1995 BIOLOGY AND DIAGNOSIS PROGRAM AREA EXCHANGE SCIENTIST REPORTS

SUMMARY REPORTS OF EXCHANGE SCIENTISTS

(1) Takashi Suda
Osaka Bioscience Institute, Research Scientist

SPONSOR AND HOST INSTITUTION:
Dr. Albert Zlotnik, DNAX Research Institute
DATES OF VISIT: July 16-30, 1995

SUMMARY OF ACTIVITIES:
July 17, I visited Dr. Francis V. Chisari (The Scripps Research Institute, La Jolla, CA). I have been engaged in a collaborative work concerning “involvement of Fas and Fas ligand in CTL induced hepatitis” with Dr. Chisari’s group. We exchanged our current results and discussed about future experiments. July 19, I visited Dr. Philip L. Cohen (University of North Carolina, Chapel Hill, NC), who is an authority of the study regarding 1pr mouse. It was demonstrated in our laboratory that mouse 1pr mutation is a loss-of-function mutation of the Fas gene. Since 1pr is a leaky mutation, we have produced mice carrying disrupted Fas gene (Fas KO mice). I gave a seminar about our study of Fas KO mice. I got valuable comments from Dr. Cohen. Dr. Cohen told me about their recent study regarding B cell-abnormalities in 1pr mice, and one regarding mice carrying both an exogenous bc1-2 gene and the homozygous 1pr mutation. I had a chance to talk to other researchers. Dr. Steve Clarke (University of North Carolina, Chapel Hill, NC) told me about his detailed study regarding somatic mutation and affinity maturation of anti-DNA and anti-Sm autoantibodies in 1pr mice. Dr. Cliff Tepper (Duke University) told me about his study regarding involvement of ceramide in a signal transduction pathway of Fas. Dr. Minoru Satoh and Dr. Ajay Ajimani told me about their study demonstrating that the expression of Ku antigen was down-regulated in apoptotic cells. July 21, I visited Dr. Christopher Goodnow (Howard Hughes Medical Institute, Stanford Medical School, Stanford, CA). I told him about our study regarding Fas-KO mice. Dr. Goodnow told me about their very recent study regarding a role of Fas in B cell tolerance using anti-HEL immunoglobulin and HEL gene double transgenic mice carrying the 1pr mutation. July 24 to July 29, I visited Dr. Albert Zlotnik (DNAX Research Institute, Palo Alto, CA). I told him about current progress of our study regarding Fas and Fas ligand. He told me about their study regarding lymphotactin and CRTAg which were recently cloned in his laboratory. Dr. Zlotnik and his colleagues have been successfully isolated new genes from subtraction cDNA library derived from thymic pre-T cells. Thus, I learned their subtraction techniques and screening procedures.

(2) Yasuhiro Minami
Department of Biochemistry, Kobe University School of Medicine

SPONSOR AND HOST INSTITUTION:
Dr. Richard D. Klausner, National Cancer Institute, Director
1) National Cancer Institute, National Institutes of Health 5 days
Dr. Richard D. Klausner, Dr. John J. O’Shea and
Dr. Lawrence E. Samelson
2) Northwestern University 3 days
Dr. Richard I. Morimoto
3) Harvard University 3 days
Dr. Victor Hsu
DATES OF VISIT: September 20-October 1, 1995

