Assistant Professor
Biochemistry and Molecular Biology Department, Johns Hopkins Bloomberg School of Public Health

RESEARCH OVERVIEW

Intrinsic or acquired resistance to targeted therapy underlies most breast cancer-induced mortality. Dr. Nayar recently identified a subset of estrogen receptor-positive (ER+) breast cancer that is resistant to ER-targeted therapy through the acquisition of mutations in the growth factor molecule HER2. The Nayar laboratory aims to understand the underlying mechanism(s) by which a tumor becomes resistant to targeted therapy, employing breast cancer as a model. In particular, the lab is interested in mechanisms underlying the emergence and maintenance of resistant subpopulations within tumors, genetic and epigenetic drivers of resistance, and the identification of new therapeutic vulnerabilities in targeted 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 targeted inhibitors in advanced metastatic breast cancer.

Cancer Biology | Cell Biology | Cellular Stress and Cell Signaling | Genetics, Genomics and Gene Regulation | Translational Research

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.

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