Specialty Division

Transfusion Medicine & Therapeutic Pathology, Immunobiology and Experimental Pathology

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

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
Flash Talk Award, 6th Japan-US Science Forum, 2021
Membership to Henry Kunkel Society, 2022
Lady Barbara Colyton Prize for Autoimmune Research, University of Pennsylvania, 2022
STAT Madness Crowd Favorite Award, 2022
STAT Summit Breakthrough Science Award, 2022

Memberships and Professional Organizations

American Association of Immunologists, 2003 - Present
Academy of Clinical Laboratory Physicians and Scientists, 2007 - 2009
American Association of Blood Banks, 2007 - 2019
American Academy of Allergy, Asthma, and Immunology (AAAAI), 2009 - 2010
National Blood Foundation, 2009 - 2019
American Society of Clinical Pathology, 2009 - 2010
Arthritis Foundation, 2010 - 2010
American Society of Hematology, 2010 - 2015
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
US Department of Defense, 2020 - 2020
Henry Kunkel Society, 2022 - Present

Web Links

Selected Publications