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Craig T. Morita, MD, PhD

Portrait
Professor of Internal Medicine - Immunology

Contact Information

Primary Office
400F EMRB
Iowa City, IA 52242
319-484-4608

Education

AB, University of California, Berkeley, California
MD, University of California School of Medicine, San Francisco, California
PhD, Immunology, University of California School of Medicine, San Francisco, California
Internship, Internal Medicine, University of California, School of Medicine
Resident, Internal Medicine, Boston University School of Medicine, Boston, MA
Fellow, Research in Medicine, Harvard Medical School
Fellow, Dept of Rheumatology & Immunology, Brigham & Women's Hospital, Boston, MA

Licensure and Certifications

Rheumatology
American Board of Internal Medicine - Harvard Medical School

Education/Training Program Affiliations

Interdisciplinary Graduate Program in Immunology, Interdisciplinary Graduate Program in Translational Biomedicine, Medical Scientist Training Program

Research Summary

My lab focuses on the study of human ?? T cells and nonpeptide antigens. T cells are a distinct subset of T cells that function to bridge innate and adaptive immunity by recognizing nonpeptide, isoprenoid metabolites and by performing unique roles not played by ?? T cells. ?? T cells are very important in human microbial immunity as evidenced by the large expansions of V?2V?2 T cells (up to 1 in 2 circulating T cells) that occur during many bacterial and parasitic infections. Moreover, once activated, V?2V?2 T cells kill most types of tumors by recognizing them using the NK receptors that they express. Thus, efforts are ongoing to determine how to use V?2V?2 T cells for cancer immunotherapy We have found that human ?? T cells use their V?2V?2 antigen receptors to recognize essential phosphorylated metabolites in isoprenoid biosynthesis. Bacteria and protozoan parasites use a different metabolic pathway to make isoprenoids than humans which use the mevalonate pathway. V?2V?2 T cells recognize one of the intermediates in this pathway, termed HMBPP. They also recognize the self-metabolite, IPP, which accumulates in cells after aminobisphosphonate drug treatment. One area of focus of the lab is to determine how these small phosphoantigens are presented to V?2V?2 T cells by identifying its novel antigen presenting molecule. We are also working to identify a novel bacterial antigen produced by Staphylococcus aureus and other Gram-positive cocci despite their use of the mevalonate pathway, the biochemical pathway responsible for its synthesis, and to determine the role of V?2V?2 T cells in immunity to Gram-positive cocci. A second area of study has focused on the development of memory in ?? T cells. We have found that distinct memory subsets of V?2V?2 T cells exist. These V?2V?2 subsets have different migratory and functional abilities. The different migration is due to differential expression of adhesion molecules and chemokine receptors that determine the homing capabilities of cells. Our present studies focus on the factors that control the generation of memory V?2V?2 T cells and the relative importance of the different memory subsets in bacterial and tumor immunity. We are also studying IL-17A and IL-22 production by V?2V?2 T cells to determine the cytokines and signals controlling their differentiation into Th17-like cells and their functional significance in human microbial immunity and autoimmunity. A third area of study is to develop ?? vaccines for bacterial infections and for cancer immunotherapy. In clinical trials, stimulating V?2V?2 T cells has resulted in partial and complete remissions in some cancer patients with lymphoma, prostate cancer, and renal cell carcinoma. We are engineering the metabolism of vaccine bacteria to make them overproduce the HMBPP antigen as vaccines for ?? T cells. We are also studying new lipophilic bisphosphonates. In preclinical studies, we are testing these vaccines in monkeys and in immunodeficient mice transplanted with human blood cells.

Publications

Wang, H., Nada, M. H., Tanaka, Y., Sakuraba, S. & Morita, C. T. (2019). Critical Roles for Coiled-Coil Dimers of Butyrophilin 3A1 in the Sensing of Prenyl Pyrophosphates by Human V?2Vd2 T Cells. Journal of immunology (Baltimore, Md. : 1950), 203(3), 607-626. PMID: 31227581.

