Shadmehr (Shawn) Demehri, M.D., Ph.D.

Demehri Lab

The focus of the Demehri laboratory is to determine the role of the immune system in regulating the early stages of cancer development in order to harness its anti-tumor potential for cancer therapy.

Overview

Shadmehr (Shawn) Demehri, M.D., Ph.D.
Assistant Professor of Dermatology
Massachusetts General Hospital Cancer Center
Harvard Medical School

Research Summary

The focus of the Demehri laboratory is to determine the role of the immune system in regulating the early stages of cancer development in order to harness its anti-tumor potential for cancer therapy. To date, several cancer immunotherapies have been developed with proven efficacy against late-stage cancers; however, the role of the immune system in preventing the early development of cancer remains uncertain. The research in our laboratory 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.

Immune Regulation of Cancer Development

Immune Regulation of Cancer Development

Read the Demehri Annual Report in Full

Group Members

Shadmehr (Shawn) Demehri, M.D., Ph.D.
Assistant Professor
Massachusetts General Hospital
Harvard Medical School

B.S.: Biology, Washington State University
M.D.: Washington University in St. Louis
Ph.D.: Cell and Molecular Biology, Washington University in St. Louis
Residency: Dermatology, Barnes Jewish Hospital/ Washington University
Postdoctoral Fellowship: Immunology, Washington University in St. Louis

 


  • Mark Bunting, Ph.D.

    Postdoctoral Fellow

    B.S.: Biomedical Science, The University of Adelaide, Australia
    B.S. (Honours): Immunology, The University of Adelaide, Australia
    Ph.D.: Immunology, The University of Adelaide, Australia

    Mark obtained his Ph.D. in chemokine biology focusing on the atypical decoy chemokine receptor, ACKR4/CCX-CKR. ACKR4 expression in the skin was found to be critical for robust trafficking of antigen-loaded dendritic cells to the lymphatic endothelium while thymic ACKR4 expression was required for normal thymocyte development. The absence of ACKR4 led to development of a Sjögren’s syndrome-like disease. Mark then worked as a postdoctoral fellow in the Bone Marrow Transplantation laboratory at QIMR in Brisbane, Australia to understand how graft-versus-host disease impacts NK cell reconstitution post-transplant and the contribution of mucosal innate lymphoid cells to providing protection from this disease. His current work in the Demehri laboratory is focused on NK cell activation and tumor immunity.


  • Kaitlin Dempsey

    Research Technician

    B.A.: Biochemistry, Smith College
    M.S.: Human Physiology, Boston University

    Katie comes to our lab having recently completed a Master of Science degree in Human Physiology from Boston University. Though her background is in clinical research and patient care, she hopes to gain laboratory experience and advance her skills to further contribute to laboratory studies. She looks to apply her interest in genetics to the field of cancer biology, immunology and gain knowledge of the innate immune system’s role in cancer.


  • Tatsuya Hasegawa, Ph.D.

    Research Fellow

    B.S.: Pharmacy, Kanazawa University
    Ph.D.: Pharmacy, Kanazawa University

    Tatsuya received his Ph.D. degree in Pharmacy in 2008 studying the role of antioxidants compounds from E. globulus and Sasa kurilensis as anti-inflammatory as well as anti-melanogenesis agents. During his postdoctoral training, Tatsuya studied the role of inflammasome and autophagy in skin inflammatory responses. He is interested in understanding the changes in skin immunity in response to cellular damage like UV radiation.


  • Kenneth Ngo

    Research Technician (Lab Manager)

    B.S.: Biomedical Sciences, Boston University
    Research Animal Specialist: Boston University

    Ken joined our lab as a BU student with strong interest in the field of cancer biology and immunology. In the upcoming months, he will be assisting the Demehri lab in the effort to identify the factors in a Th2 immune environment that are critical for suppression of early stages of cancer development. He hopes to pursue a master in bioinformatics, so that he can further advance his skill set and contribute to the research in the lab.


  • Erik Schiferle

    Research Technician

    B.A.: English/Pre-Med, Columbia University
    M.S.: Materials Science and Engineering (Biomaterials), Boston University (Degree in process)

    Erik joined our lab as a student pursuing his Master of Science degree in Materials Science and Engineering (Biomaterials) from Boston University. He has been involved in research at the Physiology and Biophysics Department of the University at Buffalo and the Ames National lab. Erik has joined our research effort into understanding the role of NK cells in tumor immunity and assists in other laboratory studies on cancer immunology.


