Columbus, Ohio, United States
Summary of Qualifications · Team Leader in a start-up company overseeing from its inception and up to IND submission the drug development process for RNA therapeutics. · Expert in RNA chemistry, bioconjugation chemistry, nanotechnology, cellular and molecular pharmacology, applied to manufacturing, purification, QC, and formulation. · Managed development programs with external partners (CRO and CDMO). · Manager of a multidisciplinary team of direct reports. · Author of four patents and more than 30 scientific manuscripts in peer-reviewed high-impact factor journals. Skilled in the preparation of presentations, written reports, and regulatory filings. · Strong leadership and communication skills for working under deadlines and driving productivity.
· As a Senior Director, led end-to-end drug development activities for RNA-based therapeutics targeting various forms of cancer leading to IND submissions. · Worked with proprietary RNA nanoparticles designed to unlock the potential of RNA therapeutics in a range of cancer disease treatments. RNA nanotechnology was applied for cancer cell-specific delivery of siRNA, miRNA, and chemotherapy drugs with significantly enhanced efficacy and reduced toxicity. · Developed and implemented novel strategies for RNA nanoparticle formulation and tumor-targeting, from synthesis to nanoparticle assembly and QC. · Led activities for preclinical validation of therapeutic delivery and biological response to RNA nanoparticle-based drugs in cell culture and mouse models, including analytical characterization of the interaction between nucleic acid and the delivery agents, formulation reproducibility, stability, and transfection activity in vitro and in vivo. · Experienced in cell-based analytical assays, standard tissue culture techniques, immunofluorescence, and ELISA.
-Objective: To elucidate the molecular mechanism of RNA polymerase contacts with DNA and accessory factors that control RNA chain elongation. To study co-transcriptional folding of structured RNAs. -Accomplishments: Developed crosslinking and footprinting approaches to characterize a network of contacts between the non-template DNA, RNA polymerase gate loop, and universally conserved transcription elongation factors from the NusG/Spt5 family which enable processive RNA synthesis. Developed methods for selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) to perform cotranscriptional analysis of RNA folding. Demonstrated that a nascent RNA pseudoknot may form in the exit channel of RNA polymerase.
-Objective: Develop enhanced methods to analyze the RNA polymerase translocation ratchet. -Accomplishments: RNA polymerase uses Mg2+ to lock its translocation ratchet in register. Depletion of Mg2+ causes RNA polymerase to slide as an unrestrained thermal ratchet, and Mg2+ stiffens the ratchet. Re-addition of Mg2+ can lock RNA polymerase in a hyper-translocated register from which wild-type RNA polymerase requires 10–20 seconds to recover. The time for recovery is much longer for some RNA polymerase hinge mutants. The 778-GARKG-782 hinge on the E. coli RNA polymerase bridge helix is a key feature of the translocation ratchet. Mutations in K781 either induce backtracking (K—>A, D, Q) or hypertranslocation (K—>R, E), so K781 is a major feature of a finely tuned hinge modulating translocation. Mutations in the GARKG hinge have major effects on pausing, chemistry and fidelity. These studies provide fundamental insight into mechanisms of translocation and fidelity by multisubunit RNA polymerases. Not surprisingly, the GARKG hinge is a target of drugs
-Objective: To analyze the role of the bridge helix in RNA polymerase translocation. -Accomplishments: I generated and analyzed a large number of RNA polymerase bridge helix mutants for their effects on translocation, pausing and fidelity.