Alcohol abuse is the single most common known and preventable cause of birth defects, and a major contributor to both chronic liver disease and neurodegeneration in the United States. Our research has linked several chronic alcohol exposure-mediated abnormalities in brain and liver function to impairments in insulin and insulin-like growth factor signaling, particularly with regard to cell survival and energy metabolism. However, in order to capitalize on these recent gains, it will be necessary to extend the analyses to human disease states using state-of-the-art methodology. The major goals of this proposal are to: 1) investigate mechanisms of alcohol-mediated neurodegeneration in adult human brains using molecular and biochemical approaches;2) provide a strong, highly supportive environment to train and mentor junior investigators, particularly physician-scientists, to investigate human disease mechanisms by utilizing current technology to analyze human tissue samples;and 3) educate junior investigators about the importance of experimental models for testing hypotheses and validating results from human studies. Emphasis will be placed on including women and minority trainees. Suzanne M. De la Monte is a Pathologist and Neuropathologist by training and clinical activities at the Rhode Island Hospital, and Professor of Pathology and Clinical Neuroscience at Brown University. Dr. De la Monte has a long track record of training young investigators in human disease, biomedical, and translational research. Her laboratory, which currently is supported by NIH funding from NIAAA, hosts several trainees including undergraduates, medical students, graduate students, postdoctoral fellows, and junior physician-scientists, most of whom are women or members of under-represented minority groups. This Mid-career investigator award will provide better opportunity for Dr. De la Monte to exercise leadership and high quality mentorship and training of promising young scientists. The information included in this application demonstrates a productive career in human and translational research, and demonstrates Dr. De la Monte's commitment to continuing this type of work while mentoring scientists for the future.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Special Emphasis Panel (ZAA1-DD (51))
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Grandison, Lindsey
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Rhode Island Hospital
United States
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Ramirez, Teresa; Longato, Lisa; Dostalek, Miroslav et al. (2013) Insulin resistance, ceramide accumulation and endoplasmic reticulum stress in experimental chronic alcohol-induced steatohepatitis. Alcohol Alcohol 48:39-52
Mellion, Michelle L; Nguyen, Vananh; Tong, Ming et al. (2013) Experimental model of alcohol-related peripheral neuropathy. Muscle Nerve 48:204-11
de la Monte, Suzanne M; Tong, Ming; Bowling, Nathaniel et al. (2011) si-RNA inhibition of brain insulin or insulin-like growth factor receptors causes developmental cerebellar abnormalities: relevance to fetal alcohol spectrum disorder. Mol Brain 4:13
Gundogan, Fusun; Bedoya, Armando; Gilligan, Jeffrey et al. (2011) siRNA inhibition of aspartyl-asparaginyl ?-hydroxylase expression impairs cell motility, Notch signaling, and fetal growth. Pathol Res Pract 207:545-53
Setshedi, Mashiko; Longato, Lisa; Petersen, Dennis R et al. (2011) Limited therapeutic effect of N-acetylcysteine on hepatic insulin resistance in an experimental model of alcohol-induced steatohepatitis. Alcohol Clin Exp Res 35:2139-51
Gundogan, Fusun; Elwood, Gwen; Mark, Princess et al. (2010) Ethanol-induced oxidative stress and mitochondrial dysfunction in rat placenta: relevance to pregnancy loss. Alcohol Clin Exp Res 34:415-23
Setshedi, Mashiko; Wands, Jack R; Monte, Suzanne M de la (2010) Acetaldehyde adducts in alcoholic liver disease. Oxid Med Cell Longev 3:178-85
Brennan-Krohn, Thea; Salloway, Stephen; Correia, Stephen et al. (2010) Glial Vascular Degeneration in CADASIL. J Alzheimers Dis :
de la Monte, Suzanne M; Tong, Ming; Nguyen, VanAnh et al. (2010) Ceramide-mediated insulin resistance and impairment of cognitive-motor functions. J Alzheimers Dis 21:967-84
de la Monte, Suzanne M; Wands, Jack R (2010) Role of central nervous system insulin resistance in fetal alcohol spectrum disorders. J Popul Ther Clin Pharmacol 17:e390-404

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