DEEPAK GURBANI

• Advanced oncology drug discovery programs by generating and interpreting high-quality structural data through protein crystallization, cryo-EM structure determination, and structure-based drug design (SBDD), directly informing compound design and candidate nomination decisions.
• Managed and maintained protein crystallization facility infrastructure; screened and optimized crystallization conditions for diffraction-quality crystals; coordinated data collection across multiple synchrotron sites (NSLS, CLS, SSRL, ANSTO-MX, ESRF, ALS) and CRO collaborations; conducted structure solution and refinement to ensure data integrity and reproducibility.
• Prepared cryo-EM grids, coordinated sample shipment to external facilities (NanoImaging Services), and processed datasets using Phenix and Chimera for global and local refinement of structural maps.
• Delivered over 30 X-ray and 28 cryo-EM structures of oncology targets bound to natural ligands and inhibitors, elucidating key molecular interactions and providing validated structural data to support project advancement and regulatory documentation.
• Applied structure- and computation-based drug design (SBDD, CADD) to evaluate binding modes, prioritize lead series, and guide hit-to-lead optimization, supporting potency and selectivity objectives for small molecule candidates.
• Collaborated on early hit-finding initiatives with internal and external discovery teams, including assay development, mass spectrometry (AS-MS), and covalent fragment library screening, ensuring data quality and traceability.
• Performed biophysical characterization (nanoDSF) to assess protein thermal stability (Tm shifts) and triage false positives, supporting mechanism-of-action studies and the advancement of tool molecules and potential molecular glues.
• Served as key personnel for laboratory safety and regulatory compliance, overseeing inspections, documentation, and adherence to institutional and federal research standards with zero violations.

• Delivered 130+ target protein–inhibitor X-ray structures, revealing key interactions and actionable design insights, documented in comprehensive reports.
• Supported structure-based drug design (SBDD) efforts across four projects in oncology, immuno-oncology, and neurological disorders, contributing to successful project progression to candidate selection.
• Designed functional surrogates for challenging proteins, enabling crystallization, structure determination, and advancement of SBDD/FBDD strategies.
• Conducted modeling studies to predict off-target interactions, leveraging cheminformatics to guide design of selective, potent molecules.
• Established a crystal-soak displacement workflow for high-throughput delivery of X-ray structures from HTS, DEL, and NMR fragment hits, facilitating rational design of selective and proprietary inhibitors by medicinal chemistry teams.
• Supported the protein sciences team by providing schematic protocols for the purification of difficult proteins, improving reproducibility and efficiency.
• Successfully mentored team members on crystallization strategies, achieving superior diffraction results and knowledge transfer across the team.

• Executed cloning, expression, purification, and X-ray structure determination of JNK2 kinase–inhibitor complexes (PDB: 7N8T, 8ELC).
• Mentored junior staff in gene cloning, protein purification, crystallization, and structure determination, fostering skill development and team capability.
• Authored intramural and extramural grant proposals, successfully contributing to laboratory funding and resource acquisition.

• Solved crystal structures of human KRAS GTPase bound to GDP, SML-8-73-1 inhibitor, and mutant forms [PDB IDs: 4LDJ, 4NMM, 4OBE, 4WA7, 4TQ9, 4QL3], providing insights into inhibitor binding and conformational dynamics.
• Conducted cloning, expression, purification, and characterization of TAK1 kinase inhibitors, including reversible (NG25, Takinib) and irreversible covalent compounds (SM1-71), using biophysical, biochemical, and cellular assays; pioneered meta-substituted pyrrolopyrimidine covalent TAK1 inhibitors [PDB IDs: 5V5N, 4O91, 5J9L, 5J8I, 5J7S, 5JH6, 5E7R, 5JK3].
• Designed and validated a selective irreversible Src kinase inhibitor (DGY-06-116), with structural validation [PDB IDs: 6ATE, 6E6E] and patent protection (U.S. Patent Application WO-2020257385-A1).
• Solved Glutathione S-transferase structure [PDB ID: 5J41], contributing to functional and structural insights for enzymatic studies.

• Analyzed polycyclic aromatic hydrocarbons (PAHs) in urban ambient air, coal tar combustion emissions, and diesel exhaust particles, assessing their genotoxic potential in human lung cells (A549 and BEAS-2B).
• Purified the ATPase domain of human topoisomerase-IIα and conducted biochemical inhibition studies with environmentally relevant quinone pollutants; quantified quinone-stabilized topoisomerase-IIα–DNA complexes using agarose-trapped DNA assays.
• Measured γ-H2AX levels in human lung cells as a marker of DNA double-strand breaks induced by quinone-mediated topoisomerase-IIα inhibition, linking environmental pollutants to cellular genotoxicity.