Research Profile
A wide range of molecules has been shown to be important for cellular migration. Unfortunately, in cancer, many regulatory processes are aberrant and lead to highly invasive cell behavior and metastasis. In particular, the proteins of the Rho GTPase family, RhoA, Cdc42 and Rac, are most prominently known to be crucial for cell migration and other processes related to cancer invasion. The focus of our research is to understand how spatial and temporal regulation of Rho GTPase activity is organized during cellular migration and how such mechanisms are altered in cancer. To achieve this, we are using fluorescence biosensor imaging to visualize localized GTPase activity in living cells. The combination of these tools with other contemporary cell biological methods such as siRNA technology is a powerful means to dissect how the complex network of upstream regulators affects localized Rho protein signaling and how this is translated into normal as well as aberrant cell migration.

Selected Publications

Machacek M, Hodgson L, Welch C, Elliott H, Pertz O, Nalbant P, Abell A, Johnson GL, Hahn KM, Danuser G. Coordination of Rho GTPase activities during cell protrusion. Nature 2009;461(7260):99-103.

Nalbant P, Chang YC, Birkenfeld J, Chang ZF, Bokoch GM. Guanine nucleotide exchange factor-H1 regulates cell migration via localized activation of RhoA at the leading edge. Mol Biol Cell 2009;20(18):4070-82.

Manukyan M, Nalbant P, Luxen S, Hahn KM, Knaus UG. RhoA GTPase activation by TLR2 and TLR3 ligands: connecting via Src to NF-kappa B. J Immunol 2009;182(6):3522-9.

Chang YC, Nalbant P, Birkenfeld J, Chang ZF, Bokoch GM. GEF-H1 Couples Nocodazole-induced Microtubule Disassembly to Cell Contractility via RhoA. Molecular Biology of the Cell 2008;19(5):2147-53.

Lim Y, Lim ST, Tomar A, Gardel M, Bernard-Trifilo JA, Chen XL, Uryu SA, Canete-Soler R, Zhai J, Lin H, Schlaepfer WW, Nalbant P, Bokoch G, Ilic D, Waterman-Storer C, Schlaepfer DD. PyK2 and FAK connections to p190Rho guanine nucleotide exchange factor regulate RhoA activity, focal adhesion formation, and cell motility. Journal of Cell Biology 2008;180(1):187-203.

Frantz C, Karydis A, Nalbant P, Hahn KM, Barber DL. Positive feedback between Cdc42 activity and H+ efflux by the Na-H exchanger NHE1 for polarity of migrating cells. Journal of Cell Biology 2007;179(3):403-10.

El-Sibai M, Nalbant P, Pang H, Flinn RJ, Sarmiento C, Macaluso F, Cammer M, Condeelis JS, Hahn KM, Backer JM. Cdc42 is required for EGF-stimulated protrusion and motility in MTLn3 carcinoma cells. Journal of Cell Science 2007;120:3465-3474.

Birkenfeld J, Nalbant P, Bohl BP, Pertz O, Hahn KM, Bokoch GM. GEF-H1 modulates localized RhoA activation during cytokinesis under the control of mitotic kinases. Developmental Cell 2007;12(5): 699-712.

Zhao T, Nalbant P, Mikio Hoshino, and Bokoch GM. Signaling requirements for P-Rex1 translocation, a key Rac2 exchange factor involved in chemoattractant-stimulated human neutrophil function. Journal of Leukocyte Biology 2007;81(4):1127-36.

Dehmelt L, Nalbant P, Steffen W, Halpain S. A microtubule-based, dynein-dependent force induces local cell protrusions: Implications for neurite initiation. Brain Cell Biology 2006;35(1):39-56. Epub 2007 Mar 13.

Belvindrah R, Nalbant P, Ding S, Wu C, Bokoch GM, Mueller U. Integrin-linked kinase regulates Bergmann glial differentiation during cerebellar development. Molecular and Cellular Neuroscience 2006;33(2):109-25.

Hodgson L, Nalbant P, Shen F, Hahn K. Imaging and Photobleach Correction of Mero-CBD, Sensor of Endogenous Cdc42 Activation. Methods in Enzymology 2006;406:140-56.

Subauste MC, Nalbant P, Adamson ED, Hahn KM. Vinculin controls PTEN protein level by maintaining the interaction of the adherens junction protein beta-catenin with the scaffolding protein MAGI-2. Journal of Biological Chemistry 2005;280(7):5676-81.