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Phillip D. Zamore Bio:

Phillip D. Zamore, Ph.D. has been an Investigator of the Howard Hughes Medical Institute since 2008. In 2016, he became the Chair of the RNA Therapeutics Institute, which was established at the University of Massachusetts Medical School in 2009. Dr. Zamore also is Professor of Biochemistry and Molecular Pharmacology, the department he joined in 1999, and he became the Gretchen Stone Cook Professor of Biomedical Sciences in 2005.

Dr. Zamore received his A.B. (1986) and Ph.D. (1992) degrees in Biochemistry and Molecular Biology from Harvard University. He then pursued postdoctoral studies on the role of the RNA binding proteins in Drosophila development at The Whitehead Institute for Biomedical Research, in Cambridge, Massachusetts.

Dr. Zamore’s laboratory studies small RNA silencing pathways in eukaryotes and prokaryotes, including RNA interference (RNAi), microRNA, and PIWI-interacting RNA pathways. Dr. Zamore and his collaborators seek to use these insights to design therapies for human diseases, including Huntington’s disease. Under Dr. Zamore’s mentorship, the Zamore Lab has produced dozens of researchers working at top institutions both in the United States and abroad.

In 2015, Dr. Zamore was awarded the Chancellor’s Medal for Excellence in Scholarship at the University of Massachusetts Medical School. To date, Dr. Zamore has more than 150 publications and has been among the most highly cited researchers for more than a decade. He serves on the editorial boards of numerous journals and is in demand as a presenter at conferences and institutions worldwide.

Dr. Zamore holds more than 20 patents, with other applications pending; he was elected a Fellow of the National Academy of Inventors in 2014. In 2002, Dr. Zamore co-founded Alnylam Pharmaceuticals (Cambridge, MA), a publicly traded biotech company which now has more than 1000 employees and multiple drugs in clinical trials. Alnylam’s first drug, ONPATTRO, a first-of-its-kind RNAi therapeutic, for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults, was approved by the FDA in 2018. In 2014, he co-founded Voyager Therapeutics in Cambridge, MA.

Chair and Professor at University of Massachusetts Medical School, Phillip Zamore, joins the show to discuss a new method of gene silencing called RNA interference (RNAi).

Tune in to learn the following:

  • How the RNAi system is analogous to the basis of vaccination
  • How specifically the method of RNAi prevents a protein from being made and what happens to the mRNA after it has been cut
  • Why RNAi will never replace the knock-out method, and the benefit of combining both methods

Zamore states that the world’s diseases can be divided into two broad categories: those with mutations in the genome that can be addressed by turning off the gene forever, and those with mutations in the genome that can be addressed by lowering the amount of a gene product, as opposed to turning off the gene completely.

The gene knock-out method is used for the first kind of disease, and the effects of the knock-out are irreversible. This makes the method a good tool for studying model organisms in the lab, but rather risky as a therapeutic intervention for humans. This is where a new method called RNA interference comes into play and holds promise for the future of medicine and the treatment of diseases.

RNA interference is a way of destroying messenger RNA (mRNA) in order to prevent the creation of a protein. Unlike other methods, RNA interference uses a natural cellular pathway, which makes it more effective than other mechanisms in turning off disease genes. And just like taking a drug, stopping this process means stopping any unwanted side effects, which means it’s a lot safer and less risky than the knock-out method.

There are currently two RNAi drugs on the market, both of which direct small RNA (sRNA) to the liver where the protein in question is made. By way of preventing the creation of that protein, the disease gene is turned down (almost off). Zamore explains why the liver is particularly amenable to these drugs, and the ongoing research and development taking place for drugs that target proteins made in other areas of the body.

He also discusses the near-term goal of bringing to market an sRNA drug that blocks the production of a protein in the cholesterol biosynthesis pathway. This drug would function as a replacement for statins, and comes with fewer side effects and would only need to be taken by a patient twice per year.

Zamore brings an impressive amount of insight and information to the show, discussing a number of topics in depth but with enough clarity to follow along with ease.

Learn more by visting his Google Scholar page at https://scholar.google.com/citations?user=xYLmV7YAAAAJ&hl=en.

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