The current focus of the Institute centers on signaling by protein kinases. Protein kinases catalyze the following reaction: 

MgATP^1- + protein-OH  → Protein-OPO₃^2- + MgADP + H⁺. 

Based upon the nature of the phosphorylated –OH group, these enzymes are classified as protein-serine/threonine kinases and protein-tyrosine kinases. Investigators have identified 478 typical and 40 atypical protein kinase genes in humans (total 518) that correspond to about 2% of all human genes. The family includes 385 protein-serine/threonine kinases, 90 protein-tyrosine kinases, and 43 protein-tyrosine-kinase like proteins. Of the 90 protein-tyrosine kinases, a total of 58 are receptor and 32 are non-receptor in nature. The exons of the protein kinase family account for about 1.3 Mb or 2% the entire coding sequence of human DNA. The protein kinase family is the second largest enzyme family (after proteases) and the fifth largest gene family in humans.

Previous work considered the role of the Bcr-Abl protein kinase and its role in producing chronic myelogenous leukemia. Other studies have centered on the epidermal growth factor receptor family including HER1, HER2, HER3, and HER4 (Human Epidermal growth factor Receptors). More recent work has focused in the Src family of protein kinases and the stem cell factor protein kinase called Kit. 

Current studies are addressing  the role of vascular endothelial growth factor and its receptors in the treatment of cancers. When tumors reach a size of about 0.2–2.0 mm in diameter, they become hypoxic and limited in size in the absence of angiogenesis. In order to increase in size, tumors undergo an angiogenic switch where the action of pro-angiogenic factors predominates, resulting in angiogenesis and tumor progression. One mechanism for driving angiogenesis results from the increased production of vascular endothelial growth factor (VEGF). This factor activates two VEGF protein-tyrosine kinase receptors (VEGFR1 and VEGFR2). Owing to the importance of angiogenesis in tumor progression, inhibition of VEGF signaling represents an attractive cancer treatment. 

The U.S. Food and Drug administration approved sorafenib (Nexavar) monotherapy for the treatment of metastatic renal cell carcinoma in December 2005. Sorafenib inhibits several protein kinases including VEGFR2, VEGFR3, Flt-3, Kit, PDGFR-b, and Raf. Moreover, the U.S. Food and Drug Administration approved sunitinib (Sutent) monotherapy for the treatment of (i) metastatic renal cell carcinoma and (ii) gastrointestinal stromal tumors (GIST) in January 2006. Sunitinib inhibits several receptor protein-tyrosine kinases including VEGFR1, VEGFR2, VEGFR3, colony-stimulating factor-1 receptor, Flt-3, platelet-derived growth factor receptors (a and b), and Kit, the stem cell factor receptor. The therapeutic mechanism of action of sorafenib and sunitinib appears to be related to their inhibition of angiogenesis. 

Our current goal is to elucidate the signaling pathways that are activated by the VEGF receptor protein-tyrosine kinases. These downstream pathways include phospholipase C-γ, phosphatidylinositol 3-kinase, protein kinase B/Akt, and protein kinase C. Moreover, several adaptor proteins (Shc, Grb2, and Gab1) play an essential role in VEGF signaling.