Charlotte J.

Expanded leadership scope from previous role, spanning DC nomination, IND-enabling studies, Phase 1 translational strategy, regulatory document authoring, and cross-functional collaboration. Serve as Pharmacology Lead overseeing Lead Optimization and DC nomination of a bispecific antibody for inflammatory diseases.  Coordinate across the screening cascade to iterate binder and linker optimization to generate a candidate engineered to improve patient response to treatment. Accelerate DC timeline compared to internal base-case goal. Act as Study Director/Scientist on seven nonclinical primary pharmacology reports submitted in IND Module 4 (four conducted internally, three directed at CRO). Reports were of such high quality that Regulatory accelerated Module 4 finalization by one month due to minimal needed revisions.  Architect translational strategy for an active Phase 1 trial of a bispecific antibody, spanning assay development, CRO transfer, data delivery timelines, and synthesis of orthogonal target engagement and two pharmacodynamic readouts to support Phase 2 decision making. Design, develop, transfer, and validate translational assays in three months.  Develop technically challenging in vitro assays in primary human cells and tissue to assess MoA, identify biomarkers, and evaluate indication expansion, in collaboration with Precision Genetics. Design four in vitro potency assays to support human PK modeling for dose selection in Phase 1.  Direct murine in vivo efficacy (CIA, DSS, TNBS) and PK models at CRO partners to evaluate PK, PD, and efficacy of novel combinations and lead molecules. Directly supervise a research intern.

Biology Lead for three bi/trispecific T cell engager programs targeting immuno-oncology indications (two internal, one in collaboration with a large pharmaceutical partner). Directly supervised an experienced Research Associate. Defined screening strategy and mechanism of action investigations for multi-specific T cell engagers across Target Validation, Lead Identification, and Lead Optimization; supported Go/No-Go decision-making for DC nomination. Partnered directly with Protein Engineering to define optimal epitope, affinity, and valency combinations and assess Fc modification impact on in vivo PK/PD, informing candidate selection across three programs. Developed in vitro target engagement and complex in vitro co-culture assays to assess on- and off-target T cell activation and cytotoxicity, informing SAR of geometries, binders, and linkers. Designed and executed in vivo murine IO xenograft models; analyzed primary tissue to assess PK, PD, biodistribution, serum stability, and CRS risk.

Immunology lead for two immuno-oncology programs. Manage project-specific Biology Sub-team Meeting Series to prioritize project goals and timelines. Defined targeting strategy and mechanism of action of small molecule inhibitors for immuno-oncology targets at multiple stages in the pre-clinical pipeline. Processed and analyzed primary tissue from in vivo models to assess T, NK, and myeloid cell frequency, localization, and phenotype using flow cytometry to evaluate efficacy and pharmacodynamics (12 color). Developed target engagement assays to assess primary T and NK cell activation in proximal- and distal-to target readouts (cytokine quantification, intracellular and phospho-flow, qPCR). Developed complex in vitro co-culture models to assess T cell cytotoxicity in human and murine systems. Collaborated in interdisciplinary teams (chemistry, pharmacology, DMPK) to execute in vivo/ex vivo studies. Presented findings and recommendations at technical research and high-level strategy meetings.

Studied primary patient samples to identify immune cell receptors involved in recognition of nonclassical MHC class I-like antigen presenting molecules. Established workflow process for robust in vitro expansion of primary antigen-specific T cell clones. Supervised three graduate students and one undergraduate student. Assessed T cell response to non-classical MHC Class I molecules to establish novel role of MHC-Ib molecules in the immune response to tumor cells. Designed flow cytometry and single-cell PCR-based sequencing panels to evaluate NK and T cell receptor diversity on immune cells to evaluate potential targets for novel immunotherapies.

Implemented computational immunology methods to profile donor-unrestricted T cells that are modulated in a Phase I trial assessing safety and immunogenicity of BCG revaccination in an adult cohort. I used multi-parameter flow cytometry and immunosequencing to define populations that undergo expansion after BCG vaccination, and revealed novel populations that may be contributing to protective immunity to tuberculosis in a vaccine setting.

Implemented in vitro and computational immunology methods to profile donor-unrestricted T cells in primary patient samples enrolled in intervention and vaccination clinical trials. Directly supervised five graduate students, three undergraduate students, and three high school students. Assessed donor-unrestricted T cell activation and function using CD1 and MR1 tetramers to profile novel T cell populations that can be modulated by novel vaccination strategies. Generated and analyzed multi-parameter flow cytometry (16 color) and single-cell sequencing data to establish predictions for the effect of novel vaccination strategies on T cell subsets (R-Fluent, experience implementing t-SNE, UMAP, TCRdist, GLIPH, OpenCyto, Seurat). Engineered primary T cells with recombinant T cell receptors using a lentiviral system. Presented (oral and poster) at five international meetings and to external collaborators and funders. Applied for and received funding for two individual training awards (NIH T32, NIH TL1).

Independently instructed a section of Introduction to Microbiology (MICRO 302).

Independently investigated the regulation of proteins involved in crossover formation during meiosis.

I worked with students to develop study plans designed to raise exam scores and information retention, as well as improve confidence and mastery of course material. Classes tutored include: general biology, chemistry, physics, organic chemistry, and calculus

Collaborated with staff epidemiologist to construct an epidemiological profile of dynamic HIV/AIDS trends in San Luis Obispo county using data from 1999-2012.

Relevant Coursework: Vaccine Epidemiology, Innate Immunity and Immunopathology, Biochemistry and Genetics of Pathogens, Introduction to Statistical Computing, Summer School for Computational Genomics (Mount Sinai School of Medicine).

summa cum laude Outstanding Biological Sciences Graduate Award Recipient, 2015 Drew Theil Memorial Scholarship Recipient, 2014. Relevant Coursework: General Virology, Microbiology, Vertebrate and Human Anatomy and Physiology, Applied Experimental Design and Regression Analysis, Statistics, Biochemistry and Biotechnology.