1: Generation of a Nonhuman Primate Model of Severe Combined Immunodeficiency Using Highly Efficient Genome Editing.
Science of the Month - September 2016
Cell Stem Cell.
2016 Jul 7;19(1):127-38. doi: 10.101.
Kenya Sato, Ryo Oiwa, Wakako Kumita, Rachel Henry, Tetsushi Sakuma, Ryoji Ito, Ryoko Nozu, Takashi Inoue, Ikumi Katano, Kengo Sato, Norio Okahara, Junko Okahara, Yoshihisa Shimizu, Masafumi Yamamoto, Kisaburo Hanazawa, Takao Kawakami, Yoshie Kametani, Ryuji Suzuki, Takeshi Takahashi, Edward J. Weinstein, Takashi Yamamoto, Yasubumi Sakakibara, Sonoko Habu, Jun-ichi Hata, Hideyuki Okano,* and Erika Sasaki
A joint research group led by Director Erika Sasaki of the Department of Marmoset Research, Central Institute for Experimental Animals (who also serves as a Project Professor at the Keio Advanced Research Centers (KARC), Keio University) and Professor Hideyuki Okano of the Department of Physiology, Keio University School of Medicine, has succeeded in creating the world's first primate model animal exhibiting a desired trait using genome-editing technology, and published their paper in the journal *Cell Stem Cell*. In 2009, this research group succeeded in creating the world's first transgenic common marmoset, a small and highly reproductive primate, and published their findings in *Nature*, which significantly advanced the development and research of human disease model animals. However, the targeted gene knockout technology used to create many human disease model mice could not be applied to primates, including marmosets. On the other hand, recently developed genome-editing technology has made it possible to directly modify genes in the fertilized eggs of various animal species, and this study demonstrated that it is possible to create human disease models in primates like the marmoset using genome editing. In the current study, the researchers used genome editing to inactivate the function of the IL2RG gene in marmoset fertilized eggs, creating marmosets with congenital immunodeficiency. It is expected that these immunodeficient marmosets will contribute to elucidating the pathology of human immunodeficiency and developing therapeutic models, as well as to verifying the efficacy and safety of new therapies in various organ regenerative medicine using human iPS cells.
(Hideyuki Okano, Professor, Department of Physiology, 62nd Graduating Class)
2: The microbiota in adaptive immune homeostasis and disease.
The journal *Nature* recently published a special feature on the "gut microbiota." It included reviews from six groups, including one by Dr. Jeffrey Gordon of Washington University, a recipient of the Keio Medical Science Prize. This paper is one of them. Together with Dr. Dan Littman of New York University, we introduced the latest findings, including our own research, on how specific gut bacterial species influence the differentiation and function of immune cells such as T cells and B cells, and contribute to maintaining host immune homeostasis. Furthermore, we discussed the molecular mechanisms by which an imbalance in the gut microbiota can lead to inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, autoimmune diseases like rheumatoid arthritis, multiple sclerosis, and type 1 diabetes, and other immune disorders such as allergies. In addition, we also described how gut bacteria have been found to influence the therapeutic effects of immune checkpoint inhibitor therapy for cancer, a topic of recent interest. To broadly cover the rapidly advancing research on the relationship between gut bacteria and immunity, we spent about six months reading numerous papers and had many discussions with Dr. Littman. We would be delighted if researchers outside of immunology and clinicians would also read it.
(Kenya Honda, Professor, Microbiology and Immunology, Equivalent to the 73rd Graduating Class)
Other Publications
1: Circulating Cell Death Biomarkers May Predict Survival in Human Lung Transplantation
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE.
97-105, 10.1164/rccm.201510-2115OC JUL 1 2016
Hashimoto Kohei, Besla Rickvinder, Zamel Ricardo, Juvet Stephen, Kim Hyunhee, Azad Sassan, Waddell Thomas K., Cypel Marcelo, Liu Mingyao, Keshavjee Shaf