Takatoku Oida, Ph.D.

Research Fellow

Center for Neurologic Diseases
Brigham and Women's Hospital
Harvard Medical School, NRB641
77 Avenue Louis Pasteur
Boston, MA 02115

T: (617) 525-5738

E:toida@rics.bwh.harvard.edu

 


Education
1990 BA (Science) Kyoto University, Japan
1992 MA (Science) The University of Tokyo, Japan
1999 Ph.D. (Life Science) The University of Tokyo, Japan

Positions
1992-1995 Researcher, Suntory Pharmaceutical Center, Japan
1999-2002 Research fellow, Brigham and Women's Hospital, Boston, MA
2002-2004 Research fellow, National Institutes of Health, Bethesda, MD
2004-2006 Research fellow, Japan Science and Technology Agency & Assistant professor, Kyoto University, Japan
2006-2007 Research fellow, RIKEN RCAI, Japan
2007-present Reseach fellow, Weiner Lab

Personal background
After I obtained my master degree, I got a job in a pharmaceutical company, which was one of emerging bio-ventures. The company had a couple of peptide hormones and cytokines as their developing products. By that time people began to realize that those protein drugs had to be injected frequently because their half-lives were usually quite short. This means that only hospitalized patients were the possible targets for those products. To increase their applications, other administration methods were desperately needed. One of my missions at the pharmaceutical company was to develop drug delivery systems (DDS) for protein drugs. Nasal administration and oral administration of peptide/protein drugs were the ultimate goal. However, it was not easy, especially for oral delivery, because, as a matter of course, proteins are digested in stomach and in intestine. We,and others, used insulin as a model drug for this kind of DDS research. - One day. I met a paper - which described that oral administration of insulin prevented diabetes by a mechanism called "oral tolerance". They used insulin as simple PBS solution without any DDS modifications. It seemed that insulin did not have to be absorbed into the blood stream as a native form. This was quite shocking to me as a person involved in DDS research. The author of the paper was Dr. Weiner. I questioned myself "how the orally administered protein works in the intestine?" Dr. Weiner wrote TGF-beta was the effector molecule. Since then, TGF-beta has been obsessing my mind all the time. I decided to go back to the academy. It was 14 years ago, but I feel as if it was yesterday. However, the TGF-beta matter is more complicated than I thought. I would say there are misunderstanding and confusion in this area.

Research direction
We know well about biological functions of TGF-beta. We can commercially obtain pure recombinant TGF-beta and we can add it into a culture to check its function. On the other hand, we do not know how TGF-beta is produced by immune cells. Pre-pro-TGF-beta has to be processed intracellularly to become latent TGF-beta, and it is secreted as the latent form. Latent TGF-beta cannot bind to the TGF-beta receptors, so TGF-beta production by itself does not necessarily mean generation of TGF-beta signaling. TGF-beta must be further processed to be active. We do not have any data how these intracellular processing and extracellular processing are done. We can purchase ELISA systems to detect the active form of TGF-beta. Curiously in most cases, however, we cannot see any active TGF-beta in T cell cultures. (Some people would say "yes, I can", and this is also one of the complex issues). Most people measure total (= latent) TGF-beta, saying just because there is no active TGF-beta. Problem is that although they measure inactive form TGF-beta, they discuss as if what they got is biologically active. This is one of the reasons of the confusion. We should go back to basic questions: Don't immune cells really produce active TGF-beta? Or is it because the method (ELISA) not suitable? Is TGF-beta really a soluble cytokine as people think? First, we need to have appropriate detection systems to measure active TGF-beta. Bioassay is one of the good candidates to see TGF-beta activity. Second, we need to reveal the biosynthesis of TGF-beta: processing, intracellular transport, secretion, extracellular localization, and activation. We should find molecules involved in these processes. Let's things make clear by our hands.

Happy memories
Although I quite the job, days spent in the pharmaceutical company was my best memory. We worked as a team for shared objectives. My boss, Yujiro-san, always understood and supported me. They backed me up even when I decided to leave. I made up my mind that I would never see them again until my dream came true. (This is a Japanese way of thinking, isn't it?)
I met friends with the same mind during my Ph.D. course. Takahashi-san, Amano-san, and Hirata-san. They were so straight to their ideals, and by that reason they had hardships in their lives. However, this is the point we feel mutual respect in. I hope they won't change and are doing well.
Even in a hard situation, I had colleagues who could enjoy a science talk. Nishioka-san, Hirota-san, Sugimoto-san, and Kyo-chan. I admire not only their sense of science, but also their pure hart. Some days we'll meet again and have good sake (Japanese rice alcohol) for cheers.

Publications
Sugimoto N, Oida T, Hirota K, Nakamura K, Nomura T, Uchiyama T, Sakaguchi S. Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis.Int Immunol. 2006,18,1197-1209

Oida T, Xu L, Weiner HL, Kitani A, Strober W. TGF-beta-mediated suppression by CD4+CD25+ T cells is facilitated by CTLA-4 signaling. J Immunol. 2006, 177, 2331-2339

Oida T, Zhang X, Goto M, Hachimura S, Totsuka M, Kaminogawa S, Weiner HL. CD4+CD25- T cells that express latency-associated peptide on the surface suppress CD4+CD45RBhigh-induced colitis by a TGF-beta-dependent mechanism. J Immunol. 2003,170, 2516-2522

Monsonego A., Imitola J., Zota V., Oida T, Weiner HL. Microglia-Mediated Nitric Oxide Cytotoxicity of T Cells Following Amyloid beta-Peptide Presentation to Th1 Cells. J Immunol 2003; 171: 2216-2224.

Suzuki K, Oida T, Hamada H, Hitotsumatsu O, Watanabe M, Hibi T, Yamamoto H, Kubota E, Kaminogawa S, Ishikawa H. Gut cryptopatches: direct evidence of extrathymic anatomical sites for intestinal T lymphopoiesis. Immunity 2000; 13(5):691-702

Oida T, Suzuki K, Nanno M, Kanamori Y, Saito H, Kubota E, Kato S, Itoh M, Kaminogawa S, Ishikawa H. Role of gut cryptopatches in early extrathymic maturation of intestinal intraepithelial T cells. J Immunol 2000; 164(7):3616-26

Ishikawa H, Saito H, Suzuki K, Oida T, Kanamori Y. New gut associated lymphoid tissue "cryptopatches" breed murine intestinal intraepithelial T cell precursors. Immunol Res 1999; 20(3):243-50

Oida T, Sako Y, Kusumi A. Fluorescence lifetime microscopy (flimscopy). Methodology development and application to studies of endosome fusion in single cells. Biophys J 1993; 64(3):676-85