Personal Information

Name
Hidekazu Tsukamoto

Business Address
Department of Medicine
1355 San Pablo Street, AHC-125
Los Angeles, CA 90033-4581

Business Telephone
(323) 442-5107
FAX #: (323) 442-5567

Education

High School: Komaba-Toho High School, Tokyo, Japan, 1971

University: Nippon Veterinary & Animal Science University; Japan, D.V.M., 1975

Graduate School: University of California, Davis, M.S. in ComparativePathology, 1980
UC Davis/Kobe University School of Medicine, Kobe, Japan, Ph.D. in Cell Biology/Medical Science, 1988

Research Fellowship: Department of Veterinary Surgery, Nippon Veterinary & Animal Science University, Tokyo, Japan, April 1975-March 1976
Department of Medicine, University of California, Davis,July 1981-June 1983

Professional Background

Academic appointments

Assistant Research Professor of Medicine, University of California, Davis, 1984-1990
Adjunct Assistant Professor of Medicine, University of California, Davis, 1990-1991
Associate Professor of Medicine and Nutrition, Case Western Reserve University, 1991-1994
Professor of Medicine, University of Southern California (USC), 1994-1996
Professor of Medicine and Pathology with Tenuer, USC, 1996-present

Specific teaching responsibilities

Co-course leader, Gastro-290, "Frontiers in Basic Gastrointestinal and Liver Research" for medical students, residents, GI fellows, andgraduate students, 1989-1991
Co-program director, "Frontiers in Gastroenterology and Hepatology" for GI fellows, 1991-1994
Lectures on cell and molecular biology of alcoholic liver fibrogenesis for first year medical students, 1992-1994
Program director, "Frontiers in Clinical and Basic Sciences", 1995-present
Faculty lecturer, Pathology #570, Graduate student seminar in pahtology, 1997-
Co-course leader, Pathology #599, Special Topic (Frontiers in Basic and Applied Sciences), 1997-

Specific administrative responsibilities

Member, Research and Development Committee and Animal Studies Subcommittee, University of California, Davis/ Martinez VA Med Ctr, 1985-1991
Research Director, Department of Medicine, Case Western Reserve University at MetroHealth Med Ctr, 1991-1993
Chairman, Department of Medicine Research Committee, Case Western Reserve University at MetroHealth Med Ctr, 1991-1993
Member, Research Advisory Committee, MetroHealth Med Ctr, 1992-1994
Associate Director, USC Liver Disease Research Center, 1994-present

Other Professional activity

Ad Hoc reviewer for NIH and VA Merit Review Board proposals, 1987-1994
Member, Special Review Committee, Biomedical Center Application, NIH/NIAAA, 1990, 1995
Member, NIH/NIAAA Biochemistry, Physiology and Medicine Subcommittee, Alcohol Biomedical Research Committee, 1994-1998
Member, DRG, NIH Alcohol and Toxicology Study Section Panel-4, 1996-1998
Ad Hoc member, VA Merit Review Board for Gastroenterology, 1995, 1996
Member, VA Merit Review Board for Gastroenterology, 1997-2000
Member, AASLD Abstract Selection Committee, 1995-1997
Member, Editorial Board for Hepatology, 1997-
Member, Editorial Board for Americal Journal of Physiology: Gastrointestinal Physiology, 1997-
Ad hoc manuscript reviewer for Hepatology, Gastroenterology, Journal of Clinical Investigation, American Journal of Physiology, Liver, Alcoholism: Clinical and Experimental Research
Research Physiologist, Department of Veterans Affairs, 1984-present

Society Memberships

Local: None

National

American Association for Studies of Liver Diseases, 1986 - American Association of Advancement of Science, 1986 - American Veterinary Medical Association, 1986 - Research Society on Alcoholism, 1992 - Americal Physiological Society, 1997-

Consultantships

Consultant, East Bay Institute for Research and Development, Martinez, CA, 1990-1991

Research Activities

Complete Bibliography

Appended

Major Area of Research Interest

Pathogenesis of alcoholic liver injury and fibrogenesis with special interest in cell and molecular biology of non-parenchymal live cells.

Research in progress

Pathogenesis of progressive alcoholic liver injury. Cellular and molecular mechanisms of Ito cell activation in liver fibrosis.

