Using the prostaglandin signaling cascade to mitigate the effects of acute and delayed radiation exposure to hematopoiesis and blood cell function.
The objectives of this proposal are to investigate the ability of dmPGE2 to protect and mitigate the effects of radiation exposure on hematopoiesis and multi-organ dysfunction
Role of PGE2 and other eicosanoids in hematopoietic stem cell function.
This project will define the roles of EP4 signaling in the hematopoietic niche that regulate normal and stressed hematopoiesis is.
A megakaryocyte/PGE2/osteoblast triad in the normal and aged niche.
This project will define the regulatory interactions of PGE2, megakaryocytes, bone forming osteoblasts and mesenchymal stem cells in normal young and aged mice at homeostasis and after irradiation.
NCI Inhibition of PGE2 for mobilization of autologous peripheral blood stem cells.
The objectives of this proposal are to run a phase II clinical trial to assess the safety and efficacy of NSAIDs with G-CSF for autologous mobilization in patients with MM and NHL and molecularly characterize the NSAID assisted graft.
Mitigation of the Hematopoietic and Gastrointestinal Acute and Delayed Radiation Syndromes Using Combination Therapy with Pegylated Hematopoietic Growth Factors
Regulation of Hematopoietic Cell Production. This is a training grant.
Sex/gender differences in hematopoietic function and the stem cell niche.
P Singh, S Fukuda, LM Pelus. Survivin is required for mouse and human mesenchymal stem cell proliferation, survival and differentiation. Stem Cells, In Press 2017.
AM Patterson and LM. Pelus. G-CSF in stem cell mobilization: new insights, new questions. Annals of Blood, In Press 2017.
P Singh, J Hoggatt, M Kamocka, KS Mohammad, MR Saunders, H Li, JM Speth, N Carlesso, T Guise, LM Pelus. Enzymatic cleavage of neuropeptide Y regulates a vascular gateway for hematopoietic stem and progenitor cells. J Clin Investigation, In Press, 2017.
J Hoggatt, P Singh, TA. Tate, B-K Chou, S Datari, S Fukuda, L Liu, PV Kharchenko, A Schajnovitz, N Baryawno, F Mercier, J Boyer, D Morrow, DT Scadden, Louis M. Pelus. Rapid mobilization reveals a highly engraftable hematopoietic stem cell. Cell, In Press, 2017.
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 functions and regulates proliferation of hematopoietic stem cells through Evi-1. Leukemia 29:433-440, 2015. [PMID: 24903482].
A Balogh , Y Shimizu , SC Lee, R Gangwar, DD Norman, M Bavaria, CS Moon, P Shukla, R Rao, R Ray, AP Naren, S Banerje, DD Miller, L Balazs, LM Pelus, G Tigyi. The autotaxin-LPA2 GPCR axis is modulated by g-irradiation and facilitates DNA damage repair. Cell Signal Sep 27 9: 1751-1762, 2015. [PMID: 26027517].
HE Broxmeyer, LM Pelus. Inhibition of DPP4/CD26 and dmPGE2 treatment enhances engraftment of mouse bone marrow hematopoietic stem cells. Blood Cells Mol Dis, 2014 Mar3, 53:34-38 pii: S1079-9796(14)00008-4. doi: 10.1016/j.bcmd.2014.02.002. [PMID:24602918].
J Hoggatt, KS Mohammad, P Singh, AF Hoggatt, BR Chitteti, JM Speth, P Hu, BA Poteat, KN Stilger, F Ferraro, L Silberstein, FK Wong, SS Farag, M Czader, GL Milne, RM Breyer, CH Serezani, DT Scadden, TA Guise, EF Srour, LM Pelus. Differential stem- and progenitor-cell trafficking by prostaglandin E2. Nature, 2013, 21;495(7441):365-9, doi:1038/nature11929. Epub 2013 Mar 13 [PMCID: PMC3606692].
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, doi:10.1016/j.bcmd.2012.11.006. [PMID:23206586].
C Cutler, P Multani, D Robbins, HT Kim, T Le, J Hoggatt, LM Pelus, et al. Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. Blood, Blood. 2013 Oct 24;122(17):3074-81. doi: 10.1182/blood-2013-05-503177. Epub 2013 Aug 30. [PMID:23996087].
J Hoggatt, K Mohammed, P Singh and 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. doi: 10.1182/blood-2013-07-515288. Epub 2013 Sep18. [PMID:24047650].
JM Speth, J Hoggatt, P Singh, LM Pelus. Pharmacologic increase in HIF1 enhances hematopoietic stem and progenitor homing and engraftment. Blood, 2014, Jan 9;123(2):203-207. Doi:10.1182/blood-2013-07-516336. 2013 Oct 28. [Epub ahead of print] [PMID:24167196].
Faculty Research Team
Additional Research Team Members
Other research team members in the Pelus Lab include Liqiong Liu, PhD (Post-doctoral Fellow) and Andrea Patterson (Post-doctoral Fellow).