Position Title
Professor Emeritus, Department of Internal Medicine
Professor Emeritus
Education
- 1958 B.A., History, Stanford University
- 1962 M.D., University of Rochester School of Medicine
- 1962-63 Internship in Medicine, Cleveland Metropolitan General Hospital
- 1963-65 Assistant Resident in Medicine, Cleveland Metropolitan General Hospital
- 1965-66 Chief Resident in Medicine, Cleveland Metropolitan General Hospital
- 1968-70 Fellow in Gastroenterology, The Johns Hopkins Hospital, Baltimore
Research Interests
The main focus of Dr. Halsted’s research is the regulation of alcoholic liver injury by hepatic methionine metabolism. Previous work established the mechanisms for folate absorption from the intestine, including characterization of a novel enzyme glutamate carboxypeptidase, as well the effects of alcoholism on folate metabolism in humans and animal models. Over the past 20 years, his laboratory established a pig model for alcoholic liver disease and demonstrated that chronic ethanol feeding reduces folate absorption and liver levels while inducing abnormal folate dependent methionine metabolism and liver injury. Most recent studies in an ethanol fed mouse model show that abnormal methionine metabolism alters the epigenetic control of genes that result in liver injury.
Certifications
- American Board of Internal Medicine, 3/20/70 (recertification 10/29/77)
- American Board of Internal Medicine, Subspecialty of Gastroenterology, 10/16/73
- American Board of Nutrition, Specialist in Human and Clinical Nutrition, 5/2/84
Selected Publications
Medici V, Peerson J, Stabler SP, French SW, Gregory JF, Virata MC, Albanese A, Bowlus CL, Devaraj S, Panacek EA, Rahim N, Richards JR, Rossaro L, Halsted CH. Impaired homocysteine transsulfuration is an indicator of alcoholic liver disease. J Hepatology 2010 In Press. [PubMed]
Esfandiari F, Medici V, Jose S, Wong DH, Dolatshahi M, Quinlivan E,Dayal S, Lentz SR, Tsukamoto H, Zhang YH, French SW, Halsted CH. Epigenetic regulation of hepatic endoplasmic reticulum stress pathways in the ethanol-fed Cystathionine βeta Synthase deficient mouse. Hepatology. 2010;51;932-941. [PubMed]
Zivkovic AM, German JB, Esfandiari F, Halsted CH. Quantitative lipid metabolomic changes in alcoholic micropigs with fatty liver disease. Alcoholism: Clinical and Experimental Research 2009;33:751-758. [PubMed]
Villanueva JA, Esfandiari F, White ME, Devaraj S, French SW, Halsted CH. S-adenosylmethionine (SAM) attenuates oxidative liver injury in micropigs fed ethanol with a folate deficient diet. Alcoholism: Clinical and Experimental Research 2007;31:1934-1943. [PubMed]
Esfandiari F, Villanueva JA, Wong DH, You,M, French SW, Halsted CH. S-adenosylmethionine (SAM) attenuates hepatic lipid synthesis in micropigs fed ethanol with a folate deficient diet. Alcoholism: Clinical and Experimental Research 2007. 31:1231-1239. [PubMed]
Villanueva JA, Esfandiari F, Wong DH, Ahmad I, Melnyk S, James SJ, Halsted CH. Abnormal transsulfuration and glutathione metabolism in the micropig model of alcoholic liver disease. 2006; Alcoholism: Clinical and Experimental Research, 30: 1262-1270. [PubMed]
Esfandiari F, Villanueva JA., Wong D, French SW, Halsted CH. Chronic Ethanol Feeding and Folate Deficiency Activate Hepatic Endoplasmic Reticulum Stress Pathway in Micropigs. American Journal of Physiology; Gastrointestinal and Liver Physiology. 2005; 289: G54-G63. [PubMed]
Villanueva JA, Halsted CH. Hepatic transmethylation reactions in micropigs with alcoholic liver disease. Hepatology 2004; 39: 1303-1310. [PubMed]
Halsted CH, Villanueva JA, Devlin AM, Parkkila S, Niemelä O, Garrow TA, Wallock LM, Shigenaga M, Melnyk S, James SJ. Folate deficiency disturbs hepatic methionine metabolism and promotes liver injury in the ethanol-fed micropig. Proceedings of the National Academy of Science 2002;99:10072-10077. [PubMed]
Halsted CH, Villanueva J, Chandler CJ, Stabler SP, Allen RH, Muskhelishvili L, James SJ, Poirier L. Ethanol feeding of micropigs alters methionine metabolism and increases hepatocellular apoptosis and proliferation. Hepatology 1996; 23:497-505. [PubMed]
Niemelä O, Parkkila S, Yla-Herttuala S, Villanueva J, Ruebner B, Halsted C. Sequential acetaldehyde production, lipid peroxidation, and fibrogenesis in micropig model of alcohol-induced liver disease. Hepatology 1995; 22:1208-14. [PubMed]
Villanueva J, Chandler CJ, Shimasaki N, Tang A, Nakamura M, Phinney SD, Halsted CH. Effects of ethanol feeding on liver, kidney, and jejunal membranes in micropigs. Hepatology 1994; 19:1229-40. [PubMed]
Nakamura MT, Tang AB, Villanueva J, Halsted CH, Phinney SD. Selective reduction of 6 and 5 desaturase activities but not 9 desaturase in micropigs chronically fed alcohol. J Clin Invest 1994; 93:450-54. [PubMed]
Halsted CH, Villanueva J, Chandler CJ, Ruebner B, Munn RJ, Parkkila S, Niemelä O. Centrilobular distribution of acetaldehyde and collagen in the ethanol-fed micropig. Hepatology 1993; 18:954-60. [PubMed]