When the Intellectual and Developmental Disabilities Research Center (IDDRC) at Baylor College of Medicine (BCM) was established in August of 1988, neurology had not yet benefited from the newly emerging tools of genetics. The field had yet to determine what mutations caused even the most common forms of mental retardation and developmental delay or how we might go about treating such disorders. The IDDRC at BCM created an infrastructure of core facilities to support investigators interested in identifying the causes of mental retardation and dissecting the pathogenesis of various human conditions that lead to disability. These cores have been instrumental to the remarkable discoveries that were to come.
The IDDRC at BCM currently supports the research of over 40 investigators studying abnormalities in human development. The joint benefits of improved diagnosis, better patient care, and deeper understanding of human biology have come directly from IDDRC support for research leading to the discovery of the molecular basis of Stargardt syndrome, Miller-Dieker syndrome, glycerol kinase deficiency, 1p36 deletion syndrome, Smith-Magenis disease, Prader-Willi Syndrome and Angelman Syndrome, among others. The IDDRC at BCM has been a crucial player in all these discoveries, and BCM’s technological advances — multicolor FISH, genetic engineering in the mouse, shot-gun cloning and large-scale sequencing —have in turn strengthened the ability of the cores to support BCM’s research endeavors and laid the groundwork for BCM’s Human Genome Sequencing Center. The cores for neuropathological analysis, embryonic stem cell work, generating transgenic mice and performing neurobehavioral and synaptic plasticity analyses (to name a few) concentrate expertise and make it accessible to investigators who would otherwise have to find ways to import these technologies and develop these skills in their own labs. The IDDRC is an impressive venue for facilitating research in a cost-efficient way.
Successes of the IDDRC at Baylor College of Medicine (BCM)
The combination of these research accomplishments and an interactive group of IDDRC investigators created a clear identity for Intellectual and Developmental Disabilities (IDD) research at Baylor College of Medicine (BCM). BCM faculty have made numerous contributions towards understanding the etiology and pathogenesis of several leading causes of MRDD and are recognized as leading experts for these disorders. The labs of David Nelson Ph.D., James Lupski M.D., Ph.D., and Huda Zoghbi M.D. are a few examples that have been highlighted to demonstrate some of the IDDRC successes.
Dr. Nelson and his collaborators discovered the dynamic nature of the Fragile X mutation, which provided an elegant explanation for the increasing severity of the disease upon transmission to another generation. Further studies on trinucleotide repeats at BCM not only allowed the identification of numerous disease genes, such as those causing myotonic dystrophy, Friedreich’s ataxia and several spinocerebellar ataxias, but lent insight into the mechanisms contributing to triplet repeat instability and disease pathogenesis.
Another important success story is Dr. Lupski’s discovery that single gene dosage can be as important (and liable to disruption) as sequence integrity. His studies of the dosage-sensitive myelin gene PMP22 led to the discovery that duplications and deletions are caused by aberrant recombination between repeated sequences. Such a mechanism has now been shown to account for deletions in other disorders such as Williams syndrome, Smith-Magenis syndrome, velocardiofacial syndrome, and type 1 neurofibromatosis. The realization that these “genomic disorders” are a rather common source of MR and DD has led to new efforts to identify additional such repeats as candidates for similar mutations.
The discovery in the Zoghbi Lab of the genetic basis of Rett syndrome made clear the importance of epigenetic modifications in brain function. Disruptions in MeCP2 turn out to be responsible not only for Rett syndrome, one of the most common causes of mental retardation, but also for a broad spectrum of phenotypes ranging from autism, non-syndromic retardation or affective disorders to neonatal encephalopathy. The IDDRC cores have allowed BCM scientists to generate and characterize a remarkable mouse model of this disease. Work on UBE3A in the Dr. Arthur Beaudet's laboratory is probing the epigenetic pathways controlling neuronal function and integrity in Angelman Syndrome and Autism.
Huda Zoghbi, M.D. was appointed director in 1994 upon recommendation of the internal advisory committee after Dr. Edward McCabe, BCM IDDRC founding principal investigator and director, left BCM to chair pediatrics at UCLA. Dr. Zoghbi has been director of the BCM IDDRC for over fourteen years and will continue in that capacity. She is a board certified pediatric neurologist with abundant research accomplishments. She brings interest in and experience with numerous human genetic disorders with mental retardation as a component. She has a particular interest in Rett syndrome. Dr. Zoghbi is professor of pediatrics, neurology, neurosciences, and molecular and human genetics as well as an investigator of the Howard Hughes Medical Institute (HHMI).
IDDRC Associate Director
David Nelson, Ph.D. is the associate director of the BCM IDDRC, and will continue in that role in this proposed renewal. Dr. Nelson is a human molecular geneticist who brings extensive experience and interest in mental retardation to the IDDRC through his activities in characterizing the Fragile X syndrome, FRAXE syndrome and Incontinentia Pigmenti genes and their products. He also has prior experience in managing large centers as both associate director and director of the National Institutes of Health (NIH) funded BCM Human Genome Sequencing Center (BCM-HGSC). Dr. Nelson will be responsible for the BCM-IDDRC should the director become incapacitated and he will continue to advise and assist the director in the operation of the IDDRC along with the Administrative and Scientific Advisory Committee (ASAC).
The internal Administrative and Scientific Advisory Committee (ASAC) assists the director and associate director with long-term planning, operations and policy issues within the BCM-IDDRC. The members of this committee are:
Morey Haymond, M.D. - Professor and Acting Chair of Pediatrics and expert on childhood diseases, who was previously director of the Child Health Research Center.
William Brinkley, Ph.D. - Vice President for Graduate Sciences and Dean of the Graduate School of Biomedical Sciences.
The members of the advisory committee are knowledgeable in administrative aspects of the college and active members in strategic planning efforts aimed at advancing both basic and clinical research at BCM. Members of the ASAC as well as other members of BCM administration are committed to enhancing the scope of IDD research at Baylor as evident by the school's investment in developing the Human Neuroimaging Laboratory.