Nicolas Nassar

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.

Peer Reviewed Publications

Seu, Katie G; Trump, Lisa R; Emberesh, Sana; Lorsbach, Robert B; Johnson, Clarissa; Meznarich, Jessica; Underhill, Hunter R; Chou, Stella T; Sakthivel, Haripriya; Nassar, Nicolas N; Seu, Kalani J; Blanc, Lionel; Zhang, Wenying; Lutzko, Carolyn M; Kalfa, Theodosia A  (2020). VPS4A Mutations in Humans Cause Syndromic Congenital Dyserythropoietic Anemia due to Cytokinesis and Trafficking Defects. American journal of human genetics, 107 (6) , 1149-1156More Information

Gasilina, Anjelika; Premnauth, Gurdat; Gurjar, Purujit; Biesiada, Jacek; Hegde, Shailaja; Milewski, David; Ma, Gang; Kalin, Tanya V; Merino, Edward; Meller, Jarek; Seibel, William; Cancelas, José A; Vinnedge, Lisa Privette; Nassar, Nicolas N  (2020). IODVA1, a guanidinobenzimidazole derivative, targets Rac activity and Ras-driven cancer models. PloS one, 15 (3) , e0229801More Information

Liu, Wei; Du, Wei; Shang, Xun; Wang, Lei; Evelyn, Chris; Florian, Maria Carolina; A Ryan, Marnie; Rayes, Ahmad; Zhao, Xueheng; Setchell, Kenneth; Meller, Jarek; Guo, Fukun; Nassar, Nicolas; Geiger, Hartmut; Pang, Qishen; Zheng, Yi  (2019). Rational identification of a Cdc42 inhibitor presents a new regimen for long-term hematopoietic stem cell mobilization. Leukemia, 33 (3) , 749-761More Information

Lee, Lynn H; Gasilina, Anjelika; Roychoudhury, Jayeeta; Clark, Jason; McCormack, Francis X; Pressey, Joseph; Grimley, Michael S; Lorsbach, Robert; Ali, Siraj; Bailey, Mark; Stephens, Philip; Ross, Jeffrey S; Miller, Vincent A; Nassar, Nicolas N; Kumar, Ashish R  (2017). Real-time genomic profiling of histiocytoses identifies early-kinase domain BRAF alterations while improving treatment outcomes. JCI insight, 2 (3) , e89473More Information

San Luis, Boris; Nassar, Nicolas; Carpino, Nick  (2013). New insights into the catalytic mechanism of histidine phosphatases revealed by a functionally essential arginine residue within the active site of the Sts phosphatases. The Biochemical journal, 453 (1) , 27-35More Information

Privette Vinnedge, Lisa M; Kappes, Ferdinand; Nassar, Nicolas; Wells, Susanne I  (2013). Stacking the DEK: from chromatin topology to cancer stem cells. Cell cycle (Georgetown, Tex.), 12 (1) , 51-66More Information

San Luis, Boris; Sondgeroth, Ben; Nassar, Nicolas; Carpino, Nick  (2011). Sts-2 is a phosphatase that negatively regulates zeta-associated protein (ZAP)-70 and T cell receptor signaling pathways. The Journal of biological chemistry, 286 (18) , 15943-54More Information

Jakoncic, Jean; Sondgeroth, Benjamin; Carpino, Nick; Nassar, Nicolas  (2010). The 1.35 A resolution structure of the phosphatase domain of the suppressor of T-cell receptor signaling protein in complex with sulfate. Acta crystallographica. Section F, Structural biology and crystallization communications, 66 (Pt 6) , 643-7More Information

Nassar, Nicolas; Singh, Kavita; Garcia-Diaz, Miguel  (2010). Structure of the dominant negative S17N mutant of Ras. Biochemistry, 49 (9) , 1970-4More Information

Ford, Bradley; Boykevisch, Sean; Zhao, Chen; Kunzelmann, Simone; Bar-Sagi, Dafna; Herrmann, Christian; Nassar, Nicolas  (2009). Characterization of a Ras mutant with identical GDP- and GTP-bound structures . Biochemistry, 48 (48) , 11449-57More Information

Carpino, Nick; Chen, Yunting; Nassar, Nicolas; Oh, Hye-Won  (2009). The Sts proteins target tyrosine phosphorylated, ubiquitinated proteins within TCR signaling pathways. Molecular immunology, 46 (16) , 3224-31More Information

