Rachel Litman Flynn, Ph.D.
Associate Professor of Pharmacology, Physiology & Biophysics and Medicine
Section of Hematology and Medical Oncology
Research Interests
The focus of the Laboratory of Genomic Instability and Cancer Therapeutics is to understand the mechanisms regulating mammalian telomere maintenance and to understand how defects in this process contribute to premature aging and cancer progression. The hope is that these studies will allow us to gain the mechanistic insight necessary to define novel targets and/or strategies in the treatment of human disease.
In my lab we use a combination of biochemical and cell biological approaches to study the function of mammalian telomeres. Telomeres cap the ends of linear chromosomes and provide a molecular barrier for the human genome. Following each cell division, progressive telomere shortening erodes that barrier and compromises the stability of the genome. Critically short, or dysfunctional telomeres induce replicative senescence and/or cell death and ultimately, lead to cellular aging. Cancer cells, however, overcome the replicative senescence associated with critically short telomeres by exploiting mechanisms of telomere elongation. Reactivation of the enzyme telomerase or activation of the Alternative Lengthening of Telomeres (ALT) pathway accounts for cellular immortalization in the majority of all human cancers. Clinical trials are currently underway to test the efficacy of telomerase inhibitors in the treatment of telomerase-positive cancers; however, there are no known treatments for ALT-positive cancers. By gaining a better mechanistic understanding of how normal telomeres are maintained, and how dysfunctional telomeres bypass replicative senescence, we hope to identify novel therapeutic approaches in the treatment of both premature aging syndromes and cancer.