Research Grants in Past Five Years

1. Pathogenesis of progressive alcoholic liver injury. $402,000 NIH/NIAAA RO1 AA06603-6~10, 1989-1993, Principal Investigator

2. Regulation of serum protein composition in nephrosis. $132,000 NIH/NIDDK, 1990-1991, Co-Investigator (PI: Dr. George Kaysen)

3. Regulation of albumin metabolism in nephrotic syndrome. $100,000 VA Merit Review Board, 1990-1991, Co-Investigator (PI: Dr. George Kaysen)

4. Cellular and molecular mechanisms of Ito cell activation in $163,000 liver fibrosis. VA Merit Review Board, 1991-1993, Principal Investigator

5. Cellular and molecular mechanisms of Ito cell activation in $330,000 liver fibrosis. VA Merit Review Board, 1993-1996, Principal Investigator

6. Cellular and molecular mechanisms of Ito cell activation in $481,200 liver fibrosis. VA Merit Review Board, 1996-2000, Principal Investigator

7. Pathogenesis of Progressive alcoholic liver injury. $1,500,000 NIH/NIAAA Merit Award R37 AA06603, 1993-2003, Principal Investigator

8. Mechanism of Ethanol-Induced Pancreatitis. $579,580 NIH R01 DK50217, 1995-1998, Co-Principal Investigator

9. Oral Iron Chelator Predicated on Desferrithiocin. $2,172,765 NIH R01 DK49108, 1995-2000, Co-Investigator (PI: Dr. Raymond Bergeron)

Extramural Invited Lectures and Seminars

June 5, 1997 International Symposium on Oxidative Stress: Biochemistry and Pathophysiology, Barcelona, Spain. "Role of NF-kB in activation of Kupffer cells in Liver Injury"

February 19, 1997 University of North Carolina at Chapel Hill, Skipper Bowles Honorary Lectureship: "Intragastric Ethanol Infusion Model: Insights into Pathogenesis of Alcoholic Liver Disease"

December 17, 1998 Cedars Sinai Medical Center, Department of Surgery. "Role of Kupffer and Hepatic Stellate Cells in Chronic Liver Disease"

August 27, 29, 1996 Institute of Clinical Chemistry, University of Ulm, Germany, Visiting Professorship: "Ethanol, CCK, and Pancreas" and "Role of Oxidative Stress in Activation of Kupffer and Hepatic Stellate Cells in Liver Injury.

March 22, 1996 Habor-UCLA Medical Center, Department of Pathology Ground Rounds: Insights into Activation of Hepatic Stellate Cells in Liver Fibrosis.

September 5, 1995 Karolinska Instutute, Department of Pharmacology, Stockholm, Sweden: Experimental Alcoholic Fibrogenesis: Cell and Molecular Biology.

September 8, 1995 European Society for biomedical Research on Alcoholism, Stuttgart, Germany: Intragastric Ethanol Infusion Model.

September 11, 1994 A Satellite Symposium to the 7th International Symposium of the Cells of the Hepatic Sinusoid, Tokyo, Japan: Role of Oxidative Stress in Activation of Kupffer and Ito Cells in Liver Fibrogenesis.

October 26, 1993 Alcohol Research Center, VA Medical Center/University of Nebraska, Omaha, Nebraska: Insights into cellular and molecular mechanisms of alcoholic liver fibrosis.

September 23, 1993 Division of Digestive Diseases and Nutrition, University of North Carolina at Chapel Hill: Cellular Mechanisms of Alcoholic Liver Fibrogenesis.

September 13, 1993 NIH/NIAAA Division of Basic Science, "Activation of Ito Cells in Alcoholic Liver Fibrosis: Role of Kupffer Cells and Lipid Peroxidation"

July 1, 1993 Falk Symposium No. 71, Fat-Storing Cells and Liver Fibrosis, Florence, Italy, "Activation of Fat Storing Cells in Alcoholic Liver Fibrosis: Role of Kupffer Cells and Lipid Peroxidation"

June 24, 1993 Research Society on Alcoholism Meeting, San Antonio, Texas, Chaired Workshop, "Rat Intragastric Ethanol Infusion Model: Current Progress in Studies on Alcohol-Induced Organ Injury"

September 14, 1992 The University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu, Japan; "Pathogenesis of Alcoholic Liver Disease"

