Faculty

Taku Kambayashi, M.D, Ph.D.

faculty photo
Associate Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
288 JMB, 3620 Hamilton Walk
Philadelphia, PA 19104
Office: 215-746-7610
Fax: 215-573-9261
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.
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Description of Research Expertise

https://kambayashilab.com/

Research interests:
Regulation of T cell responses; Signal transduction; regulatory T cell expansion and homeostasis; Regulation of skin barrier function

Keywords:
CD8+ T cells, CD4+ T cells, Regulatory T cells, Signal Transduction, Cellular Immunology, Skin barrier function

Specific Projects:

1) Immune-mediated control of sebum secretion by the skin
We have recently discovered that T cells that are stimulated by a keratinocyte-derived cytokine TSLP induces sebum secretion from sebaceous glands of the skin. Sebum is a high calorie lipid-rich substance that provides barrier protection to the skin. When this sebum secretion system is put into high gear, we found that high fat diet-fed mice selectively lose adipose tissue and lower their tissue triglyceride levels, providing benefit to obesity-related disorders. At homeostasis, we believe that the T cell/TSLP/sebum axis is important for providing skin barrier function in response to pathogens and commensals. Ongoing projects involve the investigation of the mechanism by which TSLP-stimulated T cells promote sebum secretion and how this axis interacts with skin commensals and pathogens.

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.

3) DGK as a novel checkpoint target for reactivation of exhausted T cells
Diacylglycerol (DAG) is an important second messenger downstream of T cell activation through their T cell receptor (TCR). DAG is negatively regulated by a kinase called DAG kinase (DGK), which phosphorylates DAG into phosphatidic acid, thereby terminating DAG-mediated signaling. Our previous work has shown that DGK deficiency leads to heightened NK cell and T cell activation and resistance to PD-1-mediated inhibition. Ongoing projects in the lab involve the investigation of how DGK and its downstream pathways (such as ERK) affect T cell responses during chronic viral infection with LCMV clone 13.

4) Developing a mouse model of Idiopathic Multicentric Castleman Disease (iMCD)
iMCD is a rare but life-threatening cytokine storm disorder of unknown etiology. To understand more about iMCD pathogenesis, we have been studying the signaling pathways and transcriptomics in cells from iMCD patients. Through this work, we have identified a number of key signaling molecules that might be important in iMCD pathogenesis including mTOR and IFN signaling. We are currently developing mouse models of iMCD to mechanistically test the role of these pathways in this devastating disease.

Lab personnel:
Ruth Choa, PhD, Medical Student
Shohei Harabuchi, MD, PhD, Postdoctoral Fellow
Jordan Harris, MD/PhD Student
Dorottya Laczko, MD, PhD, Postdoctoral Fellow
Mariko Okumura, Research Specialist
Lillian Sun, MD/PhD Student (rotation)
Paulina Tran, DO, Postdoctoral Fellow
Yuichi Yokoyama, MD, PhD, Postdoctoral Fellow

Description of Clinical Expertise

Transfusion Medicine
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Last updated: 04/29/2022
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