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Name, Field, Position, Department, and Keyword |
Faculty associated with: Anna E. Beaudin Keywords: Cell and Molecular Neuroscience (23), Development (21), Genetics (9) Numerous genetic and nutritional epidemiological studies have demonstrated an association between impaired folate metabolism and risk for certain developmental anomalies including neural tube defects (NTDs). These disorders are common and potentially preventable in all human populations, however little is known about the biochemical mechanisms that regulate folate metabolism, or the role of altered folate metabolism in the initiation or progression of these disorders. The Stover laboratory focus on understanding how impairments in the metabolism of folic acid and other B-vitamins, due to nutritional deficiencies or genetic variations, alter DNA stability and expression, and how these alterations in DNA function cause disease and developmental anomalies. Folate-dependent one-carbon metabolism is required for the synthesis of purines, thymidylate and S-adenosylmethionine. Impairments in folate metabolism result from nutritional deficiencies or common and highly penetrant single nucleotide polymorphisms and increase risk for birth effects. Impairments in folate metabolism affect genome integrity, and the regulation of about 10% of mammalian genes whose transcription is regulated by cytosine and histone methylation. The Stover laboratory has recently identified new pathways for the regulation of folate metabolism and folate accumulation and the regulation of cellular methylation reactions. We have generated a number of gain-of-function and loss-of-function murine model systems to study folate metabolism during development. These model systems are used to quantify the effects of altered folate metabolism on genomic outcomes including methylation, transcription, mutation rates, and pathologic outcomes including neural tube defects and cancer. The laboratory employs a number of experimental techniques including stable isotope metabolic tracer studies to quantify metabolic flux, mass spectrometry to quantify genome integrity (uracil and methylcytosine content), and expression profiling using cDNA and oligonucleotide microarrays. These approaches, integrated with standard molecular biology and biochemical techniques, enable us to investigate the regulation of folate metabolism and comprehensively address the interactions among metabolic and genomic pathways in human health and disease. |
Graduate Student associated with: Patrick J. Stover, Barbara J. Strupp Keywords: Development (21), Hippocampus (11), Learning and Memory (13), Mouse (11), Neurogenesis (7) My interests lie in understanding the role of folate-based one carbon metabolism in central nervous system function, and more specifically in elucidating the molecular mechanisms that account for known associations between impairments in folate metabolism and disrupted neural development and neural function. |
Faculty associated with: Stephane A. Beaudin, Anna E. Beaudin, Tara L. Benedetto Keywords: Aging (6), Behavioral genetics (7), Cognitive Neuroscience (17), Genetics (9), Hippocampus (11), Learning and Memory (13), Mouse (11), Social behavior (12), Stress (8) In my lab, we are using rodent models to study human developmental cognitive disorders. This research is designed to identify the specific cognitive and affective processes that are affected and link these with underlying neural changes. The ultimate goals are to improve therapeutic intervention and elucidate basic brain-cognition relationships. Two projects, concerning prenatal cocaine exposure and early lead exposure, utilize rat models, whereas three other projects involve genetically manipulated mouse models of human disorders. These three projects deal with, respectively, mouse models of Down syndrome (the Ts65Dn mouse, which has a partial trisomy of chromosome 16),Fragile X syndrome (the fmr1 "knockout" mouse), and mice with a mutation in an enzyme involved in folate metabolism, to further investigate the role of folate alterations in neurogenesis and aging-related cognitive decline. We have recently discovered that perinatal supplementation with excess choline results in lasting cognitive benefits in the Down syndrome (DS) mouse model. This finding suggests that perinatal choline supplementation might significantly reduce the cognitive dysfunction seen in DS as well as reduce the risk of Alzheimer's Disease and age-related cognitive decline in the population at large. We are currently investigating the neural bases of this striking benefit. Also visit my Research/Photo Gallery entry |
Please report corrections, questions, comments, and problems to: Lori Miller (lmm8 AT cornell.edu)