June 15, 1992 Research Society on Alcoholism Meeting, La Jolla, California, Chair and Co-chair for "Alcoholic Liver Disease Pathogenesis" and "Alcohol and Liver"

May 4, 1992 NIH/NIAAA Extramural Science Advisory Board Conference, Washington, D.C.; "A Model of Alcoholic Liver Fibrosis: Genetic Application"

February 1, 1992 Japanese Society for Biomedical Research of Alcohol and Alcoholism, Tokyo, Japan; "Cellular and Molecular Mechanisms of Alcoholic Liver Fibrosis"

October 17, 1989 Department of Pathology, University of New Mexico; "Pathogenesis of Alcoholic Liver Disease"

July 2, 1988 Fourth Congress of the International Society for Biomedical Research on Alcoholism; "A Model of Ethanol-Induced Chronic Pancreatitis - Pathobiology in CCK Regulation of Pancreatic Acinus"

July 5, 1988 Symposium on Alcohol and Liver, Tokyo, Japan, "Incomplete Compensation of Hepatic Oxygen Consumption in Ethanol-Induced Centrilobular Liver Necrosis"

October 10, 1986 Department of Pharmacology, University of Toronto, "Rat Model of Ethanol-Induced Liver and Pancreatic Injury"

July 2, 1985 Department of Pathology, University of Ottawa, "Cyclic Pattern of Blood Alcohol Level - Influence of Blood Alcohol Level and Cyclic Amplitude on Alcoholic Liver Injury in Rat"

BIBLIOGRAPHY

1. Tsukamoto H, Parker HR, Gribble DH, Mariassy A, and Peoples SA: Nephrotoxicity of sodium arsenate in dogs. Am J Vet Res 44: 2324-2330, 1983.

2. Tsukamoto H, Parker HR and Peoples SA: Metabolism and renal handling of sodium arsenate in dogs. Am J Vet Res 44: 2331-2335, 1983.

3. Tsukamoto H, Lew G, Larkin EC, Largman C, and Rao GA: Hepatic origin of triglycerides in fatty livers produced by the continuous intragastric infusion of an ethanol diet. Lipids. 19: 419-422, 1984.

4. Tsukamoto H, Reidelberger R, French SW, and Largman C: Long-term cannulation model for blood sampling and intragastric infusion in the rat. Am J Physiol 247: R595-599, 1984.

5. Rao GA, Goheen SC, Tsukamoto H, and Larkin EC: Chronic alcohol consumption may not cause pancreatic steatosis in rats. IRCS Med Sci 12: 486-487, 1984.

6. Tsukamoto H, French SW, Benson N, Rao GA, Larkin EC, and Largman C: Severe and progressive steatosis and focal necrosis in rat liver induced by continuous intragastric infusion of ethanol and low fat diet. Hepatology 5: 224-232, 1985.

7. Tsukamoto H, French SW, Reidelberger R, and Largman C: Cyclical pattern of blood alcohol levels during continuous intragastric infusion in rats. Alcoholism Clin Exp Res 9: 31-37, 1985.

8. Tsukamoto H, Kiefer MA, Rao GA, Larkin EC, Largman C, and Sankaran H: Cholecystokinin-induced secretion and synthesis of amylase and cationic trypsinogen by pancreatic acini isolated from rats given an ethanol diet. Life Sci 37: 1359-1365, 1985.

9. Rao GA, Tsukamoto H, Larkin EC, and Derr RF: Nutritional inadequacy of diets for young growing rats used in models of chronic alcohol ingestion. Biochem Arch 1: 97-101, 1985.

10. Tsukamoto H, French SW, and Largman C: Correlation of cyclical blood alcohol levels with progression of alcoholic liver injury. Biochem Arch 1: 215-220, 1985.

11. Largman C, Reidelberger R, and Tsukamoto H: Correlation of trypsin-plasma inhibitor complexes with mortality of experimental pancreatitis in rats. Dig Dis Sci 31: 961-969, 1986.

12. Tsukamoto H, Delgado G, Reidelberger RD, and Largman C: Effects of cephalic stimuli, food intake and cholecystokinin on plasma levels of amylase, lipase, and immunoreactive cationic trypsinogen in Rats. Digestion 35: 69-77, 1986.

