US-Asian Pacific Rim Collaborations

Transcription

1 research center for alcoholic liver and pancreatic diseases cirrhosis research program The Center is supported by grants from the National Institute on Alcohol Abuse and Alcoholism, P50 AA11999, T32 AA07578 & R24AA12885 Winter 2005 A publication of the Research Center for Alcoholic Liver and Pancreatic Diseases Inside this Issue US-Asian Pacific Rim Collaborations Center Networks with Local Community Leaders for Community Seminar in March 2006 Spotlight on Kasper Wang 2005 Lee Summer Student Fellowship Awards Training Grant Renewed Recent Publications by Center Members New Grants by Center Members International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis CONTACTS: Hide Tsukamoto, Director htsukamo@usc.edu Anne Taguchi, Administrator ataguchi@usc.edu Fax: Web: US-Asian Pacific Rim Collaborations By Hide Tsukamoto NIAAA is beginning to develop a Pacific Rim Alcohol Research Consortium that would include investigators from the U.S., China, Japan, and Australia and others who are interested. Alcohol-related problems are global and are increasing in developed and developing Asian countries. Therefore, this concept of international consortium is particularly timely and important in facilitating a global approach to our common interest in research, prevention, treatment of alcohol-related health problems. As part of implementation of this concept, NIAAA has signed a formal Letter of Intent (LOI) on research collaboration with the Institute for Nutritional Sciences (INS) of the Chinese Academy of Sciences (CAS) in Shanghai, China and renewed its LOI with the National Hospital Organization, Kurihama Alcoholism Center in Kurihama, Japan. As a first critical step to promote collaborations between US and China, NIAAA and INS of CAS jointly sponsored a workshop entitled Healthy People 2020 Alcohol, Obesity and Diabetes in Shanghai, October 12-14, The meeting was attended by the members of NIAAA, NIDDK, INS, and other Center Networks with Local Community Leaders for Community Seminar in March 2006 By Anne Taguchi Continued on page 5 The Center is pleased to announce its third annual community seminar on Alcohol and Your Health scheduled for March 3, Panelists will include physicians and researchers from USC, UCLA, Loma Linda and Berkeley. Jerry Reilly, CEO of Organs for Life Foundation, and liver transplant recipient, will again be hosting the event. The format will be in a talk show style, with participation from the audience after a brief introduction on the liver and pancreas. With the novel concept that alcohol related disease is a life-style disease much like diabetes, hypertension, coronary heart disease and stroke, and because of the prevalence of these diseases in the Los Angeles County area, we have started establishing relationships with and have pursued networking activities with local community leaders, healthcare providers and social workers to help bring awareness to the local lay public. To this end, the Center is establishing networking opportunities with the help of various groups such as the National Asian Pacific American Families Against Substance Abuse (NAPAFASA), Los Angeles County s Alcohol and Drug Program Administration, the Korean Health, Education, Information and Re- Continued on page 5

