1989 BIOLOGY AND DIAGNOSIS PROGRAM AREA EXCHANGE SCIENTIST REPORTS

SUMMARY REPORTS OF EXCHANGE SCIENTISTS

(1) Tadashi Utakoji
Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan

Sponsors and Host Institutions:
Drs. Anthony Carrano and James Tucker
Lawrence Livermore National Laboratory
Biomedical Sciences Division, Livermore California
Dr. Berton Zbar
Frederick Cancer Research Facility
Laboratory of Immunobiology
Frederick. Maryland
Dr. Patrick H. O’Farrell
Universlty of California at San Francisco
Department of Biochemistry and Biophysics.
Dr. Sheldon Wolff University of California at San Francisco
Department of Radiobiology and Environmental Health.
Date of visit:
February 26 - March 2
Lawrence Livermore
National Laboratory Human Genome
March 5 - 9
NCI-Frederick Cancer Research Facility
March 12 - 16
University of California at San Francisco

Summary of Activities:
a) In Human Genome Center, I observed and inspected all the activities of genome analysis of human chromosome No. 19 including computer facilities for this project. Most impressive thing to me was the extensive computerization in every step of procedures and in the storage of the results obtained through individual action. It appeared to me the important thing for such a big project is to provide access and facilities so that every participants can approach the entire archives. The other one I was impressed was the beautiful chromosome figure observed by the “chromosome painting”. This technique, when propagated to many cytogenetics laboratories, will surely become indispensable in the study of translocations and numerical aberrations which are often found in cancer cells. As an informal seminar, I had a talk on reduced rates of sister chromatid exchange in low-oxygen culture of human peripheral blood lymphocytes using 5 slides.
b) In NCI-FCRF, Dr. Zbar was studying the oncogene/ anti-oncogene for human renal cell carcinomas. The DNAs from the patients and their families of von Hipple-Lindau disease, that is known to associate with renal carcinomas often, was analyzed for the informative cases with regard to the specific DNA probe for restriction fragment length polymorphism. This particular hereditary disease is a rare one, and to find a case with parents of heteromorphic for the DNA probe employed is further rarer. Methods of DNA analysis was not particular. The approach seemed to be entirely different from the one in Human Genome Center, Lawrence Livermore National Laboratory. Because of reasons above described, the progress appeared to be slow but surely steady. It was highly interesting to think of two wholly different approach for the human genome analysis.
c) In the Department of Biochemistry and Biophysics, Dr. O’Farrell has been studying the structure and function of the cell cycle regulating gene(s) of Drosophila. Homologous genes and/or their products have been known recently in yeast and in human cells, and have been interested for their cell cycle controlling or mitosis-regulating functions. In this Laboratory, for the first time I could see and watch a young scientist manipulating Drosophila embryos for his molecular biological and morphological studies of whole-mount specimen. I have been always admiring the beautiful microscopic pictures accompanied to Dr. O’Farrell’s and his colleagues' publications on Drosophila subjects. Now I could peer the secret of their excellent pictures. Disclosed function of the gene, “string”, is a part of biochemical clock of Drosophila embryogenesis. It is clarified that the regulation of timing in Drosophila embryogenesis is not depending on “cyclin” but on the product of “string”. Such studies on the structure and functions of cell cycle- and mitosis-regulating clock gene(s) will become important subjects in understanding of the mechanisms of numerical aberrations of chromosomes which are frequently observed in cancer cells. In Dr. Wolff’s Laboratory where active studies on sister chromatid exchanges, DNA damage and its repair, Xeroderma pigmentosum, and Ataxia telangiectasia had been performed. I found that rather cell biological studies of extracellular matrix including the embryonic stem (ES) cell culture are going on. Dr. James E. Cleaver told me that in normal human and Xeroderma pigmentosum cells the removal of UV-irradiation product in DNA, cyclobutane dimer, may not be essential to the survival of these cells which is rather different aspect from the previously believed.
Visiting three independent Institutions, widely related but individually different, and talking with young, active scientists was highly stimulative to me. I gratefully appreciate for this valuable opportunity.

(2) Hideo Yagita
Juntendo University School of Medicine

Sponsor and Host Institution:
Dr. Ellis L. Reinherz
Chief, Department of Immunobiology
Dana-Farber Cancer Institute
Dates of Visit: February 18 - March 9, 1990