13. Tsukamoto H, Sankaran H, Delgado G, Reidelberger SW, and Largman C: Increased pancreatic acinar content and secretion of cationic trypsinogen following 30 day continuous ethanol intoxication in rats. Biochem Pharmacol 35: 3623-3629, 1986.

14. Tsukamoto H, Towner SJ, Ciofalo LM, and French SW: Ethanol-induced liver fibrosis in rats fed high fat diet. Hepatology 6: 814-822, 1986.

15. Fletcher TS, Tsukamoto H, and Largman C: Immunoenzymometric determination of trypsin/a1protease inhibitor complex in plasma of rats with experimental pancreatitis. Clin Chem 32: 1738-1741, 1986.

16. Inomata T, Rao GA, Tsukamoto H: Lack of evidence of increased lipid peroxidation in ethanol-induced centrilobular necrosis of rat liver. Liver 7: 233-239, 1987.

17. Peppin JF, Towner SJ, Matsuoka M, Kawasaki RI, Rao GA, and Tsukamoto H: Effects of sustained ethanol intoxication and optimal nutrition on free amino acid levels in plasma, liver and muscle of the rat. Nutr Res 8: 65-71, 1988.

18. Tsukamoto H, Towner SJ, Yu GSM, and French SW: Potentiation of ethanol-induced pancreatic injury by dietary fat - Induction of chronic pancreatitis by alcohol in rats. Am J Pathol 131: 246-257, 1988.

19. Tsukamoto H, Otsuki M, Baba S, Mizoi Y. Abnormal cholecystokinin-acinar function coupling in atrophied pancreatic acini from rats fed ethanol and a high fat diet. Jpn J Alcohol & Drug Depend 23: 332-350, 1988.

20. Tsukamoto H, and Xi XP: Incomplete compensation of enhanced hepatic oxygen consumption in rats with alcoholic centrilobular liver necrosis. Hepatology 9:302-306, 1989.

21. Tsukamoto H, Otsuki M, Baba S. Effects of chronic alcohol consumption on pancreatic acinar cell functions. Relationship to the amount of fat intake. Alcohol Metabolism Liver 8: 107-113, 1989.

22. Matsuoka M, Pham NT, and Tsukamoto H. Differential effects of interleukin-1a, tumor necrosis factor-a and transforming growth factor-b1 on cell proliferation and collagen formation by cultured fat-storing cells. Liver 9: 71-78, 1989.

23. Nanji AA, Tsukamoto H, and French SW. Relationship between fatty liver and subsequent development of necrosis, inflammation and fibrosis in experimental alcoholic liver disease. Exp Mol Pathol 51:141-148, 1989.

24. Dalessandri KM, Lantz BMT, Tsukamoto H, Link DP, and Brock J. Superior mesenteric artery vasoactivity in hyperlipidemic Watanabe rabbits versus normal lipidemic New Zealand controls. J Invest Surg 2: 471-477, 1989.

25. Dalessandri KM, Bogren H, Lantz BMT, Tsukamoto H, Bjorkerud S, and Brock J. Aortic compliance in hypercholesterolemic Watanabe rabbits compared to normal New Zealand controls. J Invest Surg 3: 245-251, 1990.

26. Matsuoka M, Zhang MY, and Tsukamoto H. Sensitization of hepatic lipocytes by high fat diet to stimulatory effects of Kupffer cell derived factors: Implication in alcoholic liver fibrosis. Hepatology 11: 173-182, 1990.

27. Tsukamoto H, Gaal K, and French SW. Insights into pathogenesis of alcoholic liver necrosis and fibrosis. Status report. Hepatology 12: 599-608, 1990.

28. Smith SM, Yu GSM, and Tsukamoto H. IgA nephropathy in alcohol abuse. An animal model. Lab Invest 62: 179-184, 1990.

29. Matsuoka M, Tsukamoto H. Stimulation of hepatic lipocyte collagen production by Kupffer cell derived transforming growth factor b: Implication for a pathogenetic role in alcoholic liver fibrosis. Hepatology 11:599-605, 1990.

30. Tsukamoto H, Matsuoka M, and French SW. Experimental models of hepatic liver fibrosis: a review. Seminars in Liver Disease 10: 56-65, 1990.

