Utthara Nayar, PhD

Dr. Nayar is currently an Assistant Professor in the Department of Biochemistry and Molecular Biology in the Bloomberg School of Public Health at Johns Hopkins University (JHU). She holds a joint appointment in the Cancer Invasion and Metastasis Program in the JHU School of Medicine, and is also a member of the Breast and Gynecologic Malignancies Program at the Sidney Kimmel Comprehensive Cancer Center at JHU.

https://www.linkedin.com/in/uttharanayar/

• Dr. Nayar receives the 2024 AACR Victoria's Secret Global Fund for Women's Cancers Career Development Award, in partnership with Pelotonia and AACR (2025)
• Dr. Nayar receives the 2023 Rivkin Pilot Award, Ovarian Cancer Research Alliance (2023)
• Utthara Nayar Joins BMB Faculty, Johns Hopkins Bloomberg School of Public Health (2021)
• Dr. Nayar's podcast on "Evolving mutations in metastatic breast cancer",  BreastCancer.org (2018)
• Dr. Nayar's research highlighted as one of four stories of interest at Press Preview before AACR Annual Meeting 2018, American Association for Cancer Research (March 15, 2018)
• Featured interview "Utthara Nayar is targeting cancer drug resistance", Broad Institute of MIT and Harvard (March 19, 2018)

Joint Appointment in Oncology

Therapeutic response and resistance in breast and ovarian cancer

Nayar Lab - Lab Website

• The Nayar laboratory is focused on the biology of therapeutic resistance in breast cancer. Dr. Nayar recently identified a subset of estrogen receptor-positive (ER+) metastatic breast cancer that is resistant to ER-targeted therapy by acquiring mutations in the growth factor molecule HER2. The laboratory aims to understand the mechanism(s) by which a tumor becomes resistant to targeted therapy, employing this subset of breast cancer as a model.

The primary reason for breast cancer mortality is the development of endocrine resistance, through largely unknown mechanisms, to therapies targeting the estrogen receptor. Endocrine resistance is also an emerging problem in the treatment of ER-expressing ovarian cancer. Dr. Nayar identified a novel class of clinical endocrine resistance, designated “MAPK-active” tumors, that account for ~13-20% of resistant breast tumors. This finding was highlighted as one of the top four stories of interest at the AACR Annual Meeting in 2018, and the incidence of these therapeutically-intractable tumors continues to rise in the clinic. The scientific objective of Dr. Nayar’s research program is to study tumor cell-intrinsic signaling, transcriptional rewiring and phenotypic plasticity, tumor evolution and acquired therapeutic vulnerabilities, and the tumor (+immune) microenvironment of therapy-resistant breast and ovarian cancer. Towards this end, the lab uses cell, molecular, animal model, and large-scale multi-omic approaches to understand the mechanistic basis of resistance, with a view to enabling future clinical translation and improving patient outcomes.

https://scholar.google.com/citations?hl=en&user=l1wu0bkAAAAJ

• Nayar, U, Cohen, O, Kapstad, CJ, Waks, A, Wander, S, Marini, L, Helvie, K, Oliver, N, Persky, N, Painter, C, Freeman, S, Lin, NU, Winer, EP, Ma, CX, Wagle, N. Acquired HER2 mutations in ER+ metastatic breast cancer confer resistance to ER-directed therapies. Nature Genetics. 2019 Feb 1; 51(2): 207-216

• 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, R, Warren, DW, Elemento, O, Kaye, KM, Cesarman, E. Identification of a nucleoside analog active against adenosine kinase-expressing plasma cell malignancies. Journal of Clinical Investigation. 2017 Jun 1; 127(6): 2066-2080. (PMID: 28504647)

• Mao, P, Cohen, O, Kowalski, KJ, Kusiel, JG, Buendia-Buendia, JE, Cuoco, MS, Exman, P, Wander, SA, Waks, AG, Nayar, U, Chung, J, Freeman, S, Rozenblatt-Rosen, O, Miller, VA, Piccioni, F, Root, DE, Regev, A, Winer, EP, Lin, NU, Wagle, N. Acquired FGFR and FGF alterations confer resistance to estrogen receptor (ER) targeted therapy in ER+ metastatic breast cancer. Clinical Cancer Research. 2020 Nov 15;26(22):5974-5989

• 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, T, Pancholi, P, Ram, P, Mikkelsen, TS, Barbie, DA, Yang, X, Haq, R, Piccioni, F, Root, D, Johannessen, CM. Defining the landscape of ATP-competitive inhibitor resistance residues in protein kinases. Nature Structural and Molecular Biology. 2020 Jan 10; 27: 92-104

• Wander, SA, Cohen, O, Gong, X, Johnson, GN, Buendia-Buendia, JE, Lloyd, MR, Kim, D, Luo, F, Mao, P, Helvie, K, Kowalski, KJ, Nayar, U, Waks, AG, Parsons, SH, Martinez, R, Litchfield, LM, Ye, XS, Yu, C, Jansen,VM, Stille, JR, Smith, PS, Oakley, GJ, Chu, QS, Batist, G, Hughes, ME, Kremer, JD, Garraway, LA, Winer, EP, Tolaney, SM, Lin, NU, Buchanan, SG, Wagle, N. The genomic landscape of intrinsic and acquired resistance to cyclin-dependent kinase 4/6 inhibitors in patients with hormone receptor-positive metastatic breast cancer. Cancer Discovery. 2020 Aug;10(8):1174-1193

• Introduction to Cancer Biology, Johns Hopkins University Bloomberg School of Public Health, 120.625.81
• Cancer Biology, Johns Hopkins University Bloomberg School of Public Health, 120.624.01, 3/24/21 - 5/19/21
• Special Studies- Current Topics in BMB, Johns Hopkins University Bloomberg School of Public Health, 120.872.01

Novel nucleoside analogs and use thereof in therapeutic treatment.,

This invention describes potential use of a family of nucleoside analogs in malignancies expressing adenosine kinase (ADK), in particular plasma cell tumors such as KSHV+ primary effusion lymphoma (PEL), and multiple myeloma (MM). The family of compounds described is under further preclinical testing for selected incurable plasma cell malignancies, and may move on to clinical trials pending safety and efficacy profiling. I characterized the compound from a screen, determined the mechanism of activation (phosphorylation by ADK) using genomics and in vitro studies- which led to the identification of ADK as a biomarker for response- and performed preclinical studies to demonstrate potent efficacy in mouse models of PEL.

PCT/US2017/027590

• Women in Cancer Research Scholar Award, American Association for Cancer Research
• Ruth L. Kirschstein National Research Service Award, National Institutes of Health
• ASH Abstract Achievement Award, American Society of Hematology
• AACR-Aflac,Inc. Scholar-in-Training Award, American Association for Cancer Research
• NCI Transition Career Development Award (K22), National Cancer Institute/ National Institutes of Health

• A purine scaffold Hsp90 inhibitor has antitumor activity in KSHV-associated malignancies by suppressing vFLIP, Oral Presentation, AACR Annual Meeting 2012, American Association for Cancer Research
• Acquired HER2 mutations in ER+ metastatic breast cancer confer resistance to ER-directed therapies, Oral Presentation, AACR Annual Meeting 2018, American Association for Cancer Research
• Identification of a Novel Inhibitor That Selectively Targets NF-Œ∫B Activity in KSHV-Infected Lymphoma Cells, Oral Presentation, ASH Annual Meeting 2012, American Society of Hematology

Biochemistry and Molecular Biology

Biochemistry, Cellular and Molecular Biology

• American Association for Cancer Research,

  Associate Member

Diversity and Inclusion Committee, Member, 9/8/20