IGB Seminar 18 October 2024 - Frank SlackFrank Slack, Ph.D., is Director of the Harvard Medical School Initiative for RNA Medicine hosted at Beth Israel Deaconess Medical Center (BIDMC). He is also the Shields Warren Mallinckrodt Professor of Pathology at Harvard Medical School. Frank Slack received his B.Sc. from the University of Cape Town in South Africa, before completing his Ph.D. in molecular biology at Tufts University School of Medicine.  He started his work on microRNAs as a postdoctoral fellow in Gary Ruvkun’s laboratory at HMS.  Dr. Slack subsequently moved to the Department of Molecular, Cellular, and Developmental Biology at Yale University, where he was a program leader in the Yale Cancer Center and the director of the Yale Center for RNA Science and Medicine.  There he discovered that microRNAs regulate key human oncogenes and have the potential to act as therapeutics.  He also demonstrated the first role for a microRNA in the aging process.  In 2014, he joined Harvard Medical School/BIDMC as the director of the Institute for RNA Medicine. In 2016 he became the Director of the HMS Initiative in RNA Medicine. In 2020 he took on the role of Director of the BIDMC Cancer Research Institute.

Dr. Slack studies the roles and uses of microRNAs and their targets in development, disease, and aging.  He has been at the forefront of the small RNA revolution.  He was part of the team that discovered the first human microRNA, let-7 and subsequently showed that it is a tumor suppressor that controls key cancer genes, such as RAS, MYC, and LIN28.  They are developing let-7 and a second microRNA, miR-34, as novel cancer therapeutics with miR-34 already in Phase I clinical trials. They also proved that microRNAs act as oncogenes and developed strategies to target these oncomiRs for cancer therapy. One of these oncomiRs, miR-155 is currently in Phase I clinical trials for lymphoma. Their research also extends to discovery of additional novel small RNAs in development, cancer, aging, and diabetes as well as identifying novel single nucleotide polymorphisms (SNPs) in the non-coding portions of the genome with an eye to identifying the next generation of targets in cancer. He is co-founder of three companies in this area, MiraDx, Impilo Tx and 28/7 Rx, and is or has been on the SAB of multiple additional companies, including Mirna Rx, miRagen Rx, Alexion Pharmaceuticals, The RNA Medicines Company.

Dr. Slack was an Ellison Medical Foundation Senior Scholar; received the 2014 Heath Memorial Award from MD Anderson Cancer Center and is an NCI Outstanding Investigator.

MicroRNAs are small non-coding RNAs that regulate gene expression to control important aspects of development and metabolism such as cell differentiation, apoptosis and lifespan. miR-21, miR-155, let-7 and miR-34 are microRNAs implicated in human cancer. Specifically, human let-7 and miR-34 are poorly expressed or deleted in different cancers such as DLBCL, and over-expression of let-7 or miR-34 in cancer cells inhibits their growth, demonstrating a role for these miRNAs as tumor suppressors in human tissue. let-7 and miR-34 regulate the expression of important oncogenes and immune checkpoint genes implicated in multiple cancers, suggesting a mechanism for their involvement in cancer. We are focused on the role of these genes in regulating proto-oncogene expression during development and cancer, and on using mimics to these miRNAs to suppress tumorigenesis. In contrast, miR-21 and miR-155 are oncomiRs and up-regulated in many cancer types. We are also developing effective strategies to target these miRNAs as a novel anti-cancer approach. Lastly, we are examining the non-coding portions of the genome for mutations and variants that are likely to impact the cancer phenotype. We have successfully resequenced the 3’UTRome and microRNAome from cancer patients, including those with a family history of cancer to identify the next generation of cancer biomarkers and targets.

In this lecture you will learn about:

Properties and functions of microRNAs

Roles for microRNAs in cancer

Methods for detecting studying and targeting microRNAs