Nicolas Nassar, PhD

Member, Division of Experimental Hematology & Cancer Biology
Associate Professor, UC Department of Pediatrics

nicolas.nassar@cchmc.org

About

Biography

My areas of research interest include drug development and signaling with focus on small GTPases. My research is both basic and translational.

My research efforts encompass several methodologies, including protein crystallography, biophysical and biochemical studies, cellular functional assays, and ultimately, identifying small molecule compounds that bind to and modulate GTPase signaling in in vivo models of cancer.

Rac GTPases are key regulators of cell growth. By reorganizing the actin cytoskeleton in response to extracellular cues, Rac GTPases play a key role in cancer cell metastasis. My lab's goal is to understand the regulation of Rac and its role in cancer. More specifically, my work aims to find ways to inhibit its hyperactivation in leukemia.

One of my lab’s groundbreaking discoveries is the identification of a small molecule inhibitor of Vav3, a Rac activator. Our research aims to unravel the mechanism of action of the Vav3-inhibitor. In addition, our small molecule technology has been submitted to the US Patent Office.

My research has been published in PLoS ONE, Leukemia, JCI Insight, and Oncogene: Including Oncogene Reviews. I have been a researcher for more than 20 years and began working at Cincinnati Children’s in 2010.

PhD: University Joseph Fourier, Grenoble,France, 1992.

Postdoc: Max Plank Institut, Dortmund, Germany, 1996.

Research Associate: Cornell University, Ithaca, NY, 2000.

Assistant Professor: Stony Brook University, NY, 2006.

Research Assistant Professor: Stony Brook University, Stony Brook, NY, 2010.

Research Areas

Experimental Hematology and Cancer Biology, Cancer and Blood Diseases

Publications

Selected

Merlin tumor suppressor function is regulated by PIP2-mediated dimerization. Hennigan, RF; Thomson, CS; Stachowski, K; Nassar, N; Ratner, N. PloS one. 2023; 18:e0281876.

Selected

VPS4A Mutations in Humans Cause Syndromic Congenital Dyserythropoietic Anemia due to Cytokinesis and Trafficking Defects. Seu, KG; Trump, LR; Emberesh, S; Lorsbach, RB; Johnson, C; Meznarich, J; Underhill, HR; Chou, ST; Sakthivel, H; Nassar, NN; Seu, KJ; Blanc, L; Zhang, W; Lutzko, CM; Kalfa, TA. The American Journal of Human Genetics. 2020; 107:1149-1156.

Selected

IODVA1, a guanidinobenzimidazole derivative, targets Rac activity and Ras-driven cancer models. Gasilina, A; Premnauth, G; Gurjar, P; Biesiada, J; Hegde, S; Milewski, D; Ma, G; Kalin, TV; Merino, E; Meller, J; Seibel, W; Cancelas, JA; Vinnedge, LP; Nassar, NN. PloS one. 2020; 15:e0229801.

Selected

Rational identification of a Cdc42 inhibitor presents a new regimen for long-term hematopoietic stem cell mobilization. Liu, W; Du, W; Shang, X; Wang, L; Evelyn, C; Florian, MC; Ryan, MA; Rayes, A; Zhao, X; Setchell, K; Nassar, N; Geiger, H; Pang, Q; Zheng, Y. Leukemia. 2019; 33:749-761.

Selected

Breast cancer-associated missense mutants of the PALB2 WD40 domain, which directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair. Park, J; Singh, TR; Nassar, N; Zhang, F; Freund, M; Hanenberg, H; Meetei, AR; Andreassen, PR. Oncogene: Including Oncogene Reviews. 2014; 33:4803-4812.

Selected

Direct inhibition of retinoblastoma phosphorylation by nimbolide causes cell-cycle arrest and suppresses glioblastoma growth. Karkare, S; Chhipa, RR; Anderson, J; Liu, X; Henry, H; Gasilina, A; Nassar, N; Roychoudhury, J; Clark, JP; Kumar, A; Pauletti, GM; Ghosh, PK; Dasgupta, B. Clinical Cancer Research. 2014; 20:199-212.

Selected

New insights into the catalytic mechanism of histidine phosphatases revealed by a functionally essential arginine residue within the active site of the Sts phosphatases. San Luis, B; Nassar, N; Carpino, N. The Biochemical journal. 2013; 453:27-35.

Selected

Sts-2 is a phosphatase that negatively regulates zeta-associated protein (ZAP)-70 and T cell receptor signaling pathways. San Luis, B; Sondgeroth, B; Nassar, N; Carpino, N. The Journal of biological chemistry. 2011; 286:15943-15954.

Selected

The 1.35 A resolution structure of the phosphatase domain of the suppressor of T-cell receptor signaling protein in complex with sulfate. Jakoncic, J; Sondgeroth, B; Carpino, N; Nassar, N. Acta Crystallographica. Section F: Structural Biology Communications. 2010; 66:643-647.

Selected

Structure of the dominant negative S17N mutant of Ras. Nassar, N; Singh, K; Garcia-Diaz, M. Biochemistry. 2010; 49:1970-1974.