Epigenetics
deacetylase (HDAC) inhibitors, Zolinza (vorinostat) and Istodax (romidepsin), are FDA-approved for the treatment of cutaneous T-cell lymphoma (CTCL). In addition, valproic acid, an HDAC inhibitor, is wide- ly used to treat epilepsy and bipolar disorder, and is also being used for the treatment of migraine headaches and schizophrenia.
The principle of epigenetic therapy is to reverse pathological gene expression changes. There have been concerns that epigenetic therapy could adversely affect normal cells through reactivating, for example, imprinted genes, or even leading to the development of cancer. To date, these concerns have not been substantiated in vivo. Novel epigenetic targets such as histone methy- lases and demethylases, histone acetylases, and readers (bromodomains and chromodomains) are currently the focus of drug discovery and develop- ment efforts. It is expected that more than six addi- tional epigenetic drugs and a number of new diag- nostic tests for cancer based on epigenetic biomark- ers will receive FDA approval over the next decade.
Conclusion
Although our understanding of epigenetics remains in its infancy, the rapid development of new tools and technologies to define genome-wide epigenetic variations in humans will soon put this field on the same trajectory as genomics following improve- ments made in DNA sequencing technologies. The potential for effective new epigenetic therapies and diagnostic tests for a wide range of diseases beyond cancer is holding great promise.
DDW
Dr John Rosenfeld has held a scientific position in research and development at EMD-Millipore since 2003. Currently, he manages chromatin biology product development, innovating gene regulation research tools for life scientists, in particular kits and reagents for ChIP and RNA-binding protein immunoprecipitation (RIP). Dr Rosenfeld per- formed postdoctoral studies with Dr Ronald Evans of the Salk Institute of Biological Studies, and obtained his PhD in molecular biology and bio- chemistry from the University of California Irvine, in the laboratory of Dr Timothy Osborne. Dr Rosenfeld’s scientific career and publication record has focused on transcription in mammalian sys- tems, and he continues to develop research tools to advance understanding of epigenetic mechanisms of gene control.
Dr Kan Saito has been a Research and Development Scientist at EMD Millipore since 2007. Currently, he is in charge of the development of kits and reagents
Drug Discovery World Fall 2011 35
for RNA-binding protein immunoprecipitation (RIP) in Dr John Rosenfeld’s group. Prior to joining EMD Millipore, Dr Saito was Seinor Postdoctoral Fellow in Dr Tomas Mustelin’s laboratory at Burnham Institute for Medical Research. Dr Saito also performed a postdoctoral study in Dr Jean- Pierre Kinet’s laboratory at Harvard Medical School as a research fellow of the Japan Society for the Promotional Science (JSPS) after he received a PhD in molecular biology from Tokyo Medical and Dental University. Dr Saito’s research has been focused on signal transduction mechanisms and gene regulation mechanism of immune systems, and is now focusing on the development of next genera- tion research tools for biological study, particularly in the emerging mechanisms of epigenetic and post transcriptional regulation.
Dr Michael R. Sturges has served as Senior Product Manager for Epigenetics at EMD Millipore since 2009. For the past 10 years he has worked in the bioscience industry in marketing and product devel- opment. This experience is complemented by more than 12 years of hands-on scientific research at both academic and commercial organisations. Dr Sturges earned his PhD at the University of California, Santa Cruz, and conducted his postdoc- toral studies in the Department of Pediatrics in the laboratory of Dr Charles Roberts Jr at Oregon Health and Sciences University in Portland Oregon. Dr Sturges is currently applying his experience and knowledge of genomics, proteomics and molecular biology to drive the development of improved and novel kits, assays, antibodies and proteins that enable epigenetic research.
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