San Diego, California, United States
Passionate scientist and leader with ~16 years of experience in small molecule drug discovery. Proven track record of advancing programs from hit identification through candidate nomination across diverse therapeutic modalities. Expertise in leveraging both traditional and emerging hit-ID strategies and integrating mechanistic insights with translational goals to drive impactful drug discovery. Recognized for scientific leadership and cross-functional collaboration, with a strong commitment to mentoring and developing talent. Actively coach and guide scientists across disciplines, fostering a culture of innovation, scientific rigor, and continuous learning.
Leading a group of PhD and non-PhD scientists to routinely support Oncology small molecule and ADC drug discovery programs in 3 key areas: 1. Hit-ID: Using traditional biochemical, cell-based & phenotypic as well as now routine biophysical methods like DEL, ASMS, biophysical proximity methods to identify novel chemical matter supporting modalities like small-molecule inhibitors, TBMs for PROTACs, Molecular Glues, Monovalent Degraders, macrocyclic peptides, bitopics and targeted ADC payloads. 2. Biophysics: Hit follow-up and validation, routine primary SAR support using SPR (ESD to LD), MoA determination, ternary complex characterization and proximity interactions, binding kinetics insights for candidate selection and nomination, novel bitopics development, etc. 3. Compound Management & Assay Logistics: Manage compound inventory storage using cutting-edge automation and technology, facilitate primary in-vitro pharmacology by rapid generation and dissemination of assay ready plates (ARPs) Key Accomplishments: • Built a state of art biophysics laboratory with a wide array of methods & instrumentation (SPR, ITC, BLI, TSA, Mass Photometry) after joining Pfizer. This lab routinely supports ~20 small molecule drug discovery programs as well as targeted ADC, Bitopics & DAC payload discovery • Developed and implemented a robust high-throughput proximity platform for identification and progression of TPD modalities (molecular glues, PROTACs, Monovalent Degraders) • Routinely provide leadership on >20 Hit-ID campaigns per year leveraging support from CROs and working in close collaboration with partner lines like Protein Sciences, Medicinal Chemistry, External Research Solutions and Cancer Biology within Pfizer. • Provided project leadership on a high-value but difficult-to-drug target, one of the key area of my expertise. • Participated in 7 successful IND submission by authoring or reviewing in vitro pharmacology study reports.
- In this former role, served as a biophysics group leader guiding a team of PhD and non-PhD scientists (biochemists and biophysicists) - Supported more than 20 oncology small molecule programs at various stages for biophysical data needs and insights. - Specific support included pre-HTS protein and small molecule tool validation, HTS using biophysical methods (SPR & TSA), post-HTS hit follow-up and direct target engagement validation primarily using SPR, DSF, ITC and CETSA. - Gained extensive experience in DEL and ASMS screening hit follow-up (10+ campaigns each) using biophysical methods and confirming bona fide lead matter on unprecedented targets - Gained experience driving routine SAR using biophysical methods like SPR and DSF - Provided expertise in binding kinetics characterization and using binding kinetic data in late-stage optimization of lead series as well as predicting in vivo behavior of the lead candidates - Co-authored multiple IND study reports by contributing biophysical and biochemical data toward preclinical and in vitro validation of lead candidate - Gained know-how and expertise in targeting difficult-to-drug targets using biophysical methods
1. Discovered novel class of inhibitors for APS reductase enzyme using high throughput screening (HTS) and validated bacterial sulfur metabolism as a bonafide target for development of broad-spectrum antibiotics. (Developed multiple biochemical and cell-based HTS assay employing HTS platforms like AMP-Glo and Transcreener; validated and confirmed hits from 40K compound screen to identify lead compounds; performed dose-response studies to measure bactericidal activity, ITC and SPR studies to confirm direct target engagement, MOA studies to determine mode of enzyme inhibition, target ID by chemo-proteomic studies and target validation at cellular level employing conditional mutants; measured global transcriptional response of bacteria to inhibitor treatment; isolated resistant mutants for whole genome sequencing; synthesized >50 derivatives of lead compound for SAR studies). - Select Media Coverage: “Stressing out dormancy” – By Grant Miura in Nature Chemical Biology, 12, 1 (2016). “Compounds discovered with potential to treat persistent tuberculosis” – Science Daily (Nov. 17, 2015) 2. Discovered mechanism for thioredoxin-mediated regulation of activity of multiple proteins by thorough biochemical and biophysical characterization of Trx-protein interactions. (Cloned, expressed and purified multiple recombinant proteins in bulk quantities; performed site-directed mutagenesis and biochemical modification of proteins; characterized proteins using multiple biochemical and biophysical techniques including SDS-page, Western-Blot and intact mass analysis or LTQ-MS; performed ITC studies to thermodynamically characterize multiple Trx-protein interactions; developed HTS assays to probe Trx-protein interactions employing AlphaLisa and HTRF platforms) - This research has helped address a long-standing and fundamental question of how thoredoxin selects its target proteins for cellular signaling and has received wide-spread recognition.
Developed highly efficient and safe method for production of tetrazoles using continuous-flow microreaction technology. (This research has helped address a challenging problem in pharmaceutical manufacturing of tetrazoles, a bioisosteric functionality widely used in drug molecules, using continuous-flow microreaction technology. It is a benchmark discovery in the area of flow synthesis and has stimulated many subsequent investigations on safe handling of toxic and hazardous material using flow synthesis.) Media Coverage: “The Explosive Potential of Nitrogen Compounds” by Laura Howes, Chemistry World (RSC Publications)
1. Designed and developed small molecule probes for selective detection of biologically-relevant monosaccharaides like glucose for diagnostic applications. (Rationally designed, synthesized and characterized compounds for binding to monosaccharides; performed binding studies using various biophysical techniques like ITC, UV, Fluorescence, CD and 1H NMR; characterized mode of interaction and performed SAR studies to improve affinity and selectivity.) 2. Developed small molecule inhibitors of RNA to understand selectivity principles in RNA-target therapeutics. (Identified and optimized compounds inhibiting function of key RNA secondary structure; performed binding studies using SPR, ITC, fluorescence and gel-shift assays; discovered dissociation rate as a key parameter governing RNA-selectivity of small molecules.) Select Media Coverage: “Key Advance Toward Treatment For Most Common Adult Form of Muscular Dystrophy” – Science Daily (Nov. 26, 2008) “Exploring New Compounds to Target Muscular Dystrophy” – Drug Discovery & Development (Nov. 19, 2008) “Scientists discover new compounds to target muscular dystrophy” – Medical News (Nov. 19, 2008)
Major Achevements: Designed and synthesized selective PPARα agonists to improve biological activity and pharmacokinetic properties of a promising lead compound. ( Designing concise synthetic routes for target compounds; Performed multi-step synthesis of organic compounds; routinely used techniques like NMR, LC/MS, GC/MS, IR, UV, HPLC, RP-HPLC and column chromatography for purification and characterization of compounds)