Development of DNA-based pathogen testing platforms for the health, cannabis, food and agriculture industries. Tests involve multiplex PCR and DNA microarray technology with reliable high-throughput capabilities. Projects completed: Live-Dead Assay (Microbial detection assay), DetectX-RV (COVID Diagnostic Assay). Current project is a COVID variant identification assay. My responsibilities include project management, routine literature review to stay current with technology and maintain competitive products, experimental design and execution of experiments, management/mentorship of junior scientists, data analysis/interpretation, data reporting, protocol development (SOP), document control, development of quality control data, CLIA lab work, CLIA reporting, and successful collaborations with companies and universities. Key Accomplishments include FDA-EUA approval of DetectX-RV, 2 patents, 2 launched products, 1 white paper.

1) Development of automated high throughput cell based assays to assist in drug discovery of PAR2 specific compounds. 2) In vivo testing of compound leads in a murine asthma model to determine efficacy of drugs in reducing asthma indicators. 3) Identified inflammatory and pro-migration cytokines secreted from human airway epithelial cell cultures grown at air-liquid interface in response to allergen (A. alternata) exposure.

Our laboratory focuses on Protease Activated Receptor 2 (PAR2), a G-protein coupled receptor that possesses the unique ability to self-activate upon proteolysis of the extracellular domain. This event exposes an activating peptide sequence that has guided drug discovery efforts in combating associated inflammatory diseases such as allergic asthma, chronic pain, arthritis and cancer. A primary focus of drug design has been to develop peptides or peptidomimetic ligands that can specifically bind PAR2 to: 1) invoke full activation in the absence of protease cleavage; 2) invoke full inhibition in the presence of proteolytic cleavage, or to; 3) induce biased signaling to best shape physiological response. Recently, our lab discovered the first potent (IC50 < 5 mM) full PAR2 inhibitor, C391 that can block PAR2-dependent signaling pathways invoked by peptidomimetics or protease agonists in vitro, and pain pathways in vivo. Using C391 as a template, we initially focused our drug discovery efforts towards developing a bioavailable, low molecular weight potent PAR2 inhibitor. We tested several smaller, but structurally similar, C391 derivatives for their ability to block PAR2 dependent signaling. Inhibition is retained, albeit slightly reduced, following removal of the tyrosine moiety from C391. These initial results provide key structure activity relationships that continue to provide new drug candidates in search of efficacious PAR2 drugs.

The cancer therapeutic target, HSP90 is a molecular chaperone essential for aberrant protein stability and function in cancerous cells. To elucidate the role of HSP90 inhibition in treating cancer, my research focus was to evaluate the impact of HSP90 inhibitors on the conformation and function of HSP90 in tumor models. This included assessing the anti-cancer efficacy of a novel dual MET and HSP90 inhibitor. MET, a receptor tyrosine kinase and HSP90 client was found to be mutated and overexpressed in gastric, lung and breast cancer. Collaborative work afforded me a co-authorship on the finding that a MET tyrosine kinase inhibitor coupled with an HSP90 inhibitor presents a novel and synergistic approach to increasing proteasome-dependent apoptosis in cancer cells to overcome TKI resistance. Close examination of tumor cell toxicity, inhibition of downstream signaling products, migration/invasion inhibition and P-MET inhibition via in-vitro kinase assay suggests this novel MET and HSP90 inhibitor has similar therapeutic potential for the treatment of MET-directed tumors and crizotinib-resistant MET tumors.