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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24AA016126-05
Application #
7826917
Study Section
Special Emphasis Panel (ZAA1-DD (51))
Program Officer
Grandison, Lindsey
Project Start
2006-05-20
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2012-04-30
Support Year
5
Fiscal Year
2010
Total Cost
$148,889
Indirect Cost
Name
Rhode Island Hospital
Department
Type
DUNS #
075710996
City
Providence
State
RI
Country
United States
Zip Code
02903
de la Monte, Suzanne M; Tong, Ming (2014) Brain metabolic dysfunction at the core of Alzheimer's disease. Biochem Pharmacol 88:548-59
de la Monte, Suzanne M (2014) Type 3 diabetes is sporadic Alzheimer׳s disease: mini-review. Eur Neuropsychopharmacol 24:1954-60
Mellion, Michelle L; Silbermann, Elizabeth; Gilchrist, James M et al. (2014) Small-fiber degeneration in alcohol-related peripheral neuropathy. Alcohol Clin Exp Res 38:1965-72
Lizarazo, Diana; Zabala, Valerie; Tong, Ming et al. (2013) Ceramide inhibitor myriocin restores insulin/insulin growth factor signaling for liver remodeling in experimental alcohol-related steatohepatitis. J Gastroenterol Hepatol 28:1660-8
Tong, Ming; Ziplow, Jason; Chen, William Cy et al. (2013) Motor Function Deficits Following Chronic Prenatal Ethanol Exposure are Linked to Impairments in Insulin/IGF, Notch and Wnt Signaling in the Cerebellum. J Diabetes Metab 4:238
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 (2012) Therapeutic targets of brain insulin resistance in sporadic Alzheimer's disease. Front Biosci (Elite Ed) 4:1582-605
De La Monte, S M (2012) Metabolic derangements mediate cognitive impairment and Alzheimer's disease: role of peripheral insulin-resistance diseases. Panminerva Med 54:171-8
de la Monte, Suzanne M; Re, Edward; Longato, Lisa et al. (2012) Dysfunctional pro-ceramide, ER stress, and insulin/IGF signaling networks with progression of Alzheimer's disease. J Alzheimers Dis 30 Suppl 2:S217-29

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