PEOPLE

Taku Kambayashi, MD, PhD

Associate Professor of Pathology and Laboratory Medicine
University of Pennsylvania Perelman School of Medicine

Contact Information288 JMB, 3620 Hamilton Walk
Philadelphia, PA 19104
Office: 215-746-7610
Fax: 215-573-9261

Email: taku.kambayashi@uphs.upenn.edu

Specialty Division

Transfusion Medicine & Therapeutic Pathology, Immunobiology and Experimental Pathology

Research Expertise

Research interests:
Regulation of T cell responses; regulatory T cell expansion and homeostasis; Natural killer (NK) cell education and signaling

Keywords:
CD8+ T cells, CD4+ T cells, Regulatory T cells, NK cells, Signal Transduction, Cellular Immunology, Antigen Presentation

Research summary:

1) Regulation of T cell responses
T cells are pivotal players in the immune response. They are beneficial in combating infections and cancer but can also be harmful in autoimmunity and immunopathologic states. T cell activation is primarily initiated by intracellular signals emanating through their T cell receptor. These signals can be further modified by engagement of other cell surface receptors and by negative regulators of signaling. Currently, we study the role of the NK cell receptor NKG2D in controlling T cell activation. In addition, we are investigating the roles of negative regulators of calcium and daicylglycerol signaling in T cell activation and differentiation.

2) Regulatory T cell expansion and homeostasis
In addition to the cell-intrinsic regulation of T cell activation as described above, T cells are controlled cell extrinsically by regulatory T cells. Regulatory T cells represent a subset of CD4+ T cells that possess the ability to suppress the activation and expansion of other conventional CD4+ T cells. They are distinguished from conventional T cells by constitutive expression of CD25 and the transcription factor Foxp3. The importance of regulatory T cells is evidenced by the severe autoimmunity that develops in mice and humans lacking regulatory T cells. We are actively investigating how signal transduction processes affect the development, homeostasis, expansion, and function of regulatory T cells. We translate our findings to therapeutic approaches in the prevention of inflammatory diseases such as multiple sclerosis, graft-versus-host disease, diabetes, rheumatoid arthritis, and inflammatory bowel disease.

4) NK cell education and signaling
NK cells are innate immune cells that provide a critical line of defense against intracellular pathogens and tumors by displaying cytotoxicity and producing immune-activating cytokines. One key mechanism that regulates their activation involves the expression of activating receptors that are finely counterbalanced by inhibitory MHC class I-binding receptors. Thus, the interaction of NK cells with abnormal cells that have decreased MHC class I expression relieves the inhibition conferred by the MHC-binding inhibitory receptors, leading to activation and cytotoxicity by the NK cell. NK cells heterogeneously express one or more of the many inhibitory receptors, which are acquired by NK cells during later stages of their development. The heterogeneity of NK cell receptor expression allows NK cells to discriminate between cells expressing normal and abnormal amounts of various MHC class I molecules. As the signaling requirements of these receptors during development and effector function remain unclear, we have been investigating the signal transduction pathways during NK cell activation. In doing so, we have identified some key signaling molecules that are necessary for proper acquisition of MHC-binding inhibitory receptors during development. We are further investigating the molecular mechanisms that are responsible for regulating inhibitory receptor acquisition during NK cell development and how it relates to the functional outcome of the NK cell response.

Rotation Projects are available in all areas

Lab personnel:
Mobin Karimi, Postdoctoral Fellow
Theresa Leichner, PhD Student
Mariko Okumura, Research Specialist
Atsushi Satake, Postdoctoral Fellow
Amanda Schmidt, PhD Student
Enjun Yang, PhD Student

Clinical Expertise

Transfusion Medicine

Itmat Expertise

Cell signaling in immune cells and the impact of these pathways on inflammatory diseases.

Graduate Groups

Immunology

Education

B.S. (Biomedical Engineering), Johns Hopkins University, Baltimore, MD, 1993
Ph.D. (Immunology), Emory University, Atlanta, GA, 2002
M.D. (Medicine), Emory University, Atlanta, GA, 2004

Specialty Certification

Clinical Pathology - American Board of Pathology, 2008
Transfusion Medicine - American Board of Pathology, 2008

Postgraduate Training

Resident in Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, 2004-2007
Post-doctoral Fellow in Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, 2005-2008
Transfusion Medicine Fellow, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, 2007-2008

Awards and Honors

Far East Science Award, Proctor & Gamble, 1989
Outstanding Research Award, Otsuka America Pharmaceuticals, 1996
Woodruff Scholar Award, Emory University, 1996
Paul E. Strandjord Young Investigator Award with Distinction, ACLPS, 2007
National Blood Foundation Scholar Award, 2009-2011
American Society of Hematology Junior Faculty Scholar Award, 2010-2012
Kevin Salhany Award for Excellence in Clinical Teaching, University of Pennsylvania, 2012
Membership to the American Society of Clinical Investigation, 2012
David B Pall Prize for Innovation in Transfusion Medicine, AABB, 2012
American Asthma Foundation Scholar Award, 2014
The Simon Flexner Award, University of Pennsylvania, 2015

Memberships and Professional Organizations

American Association of Immunologists, 2003 - Present
American Association of Blood Banks, 2007 - Present
Academy of Clinical Laboratory Physicians and Scientists, 2007 - 2009
American Academy of Allergy, Asthma, and Immunology (AAAAI), 2009 - 2010
National Blood Foundation, 2009 - Present
American Society of Clinical Pathology, 2009 - 2010
American Society of Hematology, 2010 - Present
Arthritis Foundation, 2010 - 2010
National Institute of Diabetes and Digestive and Kidney Diseases, 2012 - 2015
American Society of Clinical Investigation, 2013 - Present
Allergy, Immunology, and Transplantation Research Committee, NIH Study Section, 2016 - Present

Web Links


Selected Publications