Chen, Yunting; Jakoncic, Jean; Parker, Kathlyn A; Carpino, Nick; Nassar, Nicolas  (2009). Structures of the phosphorylated and VO(3)-bound 2H-phosphatase domain of Sts-2. Biochemistry, 48 (34) , 8129-35More Information

Chen, Yunting; Jakoncic, Jean; Carpino, Nick; Nassar, Nicolas  (2009). Structural and functional characterization of the 2H-phosphatase domain of Sts-2 reveals an acid-dependent phosphatase activity. Biochemistry, 48 (8) , 1681-90More Information

Chen, Yunting; Jakoncic, Jean; Wang, Jin; Zheng, Xiliang; Carpino, Nick; Nassar, Nicolas  (2008). Structural and functional characterization of the c-terminal domain of the ecdysteroid phosphate phosphatase from bombyx mori reveals a new enzymatic activity. Biochemistry, 47 (46) , 12135-45More Information

Mikhailik, Anatoly; Ford, Bradley; Keller, James; Chen, Yunting; Nassar, Nicolas; Carpino, Nick  (2007). A phosphatase activity of Sts-1 contributes to the suppression of TCR signaling. Molecular cell, 27 (3) , 486-97More Information

Xiang, Song; Kim, Eun Young; Connelly, Jessica J; Nassar, Nicolas; Kirsch, Joachim; Winking, Jan; Schwarz, Günter; Schindelin, Hermann  (2006). The crystal structure of Cdc42 in complex with collybistin II, a gephyrin-interacting guanine nucleotide exchange factor. Journal of molecular biology, 359 (1) , 35-46More Information

Kleinman, Holly; Ford, Bradley; Keller, James; Carpino, Nick; Nassar, Nicolas  (2006). Crystallization and initial crystal characterization of the C-terminal phosphoglycerate mutase homology domain of Sts-1. Acta crystallographica. Section F, Structural biology and crystallization communications, 62 (Pt 3) , 218-20More Information

Ford, Bradley; Hornak, Viktor; Kleinman, Holly; Nassar, Nicolas  (2006). Structure of a transient intermediate for GTP hydrolysis by ras. Structure (London, England : 1993), 14 (3) , 427-36More Information

Nassar, Nicolas; Cancelas, Jose; Zheng, Jie; Williams, David A; Zheng, Yi  (2006). Structure-function based design of small molecule inhibitors targeting Rho family GTPases. Current topics in medicinal chemistry, 6 (11) , 1109-16More Information

Ford, Bradley; Skowronek, Karlheinz; Boykevisch, Sean; Bar-Sagi, Dafna; Nassar, Nicolas  (2005). Structure of the G60A mutant of Ras: implications for the dominant negative effect. The Journal of biological chemistry, 280 (27) , 25697-705More Information

Skowronek, Karlheinz R; Guo, Fukun; Zheng, Yi; Nassar, Nicolas  (2004). The C-terminal basic tail of RhoG assists the guanine nucleotide exchange factor trio in binding to phospholipids. The Journal of biological chemistry, 279 (36) , 37895-907More Information

Skowronek, Karlheinz; Ghumman, Mohammed; Zheng, Yi; Nassar, Nicolas  (2003). Crystallization and initial crystal characterization of the N-terminal DH/PH domain of Trio. Acta crystallographica. Section D, Biological crystallography, 59 (Pt 7) , 1273-5More Information

Smith, William James; Nassar, Nicolas; Bretscher, Anthony; Cerione, Richard A; Karplus, P Andrew  (2003). Structure of the active N-terminal domain of Ezrin. Conformational and mobility changes identify keystone interactions. The Journal of biological chemistry, 278 (7) , 4949-56More Information

Hall, Brian E; Bar-Sagi, Dafna; Nassar, Nicolas  (2002). The structural basis for the transition from Ras-GTP to Ras-GDP. Proceedings of the National Academy of Sciences of the United States of America, 99 (19) , 12138-42More Information

Hegde, Shailaja; Gasilina, Anjelika; Wunderlich, Mark; Lin, Yuan; Buchholzer, Marcel; Krumbach, Oliver H F; Akbarzadeh, Mohammad; Ahmadian, Mohammad Reza; Seibel, William; Zheng, Yi; Perentesis, John P; Mizukawa, Benjamin E; Vinnedge, Lisa Privette; Cancelas, José A; Nassar, Nicolas N  (2022). Inhibition of the RacGEF VAV3 by the small molecule IODVA1 impedes RAC signaling and overcomes resistance to tyrosine kinase inhibition in acute lymphoblastic leukemia. Leukemia, 36 (3) , 637-647More Information