Harvard Skin Disease Research Center
Brigham and Women's Hospital
Department of Dermatology
EBRC Room 505A
221 Longwood Avenue
Boston, MA 02115
My laboratory focuses on the study of tissue resident T cells in humans. We isolate and study the T cells in human lung, cervix, decidua and gastrointestinal tract but we have a particular interest in T cells at home to and reside within the skin.
Our studies focus on the study of T cells in normal human skin, in skin cancers and in inflammatory diseases. Our laboratory discovered that the skin of an adult individual contains approximately 20 billion memory T cells under normal, noninflamed conditions, nearly twice the number present in the entire circulation. These skin resident T cells are polarized effector memory T cells that provide potent and rapid local immune responses within the skin.
We also study the T cells from human cutaneous malignancies, including squamous cell carcinomas (SCC), Merkel cell carcinomas, malignant melanoma and cutaneous T cell lymphoma (CTCL). We have found that SCC evade immune responses by down regulating vascular E-selectin on tumor vessels and by recruiting noncutaneous Treg. In this way, the tumor excludes the population of skin homing T cells capable of recognizing and destroying it, while recruiting a population of cells that effectively suppresses local immunity. We and our collaborators have found that mycosis fungoides and Sézary syndrome, currently considered separate stages of CTCL, actually represent malignancies of two separate T-cell subsets. We have found that MF is a malignancy of skin resident effector memory T cells whereas Sézary syndrome is a malignancy of central memory T cells. This observation helps to explain the highly variable clinical presentations and prognoses of these two lymphomas, while the same time teaching us critical lessons about the biology of these two cell types.
In summary, my laboratory studies the T cells in normal and diseased human tissues with the dual goals of improving therapies for our patients and providing novel insights into human T cell biology.
Clark RA, Huang SJ, Murphy GF, Mollet IG, Hijnen D., Muthukuru M, Schanbacher CF, Edwards V., Miller DM, Kim JE, Lambert J., & Kupper TS. 2008. Human squamous cell carcinomas evade the immune response by downregulation of vascular E-selectin and recruitment of regulatory T cells. J Exp Medicine; 205:2221-2234.
Huang SJ, Hijnen D., Murphy GF, Kupper TS, Calarese, AW., Mollet IG., Schanbacher CF, Miller DM, Schmults C. & Clark RA. 2009. Imiquimod enhances IFN-γ production and effector function of T cells infiltrating human squamous cell carcinomas of the skin. J Invest Dermatol; 1523-1747.
Clark, RA. 2010. Skin resident T cells: the ups and downs of on site immunity; J Invest Dermatol; 130(2):362-70.
Clark, RA. 2011. Gone but not forgotten: lesional memory in psoriatic skin. J Invest Dermatol. Feb;131(2):283-5.
Clark, RA, Shackelton, JB, Watanabe, R, Calarese, A, Yamanaka, K, Campbell, JJ, Teague, JE, Kuo, HP, Hijnen, D, Kupper, TS. 2011. High Scatter T cells: a reliable biomarker for CTCL. Blood, First Edition Paper, prepublished online December 9, 2010; DOI 10.1182/blood-2010-05-287664.
Clark, R.A. , Watanabe R., Teague J.E., Schlapbach C., Tawa M.C., Adams N., Dorosario A.A., Chaney K.S., Cutler C.S., LeBoeuf N.R., Carter J.B., Fisher D.C., Kupper T.S. 2012. Skin effector memory T cells do not recirculate and provide immune protection in alemtuzumab treated CTCL patients. Science Translational Medicine. 4, 117ra117.
Gehad, A., Lichtman, M., Schmults, C., Teague, J.E., Calarese, A., Jiang, Y., Watanabe, R. and Clark, R.A. 2012. Nitric oxide-producing myeloid-derived suppressor cells inhibit vascular E-selectin expression in human squamous cell carcinomas. J Invest Dermatol. In press.
Last Update: 1/6/2014