Scottsdale, Arizona, United States
Supporting advanced human cellular inflammation projects in the respiratory pipeline and early target discovery for small molecules and biologics for the treatment of inflammatory diseases. Executing various research projects, tasks and assignments under none or very limited supervision: - Developed a PD assay to measure inflammatory biomarkers in whole blood, which was successfully run in the Phase I Study of RG7258 - a humanized monoclonal antibody designed to inhibit binding of TSLP to its receptor TSLP-R in uncontrolled asthma. - Instrumentally supported advanced programs for planning a design and for running the Phase I Study of RG7185 - a small molecule antagonist of the CRTH2 receptor in asthma. - Developed the expertise in the immuno-pharmacological assessment of functionalities and properties of human peripheral blood cells using an imaging flow cytometry - the ImageStreamX Technology (Amnis Corp.) - e.g.: antibody mediated target internalization, sub-cellular organelle co-localization, receptor trafficking, quantitation of apoptosis. - Gained advanced and extensive experience in developing and implementing scientific assays (e.g.: imaging flow cytometry, radioligand binding and kinetics, GTPgammaS, calcium flux-FLIPR, chemokine-cytokine release - Luminex/MSD/ELISA, whole blood chemotaxis, cAMP) to define pharmacology of various receptors, and new chemical and biological entities to advance them into clinical development (e.g.: RG7258 and RG7185, both Phase I).
Cellular pharmacology studies to advance the discovery of novel small molecules for the treatment of inflammatory disorders: - Developed and conducted the majority of the in vitro pharmacology which advanced the novel CXCR2 antagonist, Sch527123, to candidate nomination (Gonsiorek et al JPET, 2007; Chapman et al JPET, 2007; Dwyer et al J Med Chem, 2006; Yu et al Bioorg Med Chem Lett, 2008). - Pharmacological characterization of CCR5 allosteric inhibitors (Maraviroc, Aplaviroc and Viriviroc) (Stritzki et al Antimicrob Agents Chemother, 2005). - Characterized the pharmacology of inverse agonist at the peripheral cannabinoid receptor resulting in 2001 Schering-Plough President's Award for Discover for Outstanding Scientific and Technical Achievement (Gonsiorek et al BJP, 2007; Gonsiorek et al JBC, 2006; Shankar et al Bioorg Med Chem Lett, 2005; Gonsiorek et al Mol Pharm, 2000). - Developed chemotaxis assay of freshly isolated human monocytes. - Developed assays (radioligand binding, [35S]GTPgammaS, FLIPR calcium flux and membrane potential, cAMP, autoradiography, HSP27 MAPKAP Kinase 2 phosphorylation) and cell lines for HTS and target pharmacology of various chemokine, lipid and peptide receptors. - Developed high throughput leukocyte chemotaxis and non-equilibrium binding assays ±98% plasma as a critical decision gate for compound progression into in vivo testing.
Designing, executing and analyzing experiments concerning signal transduction pathways, modulation of G-protein coupled receptors, and drug-receptor interactions.