SUMMARY OF ACTIVITIES:
The purposes of my visit in this scientist exchange program was to have extensive scientific interactions with many outstanding scientists in US and to discuss about possible future collaborative studies. In fact, I could get valuable advice and information quite useful for my ongoing projects from the scientists with whom I had interviews. In addition, I was also very much encouraged by Dr. Richard D. Klausner (Director, NCI) who is my mentor. I also gave my talk at NCI (sponsored by Dr. John J. O’Shea), Northwestern University (by Dr. Richard I. Morimoto) and Harvard University (by Dr. Victor Hsu). The titles of my seminars were “Immuno-hematopoietic cell signaling: Roles of multiple protein tyrosine kinases” and “Current view of IL-2 receptor mediated signal transduction,” respectively. Through the mutual scientific interactions with the leading scientists, I could obtain many up-to-date information. I will describe the brief summary of these interactions below. At NIH, I had interviews with Drs. Lawrence E. Samelson (he was my previous supervisor), Juan Bonifacino et al. Drs. Samelson and Bonifacino talked about the roles of cbl oncogene product in T cell signaling and the molecules involved in trafficking between TGN and plasma membrane, respectively. At NCI, Drs. John J. O’Shea, Allan Weiss man and John Ashley told me about their current studies on IL-2/IL-4 signaling, protein modification (including ubiquitinylation), and on regulation of apoptosis in lymphocytes, respectively. I had also extensively discussed with Dr. O’Shea about our possible collaborative studies in addition to our on-going studies. At Northwestern University Dr. Morimoto talked about their current studies on the regulation of heat shock proteins as well as heat shock factors. I had also had interviews with the scientists who are extensively working on the Drosophila genetics (Drs. Bob Holmgren, Teresa Orenic, Amy Bejsovec). These interviews are of great help for me, since we have just started to work on Drosophila system to elucidate the roles of protein kinases in Drosophila development. Finally, at Harvard University I could also have fruitful scientific interactions with m2lny scientists, including Drs. Victor Hsu, Michael Brenner, Hamid Band and Craig Morita. From Dr. Hsu I could learn a lot about current studies on ARFs. With Dr. Band I discussed our studies on lymphocyte signaling. In summary, I am convinced that I could have fruitful scientific interactions and exchange ideas as well as reagents through this scientist exchange program.

(3) Eiichi Nakayama
Department of Parasitology and Immunology, Okayama University Medical School

SPONSOR AND HOST INSTITUTION:
Dr. Lloyd J. Old, Ludwig Institute for Cancer Research, New York Unit at Memorial Sloan-Kettering Cancer Center
DATES OF VISIT: October 14-22, 1995

SUMMARY OF ACTIVITIES:
The Ludwig Institute for Cahcer Research of which Dr. Old is director, is unique and has 10 branches in major cities around the world. The first objective of my visit there was to learn about the progress of research in tumor immunology at the Ludwig Institute especially on tumor antigens recognized by T cells Dr Old is also Director of the Cancer Research Institute (CRI) which is an organization supporting research in tumor immunology. The second objective was to learn about the future directions of cancer immunology from the activities at CRI. The third objective was to discuss various matters with fellow researchers at the New York Unit of the Ludwig Institute and the Sloan-Kettering Institute. From my visit, I realized that a substantial number of tumor rejection antigens have already been found and the research is already at the stage of application to clinical use. Tumor rejection antigens recognized by cytotoxic T lymphocytes so far identified are mainly from malignant melanoma. However, in renal cancer, several new genes coding for antigenic peptides seem to have been identified. On the other hand, tyrosinase peptides have been shown to evoke immune responses in melanoma patients. Based on our experiences with murine tumor systems, we plan to study human tumor antigens. Therefore, to know about the new findings and ongoing research in this field is most helpful to us. CRI started symposia entitled Cancer Vaccine and Monoclonal Antibody to Cancer which are held alternatively each year. The symposia cover most of the progress in tumor immunology research. My laboratory is interested in searching for tumor rejection antigens recognized by cytotoxic T-lymphocytes and inducing effective immune responses against cancers using those antigens During my visit, I learned that to augment the weak antigenicity of tumor antigen, a variety of approaches are taken. Dr. P. Livingston at Sloan-Kettering has tried different types of adjuvants and found that a new type of adjuvant QS-21 has remarkable activity. Another approach to enhance tumor immune response is via the use of cytokines. Even a small dose of IL-12 appears to cause resistance to tumors in experimental murine systems. The discussions and the information acquired during this visit will be very helpful to future work in my laboratory.