2 page 2 Spotlight on By Vijay Kalra Kasper Wang Kasper Wang is a pediatric surgeon at Childrens Hospital Los Angeles (CHLA) and an Assistant Professor of Surgery at USC Keck School of Medicine, and an active Member of the Research Center for Alcoholic Liver and Pancreatic Diseases. Kasper, who was born in Lincoln, Nebraska, completed high school at Lake Mary High School in Florida. For his outstanding talent, he was awarded STAR National Student Scholarship from the General Electric Company. During his undergraduate studies at the Johns Hopkins University, he worked at the medical school where he developed a passion for research studying intracellular protein trafficking in hepatocytes with Dr. Ann L. Hubbard. He entered medical school in 1989 at the Johns Hopkins University School of Medicine and after his first year of medical school, he received a summer research fellowship award to study dopamine receptor restriction fragment length polymorphisms in substance abusers at the National Institute of Drug Abuse. Later, he joined the laboratory of Dr. Mark Clemens to study gap junctional communication in the liver during sepsis. After completing medical school, Kasper moved to Stanford University, where he completed internship and residency in general surgery. For three years in the middle of his surgery residency, he studied aquaporin water channels in the gastrointestinal tract under the guidance of Professor Alan Verkman. They developed aquaporin knockout mice and showed that transgenic mice lacking aquaporin-1 water channels had defective fat processing in part from pancreatic exocrine insufficiency. In 2002, Kasper moved to CHLA for specialized training in pediatric surgery and took on a faculty position here at USC in As faculty, Kasper initiated a research program studying liver organogenesis and regeneration. Dr. Wang and his team are studying the role of fibroblast growth factor 10 in the pathogenesis of liver and biliary tract development. Additionally, Kasper is elucidating the FGF-10 induced signaling in liver to understand the process of liver morphogenesis Continued on page Lee Summer Student Fellowship Awards By Anne Taguchi Now in its fifth year, the Center once again had a wonderful group of students participate in the Lee Summer Student Fellowship program. This program promotes the involvement of undergraduate and Master s students in research on our Center s theme. The program is named after Dr. S.P. Lee who made a donation toward this noble cause. In collaboration with the Edmondson Summer Fellowship Program sponsored by the Department of Pathology at USC, the Lee Summer Students participated in their laboratory safety classes and some of their lectures. The Lee program entails a minimum of 8 weeks of research during the summer in the Center investigator s laboratory and a required presentation on his/her research at the Center s Progress Report Meeting which was held on August 16, Kasper Wang and Shigang Xiong with Travis Chong; Steve Pandol and Ilya Gukovsky with Mark Awad; Hide Tsukamoto with Jason Cheng; Henry Lin with Justin Barad; Anna Gukovskaya with Mathew Zebrowski Five students presented their summer work at this meeting. Mark Awad, an undergraduate student at USC, was recruited from the Edmonson Summer Fellowship Program student base. He worked with Dr. Steve Pandol on a project entitled, Characterization of pancreatic gene expression in the combined cyclosporine and cerulean model of chronic alcoholic pancreatitis. Travis Chong, undergraduate student in Biomedical Engineering at USC worked with Continued on page 3

3 page 3 Kasper Wang, Continued from page 2 and development of end stage alcoholic liver disease. To support his investigations, Dr. Wang recently obtained funding for a pilot grant from the Alcoholic Liver and Pancreatic Disease Center at USC Keck School of Medicine as well as a Research Career Development Award from the Saban Research Institute at CHLA. Kasper is married to his wife, Lourdes, of 13 years. They have two children, Bryan, 9, and Emily, 3. What little time he has outside of the hospital Kasper spends with his family or on hobbies including swimming, running, and coaching his son s travel baseball team. Kasper Wangs s basic hypothesis model depicting the role of FGF-10 in cross talk between hepatic stellate cells and hepatic progenitor cells in liver development and regeneration, as well as ethanols