31. Matsuoka M and Tsukamoto H. Expression of transforming growth factor by rat Kupffer cells. Ann NY Acad Sci 593: 357-359, 1990.

32. Matsuoka M, Okumura M, Tsukamoto H. Functional activation of Ito cells in alcoholic liver fibrosis. Alcohol Metabolism Liver 9:138-141, 1990.

33. Dalessandri KM, Wedemeyer W, Tsukamoto H, Bogren H, Bjorkerud S, Tinker D, Rucker RB, Eisele P, Parker J, Brock J. The Watanabe hyperlipidemic rabbit as a model of aortic degeneration of the medial lamellar elastin unit. J Invest Surg 5: 19-23, 1992.

34. Kamimura S, Gaal K, Britton R, Bacon BR, Triadafilopoulos G, Tsukamoto H. Increased 4-hydroxynonenal levels in experimental alcoholic liver disease: association of lipid peroxidation with liver fibrogenesis. Hepatology 16: 448-453, 1992.

35. Castillo T, Koop DR, Kamimura S, Triadafilopoulos G, Tsukamoto H. Role of cytochrome P450 2E1 in ethanol- carbon tetrachloride- and iron-dependent microsomal lipid peroxidation. Hepatology 16: 992-996, 1992.

36. Smith SM, Tsukamoto H. Time dependency of IgA nephropathy induction in alcohol ingestion. Alcoholism Clin Exp Res 16: 471-473, 1992.

37. Smith SM, Tokuda S, Tsukamoto H. Mucosal immune dysfunction in alcoholic IgA nephropathy. Clin Immun Immunopath 64: 205-209, 1992.

38. Hirano T, Kaplowitz N, Tsukamoto H, Kamimura S, Fernandez-Checa J. Hepatic mitochondrial glutathione depletion and progression of experimental alcoholic liver disease in rats. Hepatology: 16:1423-1427, 1992.

39. Horne W, Tsukamoto H. Rat intragastric ethanol infusion model: Current progress in studies on alcohol-induced organ injury. Dietary modulation of alcohol-induced pancreatic injury. Alcohol 10:481-484, 1993.

40. Tsukamoto H. Oxidative Stress, Antioxidants, and Alcoholic Liver Fibrogenesis. Alcohol 10:465-467, 1993.

41. Tsukamoto H, French SW. Evolution of Intragastric Ethanol Infusion Model. Alcohol 10: 439-441, 1993.

42. Fernandez-Checa, JC, Hirano T, Tsukamoto H, Kaplowitz N. Mitochondrial glutathione depletion in alcoholic liver disease. Alcohol 10: 469-475, 1993.

43. Malecka-Panas E, Triadafilopoulos G, Tsukamoto H, Howitt G, Pathoulakis C, LaMont T. Clostridium difficile toxin A stimulates enzyme secretin from isolated rat pancreatic acini. Materia Medica Polona 25:127-131, 1993.

44. Kaysen GA, Sun X, Jones H, Martin VI, Joles JA, Tsukamoto H, and Al-Bander H. Non iron mediated alteration in hepatic transferrin gene expression in the nephrotic rats. Kidney Int 47:1068-1077, 1995.

45. Tsukamoto H, Horne W, Kamimura S, Niemelä O, Parkkila S, Ylä-Herttuala, Brittenham GM. Induction of liver cirrhosis in rats fed alcohol and iron. J Clin Invest 96:620-630, 1995.

46. Kamimura S, Tsukamoto H. Cytokine gene expression by Kupffer cells in experimental alcoholic liver fibrosis. Hepatology 21:1304-1309, 1995.

47. Tsukamoto H, Rippe R, Niemela O, Lin M. Roles of oxidative stress in activation of Kupffer and Ito cells in liver fibrogenesis. J Gastroenterol Hepatol 10:50-53, 1995.

48. Tsukamoto H, Cheng S, Blaner W. Effects of dietary polyunsaturated fat on ethanol-induced Ito cell activation. Am J Physiol 270:G581-G586, 1996.

49. Tandler B, Horne W, Brittenham GM, Tsukamoto H. Giant mitochondria induced in pancreatic acinar cells of rats fed ethanol and iron. Anat Rec 245:65-75, 1996

50. Hellerbrand C, Wang SC, Tsukamoto H, Brenner DA, Rippe RA. Expression of intercellular adhesion molecule-1 (ICAM-1) by activated hepatic stellate cells. Hepatology 24:670-676, 1996.

