Utthara Nayar Lab

Intrinsic or acquired resistance to anti-cancer therapies underlies most mortality from breast and ovarian cancers. The Nayar Laboratory aims to understand the underlying mechanisms 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 a models. 

In particular, the Lab is interested mapping cancer-associated genetic variants to function and phenotype, uncovering the genetic and epigenetic drivers of resistance, and identifying new therapeutic vulnerabilities in targeted therapy-resistant tumors. We focus on a new subset of estrogen receptor-positive (ER+) breast cancer identified in 2019 that is resistant to ER-targeted therapy through the acquisition of mutations in growth factor pathways. 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.

Yayli, G, Tokofsky, A, Nayar, U. The intersection of the HER2-low subtype with endocrine resistance: the role of interconnected signaling pathways. Frontiers in Oncology, 2024.

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.