  • Anniek Zaalberg

    Graduate Student

    B.S.: Biomedical Sciences, VU University
    M.S.: Oncology, VUmc School of Medical Sciences (Degree in process)

    Anniek received her B.S. in Biomedical Sciences from VU University Amsterdam and she is currently enrolled in the Oncology Master’s degree program. Her previous research was focused on the use of LINE-1 as a biomarker for early stage colon cancer, HLA-G expression in colorectal cancer and associated liver metastases and the differential dependence in recruiting and activating specific Y-family TLS polymerases in the DNA damage response. Anniek has a great interest in cancer immunology and she recently joined our lab as a Research Scholar to investigate the mechanism of skin cancer development in the context of chronic skin inflammatory conditions.


  • Anna Zemel, Ph.D.

    Postdoctoral Fellow

    B.S.: Chemical Engineering and Biotechnology, University Center of Samaria
    M.S.: Microbiology and Clinical Immunology, Sackler Faculty of Medicine, Tel-Aviv University
    Ph.D.: Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University

    Anna’s background is in the field of immunology and neurobiology. Her previous research was focused on resolving the mechanism of cognitive and neural deficits in the variety of neurodegenerative diseases using biochemical techniques and mouse models. In addition, She has identified new blood biomarkers vital for Alzheimer's disease detection in the clinical setting. Biomarkers identification can bring us a step closer to effectively screen and track disease including cancer.


Alumni:
Trevor Cunningham
Roy Feng, M.D.
Sara Moradi Tuchayi, M.D., M.P.H.
Aeden Ghebreselassie, MSN, NP-C

Research Projects

The field of cancer immunology has made substantial advances in recent years by deciphering the role of the tumor infiltrating CD8+ cytotoxic T lymphocytes (CTLs) in attacking cancer cells, which have led to promising new cancer immunotherapeutics. The current immunotherapeutic approaches, however, are largely designed to boost the anti-tumor immune response that has already formed against late-stage metastatic cancers. Therefore, the current cancer immunotherapies like immune checkpoint blockade, which rely on a pre-existing CTL infiltrate in the tumor for their effects, are proven ineffective to treat cancers that frequently lack a significant anti-tumor immune infiltrate, especially during the early in-situ phases of their development. In order to expand the potential of cancer immunotherapy, our laboratory studies the pathways that lead to immune system activation against early phases of cancer development. Devising a mechanism to activate the immune system against early-stage cancers has clear immunopreventive implications by directly blocking the cancer promotion and immunotherapeutic benefits by potentiating the immunity against late disease.

 

CD4 T cell mediated immunity against breast carcinogenesis
CD4+ T cell-mediated immunity against breast cancer development


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

(1) Mechanisms of T cell activation against cancer. 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 natural killer (NK) cell recruitment and activation against cancer. NK cells are known for their potent anti-tumor properties. However, their role in controlling the cancer development in vivo remains unclear. 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. Although immune cells can mount anti-tumor immunity against cancer, they are also implicated in promoting cancer development under certain conditions. Chronic inflammation is one of the conditions that 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.

Research Positions

Postdoctoral Research Fellow position is available for a highly motivated individual with expertise in immunology, cancer biology and genomics. Expertise in biochemical, immunological and mice experimentations are required for this position.

Interested candidates should send their information including CV and the name of 2-3 references to Dr. Shawn Demehri: sdemehri1@mgh.harvard.edu

Select Publications

For the full list of publications from the Demehri lab, please visit PubMed here.

Select publications:

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.

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.

Demehri, S., Cunningham, T.J., Hurst, E.A., Schaffer, A., Sheinbein, D.M., and Yokoyama, W.M. Chronic allergic contact dermatitis promotes skin cancer. J Clin Invest 2014; 124(11): 5037-41.

Demehri, S., Turkoz, A., Manivasagam, S., Yockey, L.J., Turkoz, M., and Kopan, R. Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin. Cancer Cell 2012; 22(4): 494-505.

Demehri, S., Turkoz, A., and Kopan, R. Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironment. Cancer Cell 2009; 16(1): 55-66.

Demehri, S., Morimoto, M., Holtzman, M.J., and Kopan, R. Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma. PLoS Biol 2009; 7(5): e1000067.

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. Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity. PLoS Biol 2008; 6(5): e123.

Contact

Our laboratory is located at the MGH-Charlestown Navy Yard, a historic neighborhood in Boston!

Mailing Address:

Demehri Lab
Cutaneous Biology Research Center
Building 149 13th Street, 3rd floor
Charlestown MA 02129
Phone: 617-724-8128
Email: sdemehri1@mgh.harvard.edu

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