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Joseph Costello

Dr. Joseph F. Costello is a Professor in the Department of Neurological Surgery at University of California, San Francisco (UCSF) and Karen Osney Brownstein Endowed Chair in Molecular Neuro-Oncology, UCSF. He studied Biology at Marquette University and obtained his Ph.D. in Neuroscience from Loyola University. From 2008-2014, he served as Director of the UCSF based NIH Roadmap Epigenome Mapping Center.  He currently serves as Director of the NIH Training Grant on Translational Research in Brain Tumors at UCSF.

Airc Lecture - Precision medicine: How to exploit the growing knowledge on the evolving genomes of cells to improve cancer prevention and therapy

Research is showing that the biological characteristics of our cells and tissues can be influenced by early environmental exposures. Such “memories”, including behavioral, dietary, hormonal, and chemical, may be maintained over a lifetime, or even across generations, as marks on our genomes. Although such marks do not modify our DNA’ sequence, and are therefore called “epigenetic”, they do modify its accessibility and use. This is why many epigenetic signatures on the DNA have profound implications for human health and disease susceptibility. It is also the reason for the international blossoming of epigenetics research, and of the growing public awareness. 
The good news about epigenetic programs is that they are experimentally reversible and even reprogrammable in the cells. Thus, therapeutic epigenetic approaches are a potential new avenue in cancer therapy and regenerative medicine. However, a basic understanding of complete human epigenomes has been lacking so far. Creating catalogues of reference epigenomes of all human cell types and tissues holds promise for many facets of human health, including the prevention and cure of cancer.
One early success and milestone has been the “NIH Epigenome Roadmap Initiative”, which recognized and enthusiastically supported the immense potential of such an endeavor. The effort to create a full catalogue of human epigenomes in health and disease has now advanced to an international level, united by the International Human Epigenome Consortium (IHEC).
The genome and epigenome of cancer cells evolve as the tumor grows, particularly under the selective pressure of anti-cancer therapy, with a dynamic which reminds in some way the epigenome’s modifications that happen during the embryonic development. Precision medicine in oncology uses the specific characteristics of a patient’s normal and tumor genome and epigenome to select an appropriate therapy for such patient.  If the evolving nature of the tumor complicates this therapeutic approach, it also provides new opportunities to delay or prevent tumor recurrence when the evolutionary path is predictable.
Knowing more about how tumors form and evolve, and how old and new personalized therapies may be better used in such a context, is helping to achieve unprecedented success and to improve overall survival in cancer patients.  Although there is much room for improvement, there is also cause for optimism in the personalized medicine approach to treatment for cancer patients.


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