51. Ohata M, Lin M, Satre M, Tsukamoto H. Diminished retinoic acid signaling in hepatic stellate cells in cholestatic liver fibrosis. Am J Physiol 272:G585-G596, 1997.

52. Lin M, Rippe R, Niemelä O, Brittenham GM, Tsukamoto H. Role of iron in NF-kB activation and cytokine gene expression by hepatic macrophages in vitro and in vivo. Am J Physiol 272: G1355-1364, 1997.

53. Horne W, Tandler B, Brittenham GM, Tsukamoto H. Morphological and biochemical characterization of pancreas loaded with iron in portosystemic shunted rats. Exp Mol Pathol in press.

ARTICLES SUBMITTED

1. Ohata M, Tsukamoto H. RAR and RXR expression in normal rat hepatic stellate cells. Hepatology (Submitted).

2. Ohata M, Kamimura S, Pham TV, Lin M, Tsukamoto H. Retinoic acid signaling in rat Kupffer cells. Hepatology (Submitted).

3. Wang SC, Ohata M, Lin M, Tsukamoto H. Expression of IL-10 expression by in vitro and In vivo activated hepatic stellate cells. J Biol Chem (Submitted).

ARTICLES IN PREPARATION

1. Tsukamoto H, Yoshida N, Lin M. Inhibition by anti-TGFb IgG of Ito cell activation and collagen accumulation in experimental biliary liver fibrosis.

NON PEER REVIEW

1. Matsuoka M, Zhang MY, and Tsukamoto H. Activation and Kupffer cell modulation of lipocytes (Ito cells) in alcoholic liver injury. In: K. Kuriyama, T. Takada and H. Ishii, eds. Biomedical and Social Aspects of Alcohol and Alcoholism, Elsevier Science Publishers B.V., Amsterdam, p689-692, 1988.

2. Tsukamoto H, Towner SJ, Xi XP, Otsuki M, and Baba S. A model of ethanol-induced chronic pancreatitis: Pathobiology in cholecystokinin (CCK) regulation of pancreatic acini. In: K. Kuriyama, T. Takada and H. Ishii, eds. Biomedical and Social Aspects of Alcohol and Alcoholism, Elsevier Science Publishers B.V., Amsterdam, p657-661, Kyoto, Japan, 1988.

3. Tsukamoto H, Matsuoka M, Blaner W, Cheng S. Ito cell activation during progression of alcoholic liver fibrosis. In: Wisse E, Knook DL, McCuskey RS, eds. Cells of the Hepatic Sinusoid, Vol 3. Kupffer Cell Foundation, the Netherlands pp. 453-456, 1991.

4. Tsukamoto H. Activation of fat storing cells in alcoholic liver fibrosis: Role of Kupffer cells and lipid peroxidation. In: Surrenti C, Casini A, Milani S, Pinzani M, eds. Falk Symposium No. 71 Fat-Storing Cells in Liver Fibrosis, Kluwer Academic Publishers, London, p189-195, 1994.

5. French SW, Morimoto M, Tsukamoto H. Animal models of alcohol-associated liver injury. In: Hall P, ed. Alcoholic Liver Disease: Pathology and Pathogenesis, 2nd Edition, Australia, p279-296, 1995.

6. Tsukamoto H, Lin M. Ito cell myofibroblastic activation and Kupffer cell cytokine gene expression in alcoholic liver fibrosis. In: Wisse E, Knook DL, Wake K, eds. Cells of the Hepatic Sinusoid, Vol 5. Kupffer Cell Foundation, the Netherlands, pp. 390-391, 1995.

7. Tsukamoto H, Kaplowitz N. Pathogenesis of alcoholic liver disease. In: Kaplowitz N, ed. Liver and Biliary Diseases, 2nd Edition, Williams $ Willkins, Baltimore, pp. 121-138, 1996.

8. Kaplowitz N, Tsukamoto H. Oxidative stress and liver disease. In: Ockner RK, ed. Progress in Liver Disease, In: Boyer JL and Ockner RK, eds. Progress in Liver Disease, volume XIV, WB Saunders Co., Philadelphia, pp. 131-160, 1996.

