Jacqueline Salotti

• Serve as Biology Program Team Lead (PTL) for the Huntington’s disease program developing small-molecule splicing modulators targeting HTT and PMS1 (DNA mismatch repair pathways). • Lead cross-functional efforts across Medicinal Chemistry, DMPK, Toxicology, Bioinformatics, and AI/ML teams to advance programs from discovery through drug candidate selection and IND-enabling activities. • Drive translational and regulatory strategies by integrating efficacy, PK/PD, biomarker, and safety data to support go/no-go decisions and portfolio progression. • Integrate transcriptomic (RNA-seq) and quantitative proteomic datasets to evaluate target engagement, selectivity, mechanism of action, and translational biomarkers supporting preclinical and regulatory decision-making. • Contribute to non-GLP toxicology, tolerability, and safety assessment studies across multiple species to support candidate progression and IND-enabling activities. • Contribute to preparation of briefing documents supporting FDA interactions and regulatory strategy. • Manage CROs, external collaborations, and direct reports to support execution of in vitro and in vivo pharmacology studies. • Contribute to grant applications, intellectual property development and patent filings.

• Lead early drug discovery efforts including HTS development, translational screening platforms, SAR biology, and target discovery across neurodegeneration and oncology programs, and served as Program Team Lead (PTL) for DNA mismatch repair gene-targeting programs. • Leverage reverse-translational biology, human genetics (GWAS), and patient-derived molecular and clinical datasets to identify therapeutic targets, define disease mechanisms, and guide biomarker and drug discovery strategies. • Develop and implement cell-based assays, including RT-qPCR, MSD, CellTiter-Glo (CTG), immunofluorescence-based neuronal characterization and quality control, luciferase reporter and minigene splicing assays, and CAG repeat expansion assays in cell lines and patient-derived iPSC-derived neuronal cultures to support target validation, mechanism-of-action studies, pharmacology, and translational biomarker development. • Develop and utilize CDX, transgenic, and humanized mouse models to evaluate drug efficacy, target engagement, and PK/PD relationships. • Establish and manage collaborations with CROs and academic partners to support screening, assay development, and preclinical studies. • Implement data management and workflow systems, including Benchling and CDD Vault, to support compound tracking and cross-functional data integration.

• Led translational oncology and aging research programs focused on oncogenic RAS signaling, oncogene-induced senescence (OIS), and RNA-mediated mechanisms regulating tumor progression and inflammation. • Identified mechanisms by which C/EBPβ and its mRNA localization regulate senescence bypass and SASP-associated phenotypes. • Defined signaling pathways downstream of oncogenic RAS controlling senescence, tumor progression, and inflammatory responses. • Developed molecular and cellular approaches to study RNA regulation, including RNA-IP, CLIP, protein co-IP, RNA FISH/immunofluorescence multiplexing, and translational regulation assays. • Applied confocal and super-resolution microscopy (Airyscan, ELYRA) to investigate RNA localization, protein dynamics, and signaling mechanisms. • Designed and executed cellular, molecular, and in vivo studies, including syngeneic and genetically engineered mouse models (GEMMs), to evaluate target biology and oncogenic signaling. • Developed mechanistic, imaging-based, and cell-based assays to investigate senescence pathways and therapeutic hypotheses. • Performed functional genomics studies using RNAi, shRNA, and CRISPR approaches coupled with transcriptomic profiling to identify pathway dependencies and mechanisms of oncogene-driven phenotypes. • Collaborated with the NCI Gene Targeting Facility to develop CRISPR-engineered and genetically engineered animal models for in vivo target validation. • Coordinated studies integrating transcriptomics, proteomics, functional genomics, and imaging to generate mechanistic and translational insights. • Mentored graduate students and postdoctoral fellows; published in peer-reviewed journals and presented at international scientific conferences.

• Supported onboarding and orientation of new postdoctoral fellows and post-baccalaureate trainees to NIH research programs, policies, and career development resources. • Contributed to planning and execution of the NCI Postdoctoral Retreat, including speaker coordination, session moderation, and evaluation of scientific poster and oral presentations. • Helped organize networking and community-building events to foster collaboration and engagement across the NIH trainee community.

• Led independent research investigating the antitumor mechanisms of FGF2 in oncogenic RAS-driven cancer models. • Designed and optimized cellular pharmacology studies evaluating FGF2 signaling, FGFR/SRC pathway modulation, and downstream effects on cell viability, growth arrest, and senescence-associated phenotypes. • Investigated the contribution of oncogenic RAS signaling pathways, including MAPK, PI3K/AKT, SRC, and related signaling networks, to tumor cell proliferation and stress responses. • Evaluated small-molecule inhibitors targeting FGFR and downstream signaling pathways to characterize pharmacologic modulation of RAS-driven tumor phenotypes. • Applied molecular, cellular, and phenotypic assays to characterize signaling mechanisms and therapeutic responses in RAS-driven tumor cells.

• Supervised large-scale manufacturing operations for solid oral dosage forms, leading and training a team of 100+ production operators in a GMP-regulated pharmaceutical environment. • Developed and implemented Standard Operating Procedures (SOPs) to support manufacturing consistency, operational efficiency, and regulatory compliance. • Led deviation and customer complaint investigations, performing root cause analyses and implementing corrective and preventive actions (CAPA). • Conducted process optimization and operational efficiency initiatives to improve productivity, workflow performance, and manufacturing reliability.

• Prepared, reviewed, and submitted regulatory documentation supporting registration of diagnostic reagents and medical devices with the Brazilian Federal Health Surveillance Agency (ANVISA). • Supported regulatory compliance activities by ensuring products and documentation met applicable regulatory requirements and quality standards. • Gained early experience with regulatory submissions, documentation management, and interactions within a regulated healthcare environment.