Immunology Faculty Member - Shawn Demehri, MD, PhD.

Shawn Demehri, MD, PhD.

Assistant Professor

Department of Dermatology and MGH Cancer Center
Massachusetts General Hospital
Harvard Medical School
Cutaneous Biology Research Center
Building 149 13th Street, 3rd floor
Charlestown MA 02129
Email: sdemehri1@mgh.harvard.edu
Visit my lab page here.



Our laboratory investigates the role of the immune system in modulating the early stages of cancer development in order to harness its anti-tumor properties to combat cancer. To date, several cancer immunotherapeutic drugs have been developed with proven efficacy; however, these drugs are used mainly against late stage cancers to augment the anti-tumor immune response that has already formed against cancer cells. Our research is focused on identifying the immune mechanisms that drive an immune activation sufficient to prevent cancer formation from pre-cancerous lesions. This approach raises a great opportunity to discover novel immune pathways that can be leveraged in cancer therapy and prevention.

To pursue this goal, our laboratory is currently focused on three areas of research:

(1) Mechanisms of T cell activation that suppress carcinogenesis. Specifically, our laboratory has studied the mechanism of thymic stromal lymphopoietin (TSLP) in evoking tumor resistance. TSLP is an epithelial-derived cytokine that plays a central role in stimulating CD4+ T helper 2 (Th2)-mediated allergic diseases like atopic dermatitis and asthma. We have shown that high TSLP levels establish a dominant anti-tumorigenic immune environment preventing cancer promotion. Currently, our team investigates the detailed mechanism of TSLP anti-tumor function against solid cancers and examines its application for the treatment of pre-cancerous skin lesions in patients.

(2) Mechanisms of NK cell recruitment and activation at the site of a developing cancer. Our laboratory is utilizing a virally encoded ligand for NK cells to determine the combination of signals necessary to activate NK cells against early stages of carcinogenesis and to identify the mechanism of anti-tumor immunity mounted by the activated NK cells in order to block cancer promotion and progression.

(3) Mechanisms of tumor promotion by the immune system. Chronic inflammatory conditions can predispose patients to cancer; however, the mechanism of such immune-mediated tumor promotion is unclear. To determine this mechanism, our laboratory studies skin carcinogenesis as an ideal cancer model in which the spatial and temporal relationship between inflammation and cancer development can be determined with exceptional precision. We are currently investigating the immune mechanisms that promote skin cancer development in the context of chronic allergic contact dermatitis and cutaneous lupus.



Last Update: 1/25/2017



Publications

 

1. Demehri, S., Liu, Z., Lee, J., Lin, M. H., Crosby, S. D., Roberts, C. J., Grigsby, P. W., Miner, J. H., Farr, A. G., and Kopan, R. (2008). Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity. PLoS Biol 6, e123.

2. Demehri, S., Turkoz, A., and Kopan, R. (2009b). Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironment. Cancer cell 16, 55-66.

3. Demehri, S., Turkoz, A., Manivasagam, S., Yockey, L. J., Turkoz, M., and Kopan, R. (2012). Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin. Cancer cell 22, 494-505.

4. Demehri, S., Cunningham, T.J., Manivasagam, S., Ngo, K.H., Moradi Tuchayi, S., Reddy, R., Meyers, M.A., DeNardo, D.G., and Yokoyama, W.M. Thymic stromal lymphopoietin blocks early stages of breast carcinogenesis. J Clin Invest 2016; 126(4): 1458-70.

5. Cunningham, T.J., Tabacchi, M., Eliane, J.P., Tuchayi, S.M., Manivasagam, S., Mirzaalian, H., Turkoz, A., Kopan, R., Schaffer, A., Saavedra, A.P., Wallendorf, M., Cornelius, L.A., and Demehri, S. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest 2017; 127(1): 106-116.



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