9. Hill D, Shedlofsky S, McClain C, Diel AM, Tsukamoto H. Cytokines and Liver Disease. In: Remick D, Friedland J, eds. Cytokines in Health and Diseases, 2nd Edition: Cytokines and Liver Disease, Marcel Dekker, Inc. New York, pp. 401-425,1997.

10. Tsukamoto H, Lin M, Pham T-V, Nanji AA, Fong T-L. Role of Inflammation in Liver Fibrogenesis. In: Arroyo V, Bosch J, Rodes J, eds. Thepary in Liver Diseases. The Pathophysiological basis of thepary, Masson, S.A. Barcelona, 1977 (in press).

CURRENT AND PAST RESEARCH FUNDING

1993-2003 NIH/NIAAA Merit Award; R37 AA06603; "Pathogenesis of Progressive Alcoholic Liver Injury"; Principal Investigator; $1,500,000

1996-2001 VA Merit Review Board; "Cellular and Molecular Mechanisms of Ito Cell Activation in Liver Fibrosis; Principal Investigator; $481,200

1995-1998 NIH/NIAAA; R01 DK50217; "Mechanism of Ethanol-induced Pancreatitis"; CO-Principal Investigator (PI: Dr. Steven Pandol); $579,580

1995-2000 NIH; RO1 DK49108; "Oral Chelator Predicated on Desferrithiocin"; Co- Investigator (PI: Dr. Raymond Bergeron); $2,172,765

1993-1996 VA Merit Review Board; "Cellular and Molecular Mechanisms of Ito Cell Activation in Liver Fibrosis"; Principal Investigator; $330,000

1989-1993 NIH/NIAAA; RO1 AA06603-6~10; "Pathogenesis of Progressive Alcoholic Liver Injury"; Principal Investigator; $402,000

1990-1991 NIH/NIDDK; "Regulation of Serum Protein Composition in Nephrosis"; Co-Investigator (PI: Dr. George Kaysen); $132,000

1991-1993 VA Merit Review Board; "Cellular and Molecular Mechanisms of Ito CellActivation in Liver Fibrosis"; Principal Investigator; $163,400

1990-1991 VA Merit Review Board; "Regulation of Albumin Metabolism in Nephrotic Syndrome"; Co-Investigator (PI: Dr. George Kaysen); $100,000

1988-1991 VA Merit Review Board; "Cellular Pathophysiology of Chronic Alcoholic Pancreatitis"; Principal Investigator; $184,000

1985-1988 VA Merit Review Board; "Characterization of Alcohol-Induced Experimental Edematous Pancreatitis"; Principal Investigator; $144,000

1984-1987 VA Merit Review Board; "Role of Active Pancreatic Protease in Acute Pancreatitis"; Co-Investigator (PI: Dr. Corey Largman); $267,600

1986-1989 NIH/NIAAA; RO1 AA06603-03~05; "Pathogenesis of Progressive Alcoholic Liver Injury"; Principal Investigator; $328,000

1984-1986 NIH/NIAAA; RO1 AA06603-01~02; "A New Rat Model of Chronic Alcohol Intoxication"; Principal Investigator; $153,000

TEACHING RECORD

University of Southern California (1994-present):

A. Graduate Student Teaching

Pathology #570, Seminars in Pathology, one hour lecture on Cell Biology of Liver Fibrosis plus 2.5 hr graduate student paper review.

Pathology #599, Special Topic (Frontiers in Basic and Applied Sciences), Co-course leader, 1.5 units per semester, two semesters per year, 1997-

B. Conferences

Program director for USC Liver Disease Research Center Seminar, one hour seminar per week for 10 months a year. 1994-1997

Journal Club for Gastroenterology and Hepatology fellows, preceptor and presenter participation, 1 1/2 hours per week for 10 months a year. 1994-

C. Fellow Laboratory Training

Elimelech Zuckerman, M.D., June 1995, January-May 1996 - Dr. Zuckerman, a Liver fellow, was trained for isolation of Kupffer cells, extraction of total RNA, and Northern blot hybridization analysis to examine mRNA expression of gGCS, gGT, and a canaricular GSH transporter in Kupffer cells..

