RAKESH DESHAR

Targeted Protein Degradation & RNA Modulation

Degrader Platform Development & HTS Execution:

• Established high-throughput 1536-well cell-based screening platform for molecular glue discovery targeting undruggable proteins, achieving robust assay performance (Z' >0.5) and enabling screening of 300K+ compound libraries across multiple degrader programs
• Successfully executed large-scale HTS campaigns for molecular glue and RNA modulator discovery, performing cascade of hit confirmations, orthogonal assays, and lead profiling to advance hit-to-lead optimization
• Developed and implemented HiBiT-based CETSA (Cellular Thermal Shift Assay) platform to identify novel target binders and validate engagement for degrader programs, supporting mechanism-of-action characterization
• Adapted and miniaturized advanced cell culture systems for automated, 1536-well HTS applications, maintaining assay robustness, sensitivity, and data quality across diverse targets
• HTS SAR & Hit Validation:
• Supported weekly HTS SAR activities in close collaboration with medicinal chemistry teams, delivering rapid turnaround profiling data that successfully led to discovery of potent inhibitors and degraders
• Designed and executed cascade assays (confirmatory screens, dose-response profiling, counter-screens) to validate hits, generate high-quality SAR, and prioritize leads for advancement
• Automation, Data Integration & Cross-Functional Collaboration:
• Partnered with automation engineers to troubleshoot robotic liquid handling systems and optimize workflows on integrated platforms, ensuring seamless HTS execution and >95% system uptime
• Collaborated with data scientists to develop HTS plate layouts, data capture pipelines, and analysis tools (TIBCO Spotfire) for efficient data visualization, QC, and sharing across project teams
• Maintained rigorous documentation standards in ELN (Electronic Laboratory Notebooks) and ROPs (Record of Operating Procedures) to ensure reproducibility and compliance

Targeted Protein Degradation Discovery Platform

Biochemical & Cellular Assay Development:

• Developed and validated biochemical and cell-based assays (TR-FRET, AlphaLISA, NanoBRET, NanoBiT, HiBiT degradation, HaloProtac3) to identify, characterize, and profile protein degraders across multiple therapeutic programs
• Established PPI discovery platforms using TR-FRET and AlphaLISA to measure ternary complex formation, target engagement, and cell permeability of PROTACs and molecular glues
• Conducted E3 ligase deconvolution studies using BioID proximity labeling and co-immunoprecipitation coupled with mass spectrometry to identify natural E3 ligases for novel protein targets
• Cell Line Engineering & Assay Platforms:
• Generated HiBiT- and Halo-tagged endogenous cell lines using CRISPR/Cas9 gene editing and exogenous stable cell lines via lentiviral transduction and Flip-In systems to support degrader screening and profiling platforms
• Established cell-based and cell-free assays for characterization of degrader potency, selectivity, mechanism of action, and pharmacology
• HTS & Cross-Functional Collaboration:
• Executed high-throughput drug screening campaigns using Mosquito LV liquid handler to identify novel protein degraders, delivering hits for downstream validation and SAR development
• Worked closely with chemistry, protein purification, and biology teams to drive hit-to-lead transitions, providing critical assay support and data interpretation throughout drug discovery campaigns
• Employed IncuCyte live-cell imaging systems for real-time monitoring of degradation kinetics, cell viability, and functional readouts
• Conducted literature searches to identify and propose new degrader targets aligned with therapeutic priorities

Cancer Biology & DNA Repair Mechanisms

• Expressed, purified, and characterized recombinant proteins from bacterial systems to identify and validate nuclease activity of candidate DNA repair enzymes
• Identified and characterized a novel DNA repair protein required for homologous recombination-mediated double-strand break repair, contributing to fundamental understanding of genome stability mechanisms
• Designed and executed experiments investigating molecular mechanisms of cancer genetics and epigenetics, including HR/NHEJ DNA repair assays, laser micro-irradiation, flow cytometry, and live-cell imaging
• Established stable cell lines using lentiviral transduction to screen for novel RNA-associated heterochromatin-binding proteins and epigenetic regulators
• Authored 3 peer-reviewed publications in top-tier journals (Nucleic Acids Research, FEBS Journal, Biochemical and Biophysical Research Communications) advancing understanding of cancer biology and DNA damage signaling
• Secured NIH/NCI T32 Fellowship in Oncology Translational Research
• Mentored graduate students in cell biology and molecular biology techniques; successfully trained multiple trainees in experimental design, data analysis, and manuscript preparation