Shivaprasad Venkatesha

Led a team of scientists on R&D, translational research and biomarker development. Facilitated cross-functional collaboration, strategic decision-making, scientific presentation, scientific reports, documentation, manuscript writing, patent and pre-IND applications. • Developed CAR-like receptor expressing myeloid cell platform for targeting solid tumors. • Developed AAV-based gene delivery to selectively deliver cytotoxic genes to tumor cells. • Developed iPSC-derived allogenic cell product development for the treatment of muscular degenerative diseases. • Developed AAV-based shRNA delivery to muscle to suppress DUX4 expression in Facioscapulohumeral muscular dystrophy (FSHD). • Biomarker development to assess quality and functional fitness of the iPSC-derived muscle progenitor cell (MPC) product. • Designed and executed PK/PD studies focused on safety, efficacy, dosing as well as monitoring of the immunological response to the treatment. • Established partnerships with CROs to conduct in vivo animal studies, single-cell sequencing, iPSCs generation, upscaling process development and manufacturing etc. • Single cell RNA sequencing of myogenic cells derived from iPSCs, data analysis using Loupe Browser, R, SQL, data interpretation, validation and identification of myogenic and non-myogenic biomarkers. • Planned, designed, and executed IND-enabling studies, worked with regulatory team for pre-IND document preparation and submissions. • Designed, developed, and conducted various immune assays, including multicolor flow cytometry, immunogenicity assays, and functional assays for T cells, NK cells, myeloid cells and complement activation. • Worked as Technical Lead in assay troubleshooting, assay development and qualification, SOP development, and training of scientists on flowcytometry, ligand binding platforms, cell based functional assays.

Led adoptive T cell therapy projects aimed at enhancing T cell product efficacy by maintaining immunogenicity, memory function, less exhaustion and addressing antigen escape. Advanced antigen-specific T cell expansion product derived from patients' bone marrow for autologous T cell therapy, progressing programs from preclinical development through clinical trials. Managed junior scientists, and optimized research/lab operations, contributed to product manufacturing and regulatory documents. • Evaluation of the cytotoxic activity (target cell killing), tumor recognition, cytokine release, and chemotactic markers of the T cell product. • Analysis of the T cell product including CD4:CD8 and CD45RA:CD45RO ratios, and percentages of central memory T cells, effector memory T cells, and effector T cells along with activation and exhaustion markers. • Identified biomarkers to predict treatment outcomes and the efficacy of expanded antigen specific T cells derived from bone marrow infiltrated lymphocytes in multiple myeloma and non-small cell lung cancer • Development and execution of biomarker strategies, preclinical model optimization, and clinical biomarker implementation. • Developed a novel platform for generating CAR-T cells with endogenous T cell receptor functionality using bone marrow-infiltrating lymphocytes. • Performed single cell RNA seq and ATAC seq, analysis using Loupe Brower, R, SQL and identification of differential gene expression in T cells derived from bone marrow vs PBMCs • Identified tumor antigen-specific TCR by sequencing tumor-specific T cells from bone marrow. • Established bone marrow-derived T cell isolation, expansion, and tumor antigen-specific TCR identification. • Contributed to large-scale product development and regulatory processes. • Prepared technical reports, presentations, and data analyses for internal and external stakeholders. • Developed SOPs for new assay techniques and optimized workflows to improve lab productivity

Worked on projects focused on inducing immune tolerance to autoimmune indications including multiple sclerosis (MS), anti-FVIII response to FVIII treatment in hemophilia A, and allergic reactions using engineered regulatory T cells. Trained junior scientists, collaborated with the team. • Demonstrated that FVIII-domain-expressing chimeric receptor-modified natural regulatory T cells target FVIII-specific memory B cells and suppress FVIII-specific memory B cells in hemophilia A patients. • Demonstrated proof of concept that engineered allergen-specific T-regulatory cells can provide clinical protection against severe allergic reactions in individuals already IgE sensitized to an allergen. • Assessed phenotype and function of regulatory T cells isolated from MS patients vs. healthy individuals. • Evaluated engineered Tregs expressing MBP peptide-specific TCR suppress autoimmune response to autoantigen restimulation.

Research projects 1. MicroRNA (miR) regulation of pathological events associated with autoimmune-mediated diseases • Identification of miRs and their targets that controls pathogenic Th17 and T regulatory cell balance • Identification of miRs associated with target-organ damage in autoimmune diseases • Regulation of miR expression in autoimmunity by therapeutic intervention 2. Liposome-based targeted delivery of biologics/drugs to treat target organ damage in autoimmunity • Targeted delivery of biologics or small molecule drugs to rat arthritic joints and central nervous system (CNS) of experimental autoimmune encephalomyelitis (EAE) using liposomes that display joint homing- or CNS homing peptide ligands • Evaluation of safety, efficacy and toxicity compared to systemic drug administration is under investigation 3. Identification of peptide ligands homing to the diseased CNS in MS • Identification of CNS-homing peptides in EAE using phage peptide-display library • Identification of cell surface receptor(s) of these peptides • Specificity of these peptides to human multiple sclerosis affected CNS is under evaluation 4. Immunomodulation of autoimmune arthritis by small molecule compounds/herbal formulas • Optimized dose and evaluated disease suppressive activity of small molecules and herbal formulas • Determined that these therapeutic interventions primarily regulated the genes associated with inflammatory and immune responses, including decreased antigen processing and presentation and repressed cell-mediated and antibody-mediated immune responses • Focused on understanding the modulation of T cell phenotype, functional changes in the arthritic synovium and joint damage • Identified novel mechanism of these agents in inhibiting production of pro-inflammatory inflammatory mediators, differentiation of osteoclasts, pathogenic Th17 cells and promoting induction of regulatory T cells • Microarray based gene expression studies in immune cells

Research Projects 1. Biochemical and pharmacological characterization of plant latex proteases: Role in blood coagulation and fibrinolysis • Identification, purification and characterization of novel thrombin-like and plasmin-like enzymes from plant latex • Determination of site of hydrolysis of fibrinogen molecule by these enzymes • Study the role of these enzymes in wound healing

• Taught Biochemistry, Molecular biology and Immunology to post graduate and undergraduate students under classroom and laboratory settings • Planned and executed the newer teaching material/methods, conduction of exams, evaluation of students’ progress and grading