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Sharma, Sudha
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My lab is interested in understanding how mammalian cells maintain genomic stability under normal growth conditions and following DNA damage, and how loss of genetic integrity contributes to cancer, premature aging and other diseases. We utilize a combination of biochemical, molecular and cell biological tools to examine functions of RecQ helicases, a group of highly conserved DNA unwinding enzymes described as caretakers of the genome and implicated in rare genetic diseases. For the past few years, my lab has been investigating investigating RECQ1 (also known as RECQL or RECQL1), the most abundant human RecQ homolog, with a goal to determine common and specialized functions of human RecQ helicases in mechanisms of genome maintenance. The overall focus is on elucidating how impaired function of a specific RecQ protein relates to disease outcomes, including cancer predisposition and premature aging. Following my earlier discovery that the loss of RECQ1 is sufficient to cause genomic instability in mammalian cells, recent work in my lab is investigating in detail the specific roles of RECQ1 in genome maintenance mechanisms of DNA repair and transcriptional regulation, and exploring its broader significance in cellular homeostasis. RECQ1 is frequently upregulated in various cancers and is especially important for cancer cell proliferation. Additionally, germline mutations in RECQ1 significantly increase susceptibility to breast cancer. Thus, we are also investigating RECQ1 as a modifier of cancer development, progression and chemotherapeutic response.
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Sharma, Sudha