Sharma Lab

Girdhar Sharma, PhD
Assistant Professor of Radiation Oncology

Girdhar Sharma, PhD is an R01 funded investigator who studies the molecular regulation of stem cell radiation response. Goal of his research work is to delineate the molecular signaling and epigenetic regulators of normal stem cell hypersensitivity to ionizing radiation (IR) and validate them as molecular targets for radioprotection. His laboratory uses multifaceted approaches to unravel the novel associations between signaling molecules, epigenetic modifiers and cellular differentiation states; in the regulation of stem cell specific DNA damage response (DDR) and apoptotic responses (AR). Insights into the mechanistic interplay of signal transduction networks and chromatin states unique to stem cells, as against their non-stem progeny is crucial for developing therapeutic prevention/ intervention strategies of radioprotection; to effectively minimize IR induced stem cell dropout and the associated debilitating side effects of cancer radiotherapy. Investigation of normal tissue stem cells compared to the differentiated non-stem cells in vivo has led to identification of key molecular targets to modulate radiosensitivity. His laboratory is delineating the dual role of PP2A phosphatase in stem cell DDR and AR, and characterizing specific and cumulative roles of histone H3K56ac, H3K9ac/me and pH2AX-Y142 in stem cell IR responses and validating the radioprotection efficacy of these pluralistic regulators of stem cell radiosensitivity (Jacobs KM et al. Mol Biol Cell. 27(8)1332-45 (2016). PMID: 26941327 PMCID: PMC4831886; Meyer B et al. Stem Cell Reports. 7(6)1013-22 (2016). PMID: 27974220 PMCID: PMC5161741). In collaboration with the molecular modeling and medicinal chemistry experts, Dr. Sharma is developing drugs to specifically inhibit key molecular regulators for radioprotection of normal stem cells. These stem cell specific radioprotectors would increase the efficacy of radiotherapy by minimizing normal stem cell dropout without protecting cancer and will directly help improving the quality of life of cancer survivors.

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Faculty Bio

For more information about research opportunities in this laboratory, please contact Dr. Girdhar Sharma (sharma@wustl.edu).

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