Tagod MSO,, Mizuta, S., Sakai, Y., Iwasaki, M., Shiraishi, K., Senju, H., Mukae, H., Morita, C. T. & Tanaka, Y. (2019). Determination of human ?d T cell-mediated cytotoxicity using a non-radioactive assay system. Journal of immunological methods, 466, 32-40. PMID: 30654042.

Mizuta, S., Tagod MSO,, Iwasaki, M., Nakamura, Y., Senju, H., Mukae, H., Morita, C. T. & Tanaka, Y. (2019). Synthesis and Immunomodulatory Activity of Fluorine-Containing Bisphosphonates. ChemMedChem, 14(4), 462-468. PMID: 30637982.

Mizuta, S., Tagod MSO,, Iwasaki, M., Nakamura, Y., Senju, H., Mukae, H., Morita, C. T. & Tanaka, Y. (2019). Synthesis and Immunomodulatory Activity of Fluorine-Containing Bisphosphonates. ChemMedChem. PMID: 30637982.

White, W. B., Saag, K. G., Becker, M. A., Borer, J. S., Gorelick, P. B., Whelton, A., Hunt, B., Castillo, M. & Gunawardhana, L. (2018). Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. The New England journal of medicine, 378(13), 1200-1210. PMID: 29527974.

Tanaka, Y., Murata-Hirai, K., Iwasaki, M., Matsumoto, K., Hayashi, K., Kumagai, A., Nada, M. H., Wang, H., Kobayashi, H., Kamitakahara, H., Okamura, H., Sugie, T., Minato, N., Toi, M. & Morita, C. T. (2017). Expansion of human ?d T cells for adoptive immunotherapy using a bisphosphonate prodrug. Cancer science. PMID: 29288540.

Sakai, Y., Mizuta, S., Kumagai, A., Tagod MSO,, Senju, H., Nakamura, T., Morita, C. T. & Tanaka, Y. (2017). Live Cell Labeling with Terpyridine Derivative Proligands to Measure Cytotoxicity Mediated by Immune Cells. ChemMedChem, 12(23), 2006-2013. PMID: 29110403.

Tanaka, Y., Iwasaki, M., Murata-Hirai, K., Matsumoto, K., Hayashi, K., Okamura, H., Sugie, T., Minato, N., Morita, C. T. & Toi, M. (2017). Anti-Tumor Activity and Immunotherapeutic Potential of a Bisphosphonate Prodrug. Scientific reports, 7(1), 5987. PMID: 28729550.

Nada, M. H., Wang, H., Workalemahu, G., Tanaka, Y. & Morita, C. T. (2017). Enhancing adoptive cancer immunotherapy with V?2Vd2 T cells through pulse zoledronate stimulation. Journal for immunotherapy of cancer, 5, 9. PMID: 28239463.

Nada, M. H., Wang, H., Workalemahu, G., Tanaka, Y. & Morita, C. T. (2017). Enhancing adoptive cancer immunotherapy with V?2Vd2 T cells through pulse zoledronate stimulation. Journal for immunotherapy of cancer, 5, 9. PMID: 28239463.

Matsumoto, K., Hayashi, K., Murata-Hirai, K., Iwasaki, M., Okamura, H., Minato, N., Morita, C. T. & Tanaka, Y. (2016). Targeting Cancer Cells with a Bisphosphonate Prodrug. ChemMedChem, 11(24), 2656-2663. PMID: 27786425.

Matsumoto, K., Hayashi, K., Murata-Hirai, K., Iwasaki, M., Okamura, H., Minato, N., Morita, C. T. & Tanaka, Y. (2016). Targeting Cancer Cells with a Bisphosphonate Prodrug. ChemMedChem, 11(24), 2656-2663. PMID: 27786425.

Collins, C. C., Bashant, K., Erikson, C., Thwe, P. M., Fortner, K. A., Wang, H., Morita, C. T. & Budd, R. C. (2016). Necroptosis of Dendritic Cells Promotes Activation of x03B3;d T Cells. Journal of innate immunity. PMID: 27431410.

