Professor Niall Howlett, University of Rhode Island, USA.
Fanconi Anemia and the Maintenance of Genome Stability.
Genome instability is a pervasive feature of cancer. Understanding the origins of genome instability and the cellular processes that safeguard the genome is paramount to devising improved diagnostic and therapeutic approaches to cancer and other diseases. One cellular pathway that plays a critical role in the maintenance of genome stability is the Fanconi anemia pathway. Fanconi anemia (FA) is a rare genetic disease characterized by congenital abnormalities, increased risk for bone marrow failure and cancer, and premature mortality. Therapeutic options for FA patients are extremely limited and the median life expectancy is 29 years. FA is caused by mutation in 22 genes, the protein products of which function cooperatively in the FA pathway to maintain genome stability. A key step in the activation of the FA pathway is the monoubiquitination of the FANCD2 and FANCI proteins, which promotes their assembly into discrete nuclear foci. Importantly, the domain structure, regulation, and function of FANCD2 and FANCI remain poorly understood.
In this talk, the clinical features of FA, what is known of the underlying biochemistry of FA, and how the study of this rare disease has far reaching beneficial implications for medicine in general will be described. Finally, recent unpublished findings from the Howlett laboratory describing a novel mechanism by which the FANCD2 protein reads and binds to chromatin will be presented.
About the Presenter
Niall G. Howlett is an Associate Professor in the Department of Cell and Molecular Biology at the University of Rhode Island and Program Coordinator for the NIH-funded RI-INBRE program. He received a B.Sc. in Industrial Biochemistry from the University of Limerick and a Ph.D. in Biological and Molecular Biosciences from Oxford Brookes University. He performed postdoctoral research at Harvard School of Public Health, the Dana-Farber Cancer Institute/Harvard Medical School, and the University of Michigan. His research program is focused on the eukaryotic DNA damage response and the etiology of hereditary cancer susceptibility syndromes associated with defective DNA repair, with a particular focus on the molecular pathogenesis of Fanconi anemia (FA). He has made numerous important contributions to the field of FA research culminating in several high impact publications, including publications in Science, Molecular Cell, and Blood. Over the course of his independent faculty position at the University of Rhode Island he has mentored over 30 trainees including postdoctoral research fellows, graduate students, and undergraduate students. The Howlett laboratory has received funding from multiple federal and private sources including the National Institutes of Health, the Department of Defense, the Leukemia Research Foundation, and the Fanconi Anemia Research Fund.
Tea/coffee will be available at 11h45.