• Lead the functional studies group in a $50M Broad-IBM Research collaboration with teams across Broad Institute, involved in collaborative and independent investigation of drug response and resistance in cancer.• Directly supervise a group of experimental and computational scientists creating a systematic Cancer Resistance Map in several cancer disease areas, characterizing resistance mechanisms and uncovering novel vulnerabilities of resistant cancers.• In-depth computational genomic analysis and experimental follow-up on novel drivers of cancer and drug resistance in ovarian, breast, high-mutational burden cancers, pan-cancer cohorts.• With Termeer Center for Targeted Therapies at MGH, characterized novel pathways of cancer progression and resistance to treatment in a HR+/HER2- patient cohort with CDK4/6/ERa-targeted treatment, in particular, resistance mechanisms that target epigenetic drivers. WES/RNA-Seq/scRNA-Seq/spatial analysis of patient samples.• Therapeutic discovery and demonstrated expertise in cancer biology, genetics, immuno-oncology, oncogenic signaling pathways, and target ID and validation. Identified novel vulnerabilities in drug-resistant cancers using functional genomics approaches, including whole-genome CRISPR screening, as well as by compound screens and combination treatment design.• Single-cell assays such as single-cell RNA-Seq and mutation identification in single-cell data for tumor subclones. Identified unique cell populations in tumor therapeutic response and resistance by single-cell RNA sequencing of patient tumor samples pre- and post-treatment, followed by detailed experimental interrogation in cell lines and organoids. Co-PI/co-I on funding applications and successfully funded projects.

• Established and led a high-performance team of experimental and computational scientists. Built the experimental capacity of the Cancer Genome Analysis Group and integrated it with computational genomics part of the lab.• Successfully obtained DOD and NIH funding as co-Investigator.• Performed whole-exome, RNA-Seq, and single-cell analysis of patient cohorts and experimental interrogation of drug-resistant pathways. Cloud compute for genomic analysis: GCP, AWS, Terra.• Spearheaded single-cell analyses including scRNA-Seq/snRNA-Seq, CITE-Seq, CyCIF to interrogate drug-resistant populations in ovarian cancer patient samples (HGSOC) in neoadjuvant chemotherapy setting. • Discovered a novel chemoresistant cell population in ovarian cancer through patient genomic analysis and experimental validation, in collaboration with clinical research team at DFCI (Dr. Matulonis); AACR 2023 talk.• Validated the chemoresistant pathways in cell line models and proposed novel mechanisms of persister cell targeting.

• Led an early discovery project within Broad-Bayer Collaboration in Oncology portfolio.• Analyzed predictive protein folding models (AlphaFold) and mutational enrichment in protein structures and protein-protein interfaces.• Discovered a new class of cancer driver genes and mutations that target RNA biology and deregulate RNA deadenylation and translation, in particular n melanoma and high-mutational load cancers.• Led in-depth experimental validation, in vitro and xenograft studies, MOA, in-depth pathway analysis, RNA stability and active translation (polysome) profiling and sequencing.• BroadNext10 Broad Institute Award - Principal Investigator “New multiplexed methods for rapid protein-protein interaction and compound screening”.

• Project # 1: Analyzed patient, cell line data (genomic, CRISPR screening, metabolomic, protein structure, druggability); the insights played a major role in Series A raise for this Company.• Project # 2: Analyzed mutational data in cancer to probe the role of a certain protein class and assess them as drug targets for a go/no-go decision.• Project # 3: Analyzed gene fusion data from a multi-omic (RNA-Seq, Whole-Genome Sequencing WGS) dataset to guide target selection in multiple cancer settings; coordinated the Company team with Boston-available resources for in-depth data analysis and decision-making in the pre-Series A round.• Provided in-depth analysis for scientific decision-making, target ID and prioritization, proof-of-concept approaches for initial investment, seed-stage, Series A, and established companies. Covered areas of cancer genomic analysis, single-cell RNA Sequencing and other ‘omics datasets, target ID, target prioritization, biomarker discovery, druggability assessment, novel therapeutic strategies.• Advised and directly contributed key results that led to company formations, successful raise of Series A funding, meeting key deliverables/milestones.

• Developed and ran high-throughput screen of protein-protein interactions in this pathway (>140,000 compounds), characterized hits and SAR compounds in vitro and in primary macrophages, developed a mouse model for a protective CARD9 variant. These first-in-class immunomodulatory therapeutic prototypes are in continued development with a leading industry partner.• Biochemical, biophysical and cell-based high-throughput assays: developed, optimized, and deployed in screening mode.

• Therapeutically targeted protein-protein interactions of cell death pathways in cancer and discovered distinct mechanisms of pro-death BCL-2 proteins (BAX and BAK) activation. • Achieved specific targeting of previously undruggable oncogenic KRAS by developing staple peptides that directly engage and inhibit its activity.

• Developed RNAi delivery agents for therapeutic applications: synthesized and characterized a diverse library of >1000 lipidoid compounds for RNAi delivery, assessed their specific cell-based activity and developed nanoparticle lipidoid formulations for in vivo RNAi delivery into liver, lung, or peritoneal macrophages. Multiple publications and patents.• Lipidoid biomaterial formulations were licensed to several companies, including a leading gene therapy company.