I am currently a Director, Investigative Toxicology, at Alnylam Pharmaceuticals where I am leading mechanistic efforts related to nonclinical safety evaluation of RNAi therapeutics targeting a variety of tissues, including the liver, eye, and CNS. I earned a Bachelor of Arts in Chemistry and Biochemistry from the University of Colorado in 2007, and a PhD in Biological and Biomedical Sciences from Harvard University in 2012, working with Dr. Carl D. Novina on novel regulators of microRNA biogenesis and function. After completing a postdoctoral fellowship in the RNAi Therapeutics group at Novartis Institutes for BioMedical Research, I joined Alnylam Pharmaceuticals in 2014, and assumed positions of increasing responsibility in the Early Development organization. In addition to leading the investigative toxicology function, I co-led cross-functional CNS platform efforts to optimize and de-risk novel conjugates for CNS diseases, enabling the advancement of our first CNS program to the clinic. More recently, I have been co-leading the RNA Sciences platform team tasked with optimizing siRNA designs for RNAi and beyond. I have successfully passed the exam to become a Diplomate of the American Board of Toxicology (DABT) in 2016 and was awarded the OTS Young Investigator Award in 2020.
One of my most notable contributions to the RNAi therapeutics field includes demonstrating for the first time that the main driver of GalNAc-siRNA hepatotoxicity in vivo is seed-based off-target activity and that thermally-destabilizing seed modifications can mitigate this liability (Nat Commun. 2018). This discovery fundamentally changed our siRNA lead selection paradigm and provided the framework for the ESC+ platform, with multiple programs now in the clinic. In addition, I have been leading the efforts to establish and implement a de-risking paradigm for unnatural monomers utilized in our RNAi therapeutics, including publishing the first comprehensive in vitro and in vivo de-risking of 2′-fluoro nucleotides (Nucleic Acids Res. 2019; March 2019 OTS Paper of the Month). Using this de-risking paradigm, we have been able to transition multiple other unnatural nucleotides to development to support platform advances.
- American Board of Toxicology (ABT)
- Oligonucleotide Safety Working Group (OSWG)