A photo of Nicolas Nassar.

Nicolas Nassar, PhD


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

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.

Publications

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; et al. 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; et al. PLoS ONE. 2020; 15.

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; et al. 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. 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; et al. Clinical Cancer Research. 2014; 20:199-212.

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. 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 and Crystallization 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.

Selected

Characterization of a Ras mutant with identical GDP- and GTP-bound structures. Ford, B; Boykevisch, S; Zhao, C; Kunzelmann, S; Bar-Sagi, D; Herrmann, C; Nassar, N. Biochemistry. 2009; 48:11449-11457.

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