inhibitory action. Training Grant Renewed for Another Five Years By Anne Taguchi We are pleased to announce that the NIAAA-funded Training Program in Alcoholic Liver and Pancreatic Diseases (ALPD) was renewed for another 5 year cycle! The main objective of our training program is to support the development of independent research career of young scientists in the pathogenesis of ALPD and cirrhosis. We are particularly interested in training and promoting specialization in cutting-edge and cell-type specific research aimed at molecular elucidation of alcohol-induced sensitization and priming mechanisms for the genesis of ALPD. Our program will support funding for 4 postdoctoral and 1 predoctoral fellows a year. Each trainee will commit to two years of training. In addition to laboratory training, trainees will have the opportunity to participate in didactic courses, our annual symposium and progress report meetings, single-topic workshops, and two weeks in the laboratories of Center members or Training Faculty other than their primary mentor. These sessions allow the trainee to become familiar with experimental approaches and techniques different but complementary to those of the mentor's laboratory. We are currently inviting applications for trainee positions under our training grant under the mentorship of well established investigators. Candidates should have a Ph.D. in biological sciences, good communication skills and ability to conduct independent research, and have no more than seven years of post-doctoral research experience. The training environment is highly conducive to promote independent research and grant writing. The NIH post-doctoral training grant requirements are that the individual should have US permanent residency or citizenship and salary commensurate with experience. Please CV, a statement of interests and names of three references to Vijay Kalra, Ph.D. (vkalra@usc.edu) Lee Summer Students, Continued from page 2 Dr. Shigang Xiong and Pilot Project PI, Dr. Kasper Wang on a project entitled The role of Fgf10 in liver regeneration. Jason Cheng, graduate student in the Department of Pathology at USC worked with Dr. Hide Tsukamoto on a project entitled The role of beta-catenin in activation of Hepatic Stellate Cells. Justin Barad, an undergraduate student at UC Berkeley, worked with Dr. Henry Lin on a project entitled A mouse model of small intestinal bacterial overgrowth. Mathew Zebrowski, mentored by Dr. Anna Gukovskaya, and an undergraduate student at Long Beach State University, worked on a project entitled, Effects of ethanol on the regulation of death mediators in experimental acute pancreatitis. Each student that presented received a certificate and an $800 check upon completion of their fellowship. All in attendance at the presentations were very impressed with the student s work and with the quality of their presentations. We hope that the students summer work was an enjoyable one, and we look forward to seeing some of these students as future scientists. Congratulations to all!

4 page 4 Most Recent Publications by Center Members Fernandez-Checa JC, Kaplowitz N. Hepatic mitochondrial glutathione: transport and role in disease and toxicity. Toxicol Appl Pharmacol May 1;204(3): Review. Ji C, Mehrian-Shai R, Chan C, Hsu YH, Kaplowitz N. Role of CHOP in hepatic apoptosis in the murine model of intragastric ethanol feeding. Alcohol Clin Exp Res Aug;29(8): Sailors JL, French SW. The unique simultaneous occurrence of granular cell tumor, gastrointestinal stromal tumor, and gastric adenocarcinoma. Arch Pathol Lab Med May;129(5):e Nan L, Wu Y, Bardag-Gorce F, Li J, French BA, Wilson LT, French SW. The p105/50 NF-kappaB pathway is essential for Mallory body formation. Exp Mol Pathol Jun;78(3): Bardag-Gorce F, Wilson L, Nan L, Li J, French BA, Morgan TR, Morgan K, French SW. CYP2E1 inhibition enhances mallory body formation. Exp Mol Pathol Jun;78(3): Li J, French BA, Nan L, Fu P, French SW. Uncoupling of oxidative phosphorylation prevents the urinary alcohol level cycling caused by feeding ethanol continuously at a constant rate. Exp Mol Pathol Jun;78(3): Esfandiari F, Villanueva JA, Wong DH, French SW, Halsted CH. Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs. Am J Physiol Gastrointest Liver Physiol Jul;289(1):G Wu Y, Nan L, Bardag-Gorce F, Li J, French BA, Wilson LT, Dedes J, French SW. The role of laminin-integrin signaling in triggering MB formation. An in vivo and in vitro study. Exp Mol Pathol Aug;79(1):1-8. Bardag-Gorce F, Francis T, Nan L, Li J, He Lue Y, French BA, French SW. Modifications in P62 occur due to proteasome inhibition in alcoholic liver disease. Life Sci Sep 30;77(20): French BA, Dedes J, Bardag-Gorce F, Li J, Wilson L, Fu P, Nan L, French SW. Microarray analysis of gene expression in the liver during the urinary ethanol cycle in rats fed ethanol intragastrically at a constant rate. Exp Mol Pathol Oct;79(2): Nguyen T, Tang W, Nan L, Deleon M, French SW. The role of bile duct reactive change in the pathogenesis of liver fibrosis due to hepatitis C. Exp Mol Pathol Oct;79(2):95-9. She H, Xiong S, Hazra S, Tsukamoto H. Adipogenic transcriptional regulation of hepatic stellate cells. J Biol Chem Feb 11;280(6): Yang MD, Deng QG, Chen S, Xiong S, Koop D, Tsukamoto H. Hepatoprotective mechanisms of Yan-gan-wan. Hepatol Res : Deng QG, She H, Cheng JH, French SW, Koop DR, Xiong S, Tsukamoto H. Steatohepatitis induced by intragastric overfeeding in mice. Hepatology Oct;42(4): Yavrom S, Chen L, Xiong S, Wang J, Rippe RA, Tsukamoto H. PPARgamma suppresses proximal alpha 1(I) collagen promoter via inhibition of p300-facilitated NF-I binding to DNA in hepatic stellate cells. J Biol Chem Dec 9;280(49): Pandol SJ. Acute pancreatitis. Curr Opin Gastroenterol Sep;21(5): Apte MV, Zima T, Dooley S, Siegmund SV, Pandol SJ, Singer MV. Signal transduction in alcohol-related diseases. Alcohol Clin Exp Res Jul;29(7): Satoh A, Gukovskaya AS, Edderkaoui M, Daghighian MS, Reeve JR Jr, Shimosegawa T, Pandol SJ. Tumor necrosis factor-alpha mediates pancreatitis responses in acinar cells via protein kinase C and proline-rich tyrosine kinase 2. Gastroenterology Aug;129(2): Go VL, Gukovskaya A, Pandol SJ. Alcohol and pancreatic cancer. Alcohol Apr;35(3): Pandol SJ. Are we studying the correct state of the stellate cell to elucidate mechanisms of chronic pancreatitis? Gut Jun;54(6): Edderkaoui M, Hong P, Vaquero EC, Lee JK, Fischer L, Friess H, Buchler MW, Lerch MM, Pandol SJ, Gukovskaya AS. Extracellular matrix stimulates reactive oxygen species production and increases pancreatic cancer cell survival through 5-lipoxygenase and NADPH oxidase. Am J Physiol Gastrointest Liver Physiol Dec;289(6):G Mato JM, Lu SC. Homocysteine, the bad thiol. Hepatology May;41(5): Minagawa M, Kawamura H, Liu Z, Govindarajan S, Dennert G. Suppression of adenoviral gene expression in the liver: role of innate vs adaptive immunity and their cell lysis mechanisms. Liver Int Jun;25(3): Yang H, Magilnick N, Lee C, Kalmaz D, Ou X, Chan JY, Lu SC. Nrf1 and Nrf2 regulate rat glutamate-cysteine ligase catalytic subunit transcription indirectly via NF-kappaB and AP-1. Mol Cell Biol Jul;25(14): Lee TD, Yang H, Whang J, Lu SC. Cloning and characterization of the human glutathione synthetase 5'-flanking region. Biochem J Sep 1;390(Pt 2): Yang H, Magilnick N, Ou X, Lu SC. Tumour necrosis factor alpha induces co-ordinated activation of rat GSH synthetic enzymes via nuclear factor kappab and activator protein-1. Biochem J Oct 15;391(Pt 2): Chang ML, Chen HL, Lu SC. Possible Role of Triacylglycerol-Rich Lipoproteins in the Down-Regulation of Adipose Obese mrna Expression in Rats Re-Fed a High-Fat Diet. J Biomed Sci. 2005;12(4):621-8.