Thai-Van Pham, M.D., December 1995 and January 1996 - Dr. Pham was trained for Kupffer cell isolation, nuclear protein extraction and electrophoretic mobility shift assay to examine the role of retinic acid signaling in modulation of cytokine gene expression by rat Kupffer cells.

S Cecilia Wang, Ph.D., 1995-present - As a post-doctral fellow, she is assigned to a study examining expression of chemokines and adhesion molecules by activated hepatic stellate cells in vitro and vivo.

Mitsuru Ohata, M.D., Ph.D., 1994 - present - Dr. Ohata examined the molecular consequence of diminished retinoic acid signaling in activation of hepatic stellate cells in cholestatic liver fibrosis.

D. Graduate Student Research Supervised

Mariana Keshmeshian, a PhD student in Molecular Pathology, 1996-

Z Austin Dai, a PhD student in Molecular Pathology, 1996-

Case Western Reserve University Teaching Activity (1991-1994):

A. Student Teaching

Lectures on cell and molecular biology of liver fibrogenesis for first year medical students

B. Conferences

Co-program director for a city wide basic science program for gastroenterology fellows entitled, "Frontiers in Gastroenterology and Hepatology". One and half credit hours per lecture, two lectures per month for 9 months a year.

Organizer for biweekly research conferences on "Current Status on Liver Research" for gastroenterology fellows at MetroHealth Medical Center.

C. Graduate Students Supervised

Donald Keenen, a MD. Ph.D student in surgical research, "Immunomodulation in ischemia-reprefusion organ injury: role of lipid peroxidation aldehydic products", 1991-1994.

Sandy Yeager, a MS student in nutrition, "Role of supplemental iron in alcoholic liver injury", 1992-1994.

D. Resident/Fellow Laboratory Training

Medical Residents Supervised (These residents took research electives during their second year)

Roy Soetikno, M.D. August, November 1992 - Dr. Soetikno studied effects of angiotensin II on exocrine pancreas using an ex vivo perfused pancreas model.

Martha Rachedi, M.D. September, October 1992 - Dr. Rachedi examined TGFb1 gene expression in fibrotic livers of rat given ethanol and iron by performing Northern blot analysis.

Rakesh Singal, M.D. January, February 1993 - Dr. Singal examined effects of 4-hydroxynonenal and malondialdehyde on rat monocyte and Kupffer cell chemotaxis and chemokinetic.

GI Fellow Supervised

LeChu Su, M.D., Ph.D. 1992-1993 - Dr. Su spent her third year of GI fellowship program to examine expression of retinoic acid receptors and retinoid X receptors by Ito cells during activation in vivo and in vitro.

UC Davis/Martinez VAMC Teaching Activity 1989-1991

A. Student Teaching

Co-course leader for a post-graduate course, # Gastro 290, Frontiers in Basic Gastrointestinal and Liver Research for medical students, residents, fellows, and graduate students. One and half academic units per quarter. Three quarters a year. One lecture each month.

B. Conferences

Weekly GI Fellow Journal Club

C. Resident/Fellow Laboratory Training

Resident Supervised

Jeffrey H. Lee, M.D. April, May, 1991 - Dr. Lee was trained to examine expression of procollagen a1(I) gene in livers of experimental alcoholic liver fibrosis.

GI Fellows Supervised

Mohamed Vadva, M.D. 1990 - Dr. Vadva spent six months of his second fellow year in my laboratory to examine effects of angiotensin II antagonists on exocrine pancreatic function in rats.

Tirso Castillo, M.D. 1991 - Dr. Castillo worked in the laboratory during the second year of his fellowship training to investigate the role of P4502E1 in microsomal lipid peroxidation in experimental alcoholic liver disease.

Teaching Philosophy

As a basic scientist faculty, my goal for teaching in medical schools has always been to promote better understanding by medical students, residents, and fellows of a bridge between new progresses in basic science and development of foundation for future medicine. My teaching involves bringing most current research information on biology and pathobiology of the liver into a class or conference room to incite discussions on how it has had or will have direct impact on diagnosis and treatment of gastrointestinal and liver diseases. This teaching concept has underlied the development of two postgraduate courses at UC Davis and Case Western Reserve University. In both courses (one with university academic credit and another with CME credit), the participants were systematically exposed to topics which epitomized evolution of modern gastroenterology and hepatology based upon new scientific technology and findings.