Welcome Dr. Karen Usdin and Dr. Pietro Chiurazzi to CFXF's Board of Scientific Advisors

CFXF is very proud of the small group of dedicated researchers that graciously and wisely inform all our technical decisions. Each of them possesses a unique professional commitment to finding a cure for fragile X and as CFXF Scientific Advisors, they give a bit extra to the fragile X community. We rely on them to help us make the best decisions about our research awards and they never let us down. We are very pleased to start off the New Year by welcoming our two newest Scientific Advisors, Dr. Usdin and Dr. Chiurazzi.

Dr. Karen Usdin received her Ph.D. in 1986 from the University of Cape Town, South Africa. After doing Post-Doctoral work on gene regulation in bacteria and a family of endogenous retrovirus-like elements in mammals, she turned her attention to the Repeat Expansion diseases, a group of genetic disorders that includes fragile X syndrome. She is now a Senior Investigator in the Laboratory of Molecular and Cellular Biology at the National Institutes of Health, U. S. A. Her group is investigating the mechanism responsible for the fragile X mutation. They are also interested in the molecular basis of the premature ovarian failure seen in some female carriers of “premutation” alleles and the tremor and ataxia seen in some male carriers. In addition, they are trying to understand the molecular events that lead to the transcriptional silencing of the FMR1 gene in people with fully mutated alleles. Their work involves the analysis of DNA and RNA structures formed by the fragile X gene as well as the proteins that bind to them. Her group has also developed a number of cell and animal models for studying different aspects of fragile X syndrome. It is hoped that these models may provide new insights into the normal and pathological regulation of the FMR1 gene, and may one day provide good systems for testing potential treatments for this disorder.

Born in Rome in 1967, Dr. Pietro Chiurazzi earned his undergraduate degree in 1992 with a thesis on the molecular diagnosis of fragile X syndrome. He earned his M.D. in 1996 at the Catholic University in Rome, specializing in Medical Genetics with research on the origin of FMR1 full mutations in the population (founder effect). He earned a Doctorate in Genetics in October 2001 at the Erasmus University of Rotterdam (The Netherlands), defending a thesis on the in vitro re-activation of the fully mutated FMR1 gene with DNA demethylating agents and hyperacetylating drugs. Dr. Chiurazzi is an

SCIENTIFIC ADVISORS Robert Bauchwitz, M.D., Ph.D. Columbia University New York, NY Randi Hagerman, M.D. University of California at Davis M.I.N.D. Institute Pietro Chiurazzi, M.D., Ph.D. University Cattolica Rome, Italy Prof. Giovanni Neri University Cattolica Rome, Italy Jonathan Cohen, M.D. Monash University Melbourne, Australia Karen Usdin, Ph.D. National Institutes of Health Bethesda, MD Gideon Dreyfuss, Ph.D. University of Pennsylvania Philadelphia, PA Michael Tranfaglia, M.D. FRAXA Research Foundation Newburyport, MA Assam El-Osta, M.D. The Baker Institute Melbourne, Australia Haruhiko Siomi, Ph.D. Institute for Genome Research University of Tokushima Tokushima, Japan Brenda Finucane, M.S., C.G.C. Elwyn Training and Research Institute Media, PA Jason Dictenberg, Ph.D. Yeshiva University New York, New York

Associate Member of the Italian Association for Fragile X Syndrome. Since 1999, he has held a research position in the Department of Pediatrics at the University of Messina. In February of 2003, Dr. Chiurazzi returns to the Institute of Medical Genetics of the Catholic University in Rome and will continue his work to find a cure for fragile X.

MEET DR. YOLANDA DE DIEGO,
OUR NEWEST GRANTEE

Dr. Yolanda de Diego Otero, from the “Fundacion Hospital Carlos Haya” research laboratory, has been working on fragile X since 1993. Her first contribution was a fragile X screening on the mentally retarded population in Andalucia (Southern Spain). This was the main subject for her doctoral thesis, developed at the University of Seville where she obtained a Ph.D. in 1997. Subsequently, she was awarded a grant from the highly prestigious and competitive European Marie Curie Postdoctoral Research Programme. She started to work as research fellow at the Clinical Genetics Department of the Erasmus University Rotterdam, under the supervision of Prof. Ben Oostra and Dr. Rob Willemsen. During the first year her project was focused on the FMRP and FXRP family localization in the mouse embryonic development, and the FMRP transport on the neurites during the second year, publishing the results in prominent journals. Molecular and Cellular Biology published her most recent results.

After two and a half years abroad, she was awarded another Marie Curie Postdoctoral grant to return to the University of Malaga (Spain), now on a new approach, the Oxidative Stress on the Fragile X mouse model using the FMR1 knockout mouse she brought from Rotterdam.

Dr. de Diego’s results were focused on biochemical and pharmacological studies. Initially, she observed the increase level on the oxidative stress in the brain and testes of the knockout mice, as they are the main organs affected by fragile X syndrome. The next step was to perform a treatment trial to try the normalization of the oxidative status. For the trial she used a neuroprotector antiperoxidative methodology to treat the mice and to normalize the biochemical parameters (lipid peroxidation, glutathione level and antioxidant enzymes). The most striking observation was the normalization in the testicle size after one month of treatment. This project was done in 2001 and after finishing this first part, the next goal was a psychopharmacological study to demonstrate the effectiveness of the treatment in the improvement of the learning and behavioral deficits observed in the mouse model correlated with that observed in the patients.

At that time, Dr. de Diego received a position as a senior investigator at the “Fundacion Hospital Carlos Haya”, working in the group led by Dr. Fernando Rodriguez de Fonseca (Head of the Research Unit and Director of the Foundation). The group has wide and well-known experience in neuropsychopharmacological studies as it could be certified for its articles in high impact journals such as Nature, Science and the Journal of Neuroscience.

The experience of Dr. de Diego Otero in the fragile X field, the wide knowledge of Dr. Rodriguez de Fonseca on Psychopharmacological studies, and the support of Conquer Fragile X Foundation represent an extraordinary and fruitful collaboration that come together in this promising project. Hopefully, findings from this project will highlight a new step in drawing a specific treatment for fragile X patients