Tanaka, Y., Morita, C. T. (2016). Anti-PD-1 and anti-PD-L1 mAbs. In Y. Yamaguchi (Eds.) Immunotherapy of cancer: an innovative treatment comes of age. Tokyo: Springer.

Collins, C. C., Bashant, K., Erikson, C., Thwe, P. M., Fortner, K. A., Wang, H., Morita, C. T. & Budd, R. C. (2016). Necroptosis of Dendritic Cells Promotes Activation of ?d T Cells. Journal of innate immunity, 8(5), 479-92. PMID: 27431410.

Wang, H., Morita, C. T. (2015). Sensor Function for Butyrophilin 3A1 in Prenyl Pyrophosphate Stimulation of Human V?2Vd2 T Cells. Journal of immunology (Baltimore, Md. : 1950), 195(10), 4583-94. PMID: 26475929.

Wang, H., Morita, C. T. (2015). Sensor Function for Butyrophilin 3A1 in Prenyl Pyrophosphate Stimulation of Human V?2Vd2 T Cells. Journal of immunology (Baltimore, Md. : 1950), 195(10), 4583-94. PMID: 26475929.

Workalemahu, G., Wang, H., Puan, K. J., Nada, M. H., Kuzuyama, T., Jones, B. D., Jin, C. & Morita, C. T. (2014). Metabolic engineering of Salmonella vaccine bacteria to boost human V?2Vd2 T cell immunity. Journal of immunology (Baltimore, Md. : 1950), 193(2), 708-21. PMID: 24943221.

Wang, H., Henry, O., Distefano, M. D., Wang, Y. C., Räikkönen, J., Mönkkönen, J., Tanaka, Y. & Morita, C. T. (2013). Butyrophilin 3A1 plays an essential role in prenyl pyrophosphate stimulation of human V?2Vd2 T cells. Journal of immunology (Baltimore, Md. : 1950), 191(3), 1029-42. PMID: 23833237.

Idrees, A. S., Sugie, T., Inoue, C., Murata-Hirai, K., Okamura, H., Morita, C. T., Minato, N., Toi, M. & Tanaka, Y. (2013). Comparison of ?d T cell responses and farnesyl diphosphate synthase inhibition in tumor cells pretreated with zoledronic acid. Cancer science, 104(5), 536-42. PMID: 23387443.

Sugie, T., Murata-Hirai, K., Iwasaki, M., Morita, C. T., Li, W., Okamura, H., Minato, N., Toi, M. & Tanaka, Y. (2013). Zoledronic acid-induced expansion of ?d T cells from early-stage breast cancer patients: effect of IL-18 on helper NK cells. Cancer immunology, immunotherapy : CII, 62(4), 677-87. PMID: 23151944.

Giner, J. L., Wang, H. & Morita, C. T. (2012). Synthesis and immunological evaluation of the 4-ß-glucoside of HMBPP. Bioorganic & medicinal chemistry letters, 22(2), 811-3. PMID: 22222033.

Wang, H., Sarikonda, G., Puan, K. J., Tanaka, Y., Feng, J., Giner, J. L., Cao, R., Mönkkönen, J., Oldfield, E. & Morita, C. T. (2011). Indirect stimulation of human V?2Vd2 T cells through alterations in isoprenoid metabolism. Journal of immunology (Baltimore, Md. : 1950), 187(10), 5099-113. PMID: 22013129.

Ness-Schwickerath, K. J., Morita, C. T. (2011). Regulation and function of IL-17A- and IL-22-producing ?d T cells. Cellular and molecular life sciences : CMLS, 68(14), 2371-90. PMID: 21573786.

H, B., G, P., J, M., Ct, M., S, I., R, M. & Mb, B. (1990). Recognition of mycobacterial antigens by gamma delta T cells. Research in immunology, 141(7), 645–651. PMID: 2151351.