5 page 5 Community Seminar, Continued from page 3 3rd Annual Community Seminar Alcohol and Your Health Friday, March 3, AM - Noon The Alhambra - Auditorium 1000 South Fremont Avenue, Alhambra CA FREE!! LECTURE AND OPEN FORUM Q&A SESSION WITH USC, UCLA, LOMA LINDA & BERKELEY DOCTORS! More information is available at Or contact: Phone: jjorozco@usc.edu search group, the Pacific Islander Health Partnership, the Latino Health Access, local area Neighborhood Councils, the American Liver Foundation, Greater Los Angeles Chapter, New Direction at the West Los Angeles VA Medical Center and the. These groups with their associated community leaders will be able to target audience members at a grass roots level in order to have the most meaningful participation and to have the audience benefit as much as possible from the seminar. This seminar will give the public a chance to meet and talk to the panelists who are involved in the research and treatment of liver and pancreas diseases. Frequently asked questions concerning intake of alcohol, viral hepatitis, diet, obesity transplantation etc. will be discussed in a very informal and interactive format. For more information, please visit our website at. US-Asian Collaborations, Continued from page 1 scientists from both countries. David Guidot from Emory University and I were also invited to participate as NIAAA Alcohol Research Center directors. We witnessed serious conceptual and financial commitments by CAS and INS toward cutting-edge research and prevention for alcohol, obesity, and diabetes, that singly and more importantly in combination, contribute to an emerging thereat of costly life style diseases in China. The INS has established the first Alcohol Research Center and we were given a tour of the center and INS. Division heads for different disciplines at INS were mostly, if not all, trained in the US for many years and many have held and some continue to hold highly productive academic positions at major institutions in the U.S. This rapid and inspiring move of CAS epitomizes what China as a whole is currently experiencing and also serves as an impetus for other countries to develop similar global and integrative approaches for life-style diseases to which alcohol makes a pivotal contribution. As a NIAAA-funded research center on the campus of USC that is historically known for its active involvement in international relations particularly in a Pacific Rim region, we wish to take a major role in the proposed consortium. To this end, the international symposium that we are sponsoring next May, should serve as an ideal opportunity to stimulate specific discussions for international collaborations. Among the 18 international speakers and guests who are invited to the symposium, several represent Shanghai s INS and its alcohol research center. Japanese Society of Gastroenterology is also sending their delegates to the event including its Director General and past Director General. There will also be scheduled presentations by NIAAA staff at the symposium on mechanisms of federal support on international collaborations. Specific areas of collaborations with Chinese or Japanese investigators that may prove to be fruitful include epidemiology and gene-environment interactions for alcoholic liver and pancreatic diseases, clinical studies including trials, genetic, proteomic, and metabolomic profiling. If you are interested in more information on US- Asian collaborations, please feel free to contact my office at (323) or. New Grants by Center Members Kaplowitz, Neil, R01 DK , Role of Glutathione Redox Status in Hepataotoxicity Lu, Shelly, R01 DK pending (priority score 121) Regulation of Methionine Adenosyltransferase in Liver Tsukamoto, Hidekazu, R24 AA pending (priority score 137), Nonparenchymal Liver Cell Core Pandol, Stephen, R21 AA pending (priority score 140), Alcohol and the Exocrine Pancreas ER Stress Responses Lugea, Aurelia, R21 AA A1 pending (priority score 141) Plasminogen System and Alcoholic Pancreatitis

6 page 6 International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis May 18 & 19, 2006, Los Angeles, California Preceding 2006 Digestive Diseases Week in Los Angeles Venue - The Ritz-Carlton, Marina Del Rey This symposium will assemble eighteen international and twelve U.S. speakers and guests along with leading investigators from the NIAAA funded Research Center for Alcoholic Liver and Pancreatic Diseases. It will provide an exciting forum to discuss and exchange cutting-edge science on the following major themes as they relate to the pathogenesis and pathophysiology of alcoholic liver and pancreatic diseases and cirrhosis: cell death and survival; oxidant stress and inflammation; metabolism and cancer; and stellate cell biology. Pre-registration by March 1 is required and number of attendees limited to 120. Please register via our website at. 30 travel awards are offered to graduate students, potdocs, or junior scientists whose abstracts for posters are considered to be excellent. Further information: Please visit our website for further details, registration information, travel award details, venue details, poster abstract submission information, and to register online. Or contact Anne Taguchi , ataguchi@usc.edu Sponsored By: The Research Center for Alcoholic Liver and Pancreatic Diseases National Institute on Alcohol Abuse and Alcoholism Co-Sponsored By: Japanese Society of Gastroenterology Institute for Nutritional Sciences, Chinese Academy of Sciences American Liver Foundation, Greater Los Angeles Chapter Research Center for Alcoholic Liver and Pancreatic Diseases Keck School of Medicine of the 1333 San Pablo Street, MMR 4 th Floor Los Angeles, CA 90033