Our lab is housed on the third floor of Ben and Maytee Fisch College of Pharmacy (FCOP) (WT Brookshire Building) at The University of Texas, Tyler. Our research is centered on drug discovery with a focus on discovering new allosteric agents that can be developed into novel medications. Current projects involve several targets involved in cancer and bacterial resistance. We use several techniques including, but not limited to, virtual and high throughput screening of compound libraries, protein expression and purification, coupled kinase in vitro assays, cell-based assays, immunofluorescence and immunoblots and biophysical assays
Project 1: HER2 receptor is a clinically validated target implicated in many malignancies. A critical step in its activation is dimerization of its two kinase domains which starts the autophosphorylation and initiates the signaling cascade. Current therapies are effective with only a subset of patients in only limited cancers and emerging resistance is making them even less effective. This project’s main goal is to discover allosteric inhibitors that target HER2 homodimerization via a novel mechanism of action by inhibiting dimerization of the receptor kinase domains.
Project 2: Dimerization of HER family receptors (EGFR, HER2, HER3 and HER4) occurs in vivo after ligand activation or with overexpression that occurs in cancer cell membranes. The dimerization in vitro is mainly concentration-dependent and can be induced by local concentration on artificial membrane of Nickel liposomes. The assay is hard to implement and reproduce due to the high variability in liposome size, lipid concentration and local kinase domain concentration on the liposome surface. Our lab is attempting a protein engineering project to express and purify the receptors kinase domains capable of self-association into well-defined dimers in solution. Applications will be geared to assay design and inhibitor drug discovery efforts.
Project 3: Studying the molecular underpinning of bacterial resistance is vital for prevention of antibiotic resistance. Our lab, in collaboration with Dr. Aurijit Sarkar lab in High Point University, is working towards studying several kinase targets involved in emergence of resistance. We aim to decipher how resistance attributed to these kinases develop in bacteria and discover agents that can be used as Resistance Modifying Agents to curb antibiotic resistance and increase the efficacy of current antibiotics.