Nicolas Nassar, PhD

Member, Division of Experimental Hematology & Cancer Biology

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-6597

Fax 513-636-3549


The major focus of our laboratory is to understand the regulation and signaling of the GTP-binding protein Ras and other Ras-like GTPases and to find small molecules that inhibit their activity in human cancers. Signaling by Ras-like GTPases is key to almost every cellular process and Ras is among the most mutated genes in human cancer. Despite this, a small molecule specifically targeting Ras activity has yet to enter clinical trials. Our research efforts encompass several methodologies, including protein crystallography, biophysical and biochemical studies, cellular functional assays, and ultimately, high throughput screenings of chemical libraries of small compounds that bind to and modulate GTPase signaling in cell line models.

We have identified several compounds that bind in vitro to Ras, inhibit cell proliferation of lung and other Ras-transformed cell lines, and decrease the activation of Erk-1/-2 and PI3K/AKT. Several ongoing questions stem from this finding: (i) we want to establish the mechanism of action(s) of these compounds. What gene or cellular process do they activate or silence downstream of Ras? Do they bind to Ras in cells and how specific is their binding? (ii) We are in the process of translating our findings to several disease models where Ras is hyperactivated, including both solid tumors such as lung adenocarcinomas, and MPNSTs and leukemias such as B-ALL.

We are also interested in the structure/function relationship of the multidomain protein tyrosine phosphatase (PTP) UBASH3B/Sts-1. Sts-1 was shown to be a target in triple negative breast cancer (TNBC). Our research is geared towards identifying small molecule inhibitors of the phosphatase activity of Sts-1. We have identified one such compound that inhibits the phosphatase activity of Sts-1 in vitro, decreases TNBC cell proliferation and decreases overall levels of phosphorylated proteins. We are currently testing structural analogs of our lead compound to further improve its potency.

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.

Jackoncic J, Sondgeroth B, Carpino N, Nassar N. The 1.35 Å structure of the Phosphatase domain of the Suppressor of T Cell Receptor Signaling Protein in complex with Sulfate. Acta Cryst section F66, 2010  643-647.

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

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

Carpino N, Chen Y, Nassar N, Hye-Won Oh. The Sts proteins target tyrosine phosphorylated, ubiquitinated proteins within TCR signaling pathways. in review. J. Immuno. 2009  46,3224-3231.

Chen Y, Jakoncic J, Parker KA, Carpino N, Nassar N. Structures of the Phosphorylated and VO3-bound 2H-Phosphatase Domain of Sts-2. Biochemistry. 2009  48, 8129-8135.

Chen Y, Jakoncic J, Carpino N, Nassar N. Structural and Functional Characterization of the 2H-phosphatase domain of Sts-2 reveals an Acid-Dependent Phosphatase Activity. Biochemistry. 2009  48,1681-1690.

Chen Y, Jakoncic J, Keller J, Wang J, Zheng X, Carpino N, Nassar N. Structural and functional characterization of the C-terminal domain of the ecdysteroid phosphate phosphatase from Bombyx mori. Biochemistry. 2008  47,12135-12145.

Mikhailik A, Ford B, Keller J, Chen Y, Nassar N, Carpino N. The C-terminal mutase-like domain of Sts-1 is important for its T-cell suppressor activity. Molecular Cell. 2007  27, 486-487.