- Mechanisms regulating hematopoiesis
- Hematopoietic stem cell (HSC) transplantation
- Bone marrow failure disorders
- Graft versus host disease
- HSC expansion methods
- Regenerative medicine
Hematopoietic stem cell (HSC) transplantation (HST) is a curative treatment for many hematopoietic malignancies that involves the IV infusion of stem cells to reconstitute recipient immune function. However, many significant HST related complications limit the current utility of the procedure; including severe infections and bleeding, high incidence of graft vs. host disease, graft failure, and a lengthy recovery period which can drive the cost of the procedure to nearly $500,000. Thus, while HST is curative in many settings, it is also both an expensive procedure and a risky one.
The Desai lab is broadly interested in identifying mechanisms driving the regenerative capacity of HSCs during HST, in order to develop novel therapeutics capable of reducing morbidity, mortality, and expense of human HST, making the procedure safer, faster, and more affordable.
Current Lab Directions
- Small molecule development of 15-PGDH inhibitors to promote hematopoietic recovery following HST.
- Additional therapeutic application of 15-PGDH inhibitors including in models of graft versus host disease, bone marrow failure disorders, and other heme malignancies.
- Identification of novel cell types regulating hematopoietic stem cell regulation at steady state and in the context of tissue regeneration.
- Mechanisms of disease pathogenesis for myelodysplastic syndromes and myelofibrosis.
Patel, R. Zhang, L. Desai, A. Hoenerhoff, MJ. Kennedy, LH. Radivoyevitch, T. Ban, Y. Chen, XS. Gerson, SL. Welford, SM. Mlh1 deficiency increases the risk of hematopoietic malignancy after simulated space radiation exposure. Leukemia. October 2018.
Desai A, Zhang Y, Dawson DM, Larusch GA, Kasturi L, Wald, D, Gerson SL, Markowitz SD. A second-generation 15-PGDH inhibitor promotes bone marrow transplant recovery independent of age, transplant dose, and G-CSF support. Haematologica. June 2018.
Patel, R. Qing, Y. Kennedy, L. Yan, Y. Pink, J. Aguila, B. Desai, A. Gerson, SL. Welford, SM. MMR Deficiency Does Not Sensitize or Compromise the Function of Hematopoietic Stem Cells to Low and High LET Radiation. Stem Cells Translational Medicine. April 2018.
Folashade O, Moreton S, Ojo E, Mackowski N, Desai A, Markowitz S, Wald D. Enhancing trafficking of adoptively transferred natural killer cells via Prostaglandin E2 signaling. Biology of Blood and Marrow Transplantation. March 2016. Pp. S477-S478.
Desai A, Zhang Y, Yang SY, Bae KB, Antczak MI, Fink SP, Tiwari S, Willis JE, Williams NS, Dawson DM, Wald D, Chen WD, Wang Z, Kasturi L, Larusch GA, He L, Cominelli F, Di Martino L, Djuric Z, Milne GL, Chance M, Sanabria J, Dealwis C, Mikkola D, Naidoo J, Wei S, Tai HH, Gerson SL, Ready JM, Posner B, Willson JK, Markowitz SD. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. Science. June 2015.
Desai A, Gerson SL. Exo1 Independent DNA Mismatch Repair Involves Multiple Compensatory Nucleases. DNA Repair. September 2014. pp. 55-64.
Desai A, Webb B, Gerson, SL. CD133+ cells contribute to radioresistance via altered regulation of DNA repair genes in human lung cancer cells. Radiotherapy and Oncology. March 2014. pp. 538-45.
Desai A, Qing Y, Gerson SL. Exonuclease 1 is a critical mediator of survival during DNA double strand break repair in non-quiescent hematopoietic stem and progenitor cells. Stem Cells. February 2014. pp.582-93.
Zhou G, Hamik A, Nayak L, Tian H, Shi H, Lu Y, Sharma N, Liao X, Hale A, Boerboom L, Feaver RE, Gao H, Desai A, Schmaier A, Gerson SL, Wang Y, Atkins GB, Blackman BR, Simon DI, Jain MK. Endothelial Kruppel-like factor 4 protects against atherothrombosis in mice. J Clin Invest. December 2012. pp. 4727-31.
Schormann N, Velu SE, Murugesan S, Senkovich O, Walker K, Chenna BC, Shinkre B, Desai A, Chattopadhyay D. Synthesis and Characterization of Potent Inhibitors of Trypanosoma cruzi Dihydrofolate Reductase. Bioorg Med Chem. June 2010. pp. 4056-66.
Maeda A, Maeda T, Golczak M, Chou S, Desai A, Hoppel CL, Matsuyama S, Palczewski K. Involvement of all-trans retinal in acute light-induced retinopathy of mice. J. Biol Chem. May 2009. pp. 1-17.
Desai, A. Yan, Y. Gerson, SL. Cancer Stem Cell Targeted Therapies: Towards Clinical Success. Stem Cells Translational Medicine. October 2018.
Desai, A. Yan, Y, Gerson, SL. Advances in therapeutic targeting of the DNA damage response in cancer. DNA Repair. April 2018.
Lin, Y. Desai, A. Gerson, SL. (2010). Lentiviruses: Vectors for Cancer Gene Therapy. In Jack A. Roth (Ed.), Gene Based Therapies for Cancer (155-179). Springer. Book Chapter.