Summary of Activities:
1) I attended the annual meeting of US-Japan Cooperative Cancer Research Program (Feb. 19- 20) and presented our recent data regarding murine lymphocyte adhesion molecules. In this meeting, I discussed with Drs. Paul Kincade (Oklahoma Medical Research Foundation). Ada Kruisbeek (NIH), Jeff Bluestone (University of Chicago), and Stephen Shaw (NIH). Several collaborative research projects were planned through such discussions.
2) I visited Frederick Cancer Research Facility at Feb. 22 and discussed with Drs. John Ortaldo and Howard Young (Laboratory of Experimental Immunology) on the mechanisms of the NK and T-cell mediated cytolysis. We made plans of collaborative researches on the PFP (pore-forming protein) expression in these cells and the putative murine NK cell receptor.
3) I visited New York University Medical Center at Feb. 23 and gave a seminar titled “CD2, LFA-1 and other adhesion molecules involved in murine lymphocyte interactions”. l discussed with Dr. Jeanette Thorbecke (Department of Pathology) on this matter.
4) I visited Dana Farber Cancer Institute at Feb. 26-27 and gave a seminar titled "CD2, LFA-1 and other adhesion molecules involved in murine lymphocyte interactions". I discussed with Drs. Ellis Reinherz (Department of Immunobiology) and Steven Burakoff (Department of Pediatric Oncology), and made plans of collaborative researches with them on the function of murine CD2.
5) I visited Washington University School of Medicine at Feb. 28 - Mar. I and gave a seminar titled “CD2, LFA-1 and other adhesion molecules involved in murine lymphocyte differentiation”. I discussed with Dr. Dennis Loh (Howard Hughes Medical Institute) on this matter. I also made a plan of collaborative research with Dr. Osami Kanagawa (Department of Pathology) on the cytolytic and PFP induction in his murine killer T cell hybridoma by various cytokines.
6) I visited University of Alabama at March 2 - 3 and gave a seminar titled “CD2, LFA0-1 and other adhesion molecules involved in murine lymphocyte differentiation”. I discussed with Dr. Max Cooper (Howard Hughes Medical Institute) on this matter.
7) I visited MD Anderson Cancer Center at March 5 and gave a seminar entitled “Specific targeting therapy of human cancer using bispecific monoclonal antibody and ex vivo-activated lymphocytes”. I discussed with Drs. Kyogo Itoh (Departments of General Surgery and Immunology) and Hideyuki Saya (Department of Neuro-Oncology) on recent progress and future of cancer Immunotherapy in US and Japan.
8) I visited Stanford University School of Medicine at March 6 - 7, and gave a seminar titled “CD2, LFA-1 and other adhesion molecules involved in murine lymphocyte interactions.” I discussed with Dr. Leonard Herzenberg (Department of Genetics) on this matter. I also discussed with Dr. Lawrence Steinman (Department of Neurology and Neurological Sciences) on a restricted usage of T cell receptor repertoire in tumor infiltrating lymphocytes and its potential application to future adoptive immunotherapy.

(3) Yasuharu Nishimura, M.D.
Department of Genetics
Medical Institute of Bioregulation
Kyusyu University, 3-1-1 Maidashi, Higashi-Ku
Fukuoka 812, JAPAN

Sponsor and Host Institution:
Steven J. Burakoff, M.D.
Division of Pediatric Oncology
Dana-Farber Cancer Institute
44 Binney Street Boston, MA 02115
Dates ofVisit:
November 4 - 6 Fukuoka - Boston
Presentation of a seminar and discussion at the Department of Biochemistry and Molecular Biology, Harvard University
Host: Dr. J. L. Strominger
November 7
Discussion with Dr. S.J.Burakoff, Division of Pediatric Oncology, Dana-Farber Cancer Institute
November 8
Boston - New York
November 9
Presentation of a seminar and discussion at the Department of immunogenetics, Memorial Sloan Kettering Cancer Institute
Host: Dr. B. Dupont
November 10
New York - Fukuoka

Summary of Activities:
We have elucidated the HLA-linked immune suppression (Is) genes to several antigens in man and Is genes control low (non) responsiveness through the induction of CD4suppressor T cells by the particular alleles of HLA-DQ. CD4-suppressor T cells include CD8⁺T cell, CD8⁺T cell and CD4^-CD8^- T cell. The aim of my visit to U.S.A. was to discuss about the ligands and function of T cells, gene organization of HLA system and the markers of human suppressor T cells.
At the Dana-Farber Cancer Institute I discussed with Drs. S.J. Burakoff, M. Brenner, P. Bleicher and C.Morimoto. I learned that CD1 molecule was one of ligands for T cells and I have obtained several anti-CD1 monoclonal antibodies from them. I also learned the importance of CD45RA markers for the human CD4⁺ suppressor inducer T cells. At the Harvard University and Memorial Sloan Kettering Cancer Institute, I presented a seminar entitled “Genetic control of immune response by HLA-DQ in human and transgenic mice.” Dr. J. Strominger and his co-workers succeeded in the generation of an HLA-DQ negative human B cell line by the transfection of HLA-DQ antisense gene and I decided to collaborate with him to investigate the mechanism of immune suppression mediated by HLA-DQ. Drs. B. Dupont and G. Hammerling generated several lines of HLA class I transgenic mice and I have collaborated with them to exchange our HLA-DQ transgenic mice to their HLA class 1 transgenic mice.
During my visit, I have learned a lot of new data and obtained new ideas for our research projects. I also obtained many reagents useful for our research and succeeded to make collaborations with American scientists.