yamaguchi, X-Y Fu and LM Pelus, Survivin Mediates Aberrant Hematopoietic Progenitor Cell Proliferation and Acute Leukemia in Mice Induced by Internal-Tandem-Duplication of Flt3. Blood. 2009; 114:394-403.[PMC 2714213]
  • J Hoggatt, P Singh, J Sampath and LM Pelus, Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation. Blood, 2009; 113:5444-55.[PMC2689046]
  • P Singh, Y Yao, Al Weliver, HE Broxmeyer, S-C Hong, C-H Chang., Vaccinia virus infection modulates the hematopoietic cell compartments in the bone marrow.Stem Cells.2008; 26:1009-16.Epub 2008 Feb 7. [PMC2814369]

  • Y Yao, P Li, P Singh, AT Thiele, DS Wilkes, GJ Renukaradhya, RR. Brutkiewicz, JB Travers, GD Luker, S-Cl Hong, JS Blum and C-H Chang, Vaccinia virus infection induces dendritic cell maturation but inhibits antigen presentation by MHC class ll. Cell Immunol. 2007 Apr; 246(2):92-102.[PMC2100387]
  • M.Sc, 1998, Dr. Ram Manohar Lohia Avadh University, U.P., India                        
  • Ph.D., 2005, Sanjay Gandhi Postgraduate Institute of Medical Sciences, U.P., India
  • Post Doctoral, 2010, Indiana University School of Medicine, Indianapolis, Indiana
  • Research Associate, 2015, Indiana University School of Medicine, Indianapolis, Indiana

Department of Microbiology and Immunology | IU School of Medicine | 635 Barnhill Drive, MS 420 | Indianapolis, IN 46202 | (317) 274-0506