Utthara Nayar
Targeting resistant breast and ovarian cancer
Assistant Professor
Department of Biochemistry and Molecular Biology
Bloomberg School of Public Health
Research Overview
Intrinsic or acquired resistance to anti-cancer therapies underlies most mortality from breast and ovarian cancers. Dr. Nayar identified a new subset of breast cancer that develops resistance to endocrine therapy through the acquisition of mutations in receptor tyrosine kinases (RTKs), such as HER2 and FGFR. The Nayar laboratory aims to understand the underlying molecular mechanism(s) by which a tumor becomes resistant to targeted therapy through the acquisition of genetic alterations, employing ER+ breast and low-grade serous ovarian cancer as models. In particular, the lab is interested in mapping cancer-associated genetic variants to function and phenotype, uncovering the genetic and epigenetic drivers of resistance, and identifying new therapeutic vulnerabilities in therapy-resistant tumors. To this end, the laboratory leverages cell and molecular biology, animal models, functional genomics tools, and high-throughput screening methodologies to understand resistance to endocrine and targeted inhibitors in advanced metastatic breast and ovarian cancer.
Selected Publications
- Qi M, Nayar U, Ludwig LS, Wagle N, Rheinbay E. cDNA-detector: detection and removal of cDNA contamination in DNA sequencing libraries. BioMed Central Bioinformatics, 2021.
- Persky NS, Hernandez D, Do Carmo M, Brenan L, Cohen O, Kitajima S, Nayar U, Walker A, Pantel S, Lee Y, Cordova J, Sathappa M, Zhu C, Hayes TK, Ram P, Pancholi P, Mikkelsen TS, Barbie DA, Yang X, Haq R, Piccioni F, Root DE, Johannessen CM. Defining the landscape of ATP-competitive inhibitor resistance residues in protein kinases. Nature Structural & Molecular Biology, 2020.
- Nayar U, Cohen O, Kapstad C, Cuoco MS, Waks AG, Wander SA, Painter C, Freeman S, Persky NS, Marini L, Helvie K, Oliver N, Rozenblatt-Rosen O, Ma CX, Regev A, Winer EP, Lin NU, Wagle N. Acquired HER2 mutations in ER+ metastatic breast cancer confer resistance to estrogen receptor-directed therapies. Nature Genetics, 2019.
- Nayar U, Sadek J, Reichel J, Hernandez-Hopkins D, Akar G, Barelli PJ, Sahai MA, Zhou H, Totonchy J, Jayabalan D, Niesvizky R, Guasparri I, Hassane D, Liu Y, Sei S, Shoemaker RH, Warren JD, Elemento O, Kaye KM, Cesarman E. Identification of a nucleoside analog active against adenosine kinase-expressing plasma cell malignancies. Journal of Clinical Investigation, 2017.
- Nayar U, Lu P, Goldstein RL, Vider J, Ballon G, Rodina A, Taldone T, Erdjument-Bromage H, Chomet M, Blasberg R, Melnick A, Cerchietti L, Chiosis G, Wang YL, Cesarman E. Targeting the Hsp90-associated viral oncoproteome in gammaherpesvirus-associated malignancies. Blood, 2013.