Researchers from Massachusetts General Hospital (MGH) have discovered a biological mechanism that transforms cells exposed to carcinogens from environmental factors like smoking and ultraviolet light into immunogenic cells that can be harnessed therapeutically to fight treatment-resistant cancers.
Cutaneous Biology Research Center
149 13th Street, 3rd floor
Charlestown, MA 02129
Shawn Demehri, M.D., Ph.D.
Associate Professor of Dermatology
Massachusetts General Hospital Cancer Center
Harvard Medical School
Center for Cancer Research
Explore the 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 prevention and treatment. 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 the Demehri 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.
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.
To pursue this goal, Demehri laboratory studies the role of alarmins, damage-associated molecular patterns (DAMPs)/stress signals, commensal viruses, and carcinogen and aging associated factors in regulating early cancer development. The Demehri laboratory is currently focused on three areas of research:
- Mechanisms of CD4+ T cell activation against cancer. Our laboratory has studied the mechanism of thymic stromal lymphopoietin (TSLP) in evoking tumor suppression. 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 and breast lesions in patients.
- 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.
- 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 and colorectal cancer development as ideal cancer models 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 and colorectal cancer development in the context inflammatory bowel disease.
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: email@example.com
Schiferle, E. B., Cheon, S. Y., Ham, S., Son, H. G., Messerschmidt, J. L., Lawrence, D. P., Cohen, J. V., Flaherty, K. T., Moon, J. J., Lian, C. G., Sullivan, R. J., Demehri, S., Rejection of benign melanocytic nevi by nevus-resident CD4(+) T cells. Science Advances 7, (2021).
Li, K., Li, T., Feng, Z., Huang, M., Wei, L., Yan, Z., Long, M., Hu, Q., Wang, J., Liu, S., Sgroi, D. C., Demehri, S., CD8(+) T cell immunity blocks the metastasis of carcinogen-exposed breast cancer. Science Advances 7, (2021).
Park, J. H., Ameri, A. H., Dempsey, K. E., Conrad, D. N., Kem, M., Mino-Kenudson, M., Demehri, S., Nuclear IL-33/SMAD signaling axis promotes cancer development in chronic inflammation. EMBO J 40, (2021).
Strickley JD, Messerschmidt JL, Awad ME, Li T, Hasegawa T, Ha DT, Nabeta HW, Bevins PA, Ngo KH, Asgari MM, Nazarian RM, Neel VA, Jenson AB, Joh J, and Demehri S. Immunity to commensal papillomaviruses protects against skin cancer. Nature. 2019 Nov;575(7783):519-522. PMID: 31666702.
Rosenberg AR, Tabacchi M, Ngo KH, Wallendorf M, Rosman IS, Cornelius LA, Demehri S. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight. 2019;4(6). Epub 2019/03/22. doi: 10.1172/jci.insight.125476.
Ameri AH, Moradi Tuchayi S, Zaalberg A, Park JH, Ngo KH, Li T, Lopez E, Colonna M, Lee RT, Mino-Kenudson M, Demehri S. IL-33/regulatory T cell axis triggers the development of a tumor-promoting immune environment in chronic inflammation. Proceedings of the National Academy of Sciences of the United States of America. 2019. Epub 2019/01/31. doi: 10.1073/pnas.1815016116.
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., 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.
Shawn Demehri, M.D., Ph.D.
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
Marjan Azin, M.D.Research Fellow
M.D.: Tehran University of Medical Sciences (TUMS), Iran
Marjan received her medical diploma from Tehran University of Medical Science in 2015. She has directed research projects at her hospital, studying the prognostic significance of Matrix Metalloproteinase-7 (MMP-7) in colorectal cancer survival, the effect of exercise program in serum Vaspin level in diabetic patients, and studying sleep disorders in patients with neuropathic pain. At Children Medical Center, she the immune dysregulation in children with allergic skin diseases. Marjan is studying the role of alarmins in suppressing cancer development in patients with breast cancer cutaneous metastasis in the Demehri lab.
Michael BittnerResearch Technician
B.S.: Biology, Providence College
Michael has recently received his Bachelor of Arts in Biology at Providence College. His previous research experience has been focused on understanding the role of Bax Inhibitor in the progression of cancer in yeast cells and C. elegans. He hopes to obtain a Ph.D. in the upcoming years and pursue a career in oncology research. In the Demehri lab, Michael is studying the immune environment of barrier organs in mice and humans.
Hiroshi Higuchi, Ph.D.Postdoctoral Fellow
B.S., M.S. & Ph.D.: Bioengineering, Nagoya University, Japan
Hiroshi received his Ph.D. in 2016 studying the role of sialic acid-binding lectin Siglecs in the inflammatory regulation in macrophages. He also worked on the analysis of macrophage function in the development of Epstein-Barr virus (EBV)-associated B-cell lymphoma as a Postdoctoral Fellow in Japan. In this study, he demonstrated the importance of extracellular vesicles as a novel communicator between tumor cells and macrophages. His current work in the Demehri Lab is focused on the innate immune function of epithelial cells in response to papillomavirus infection.
Jennet HojanazarovaResearch Technician
B.S.: Biology, Waldorf University
Jennet has graduated from Waldorf University, Iowa with a B.S. in Biology. Jennet studied non-syndromic orofacial clefts by measuring enhancer activity of disease-associated SNPs at the University of Iowa. She also measured the effects of IP3Rs and ALG-2 on the ER-to-Golgi transport at the University of Montana. In the Demehri lab, Jennet is studying the role of CD4+ T cells in regulating adenocarcinoma of the lung. She is also assisting in the study of commensal viruses to determine their impact on innate immunity.
Monica JaffeeUndergraduate Student
Monica is a current undergraduate at Northeastern University pursuing a B.S. degree in Biological Sciences and a B.A. degree in Philosophy of Ethics. Her background includes lab work in biological contamination as well as in bacterial cell cultures. In the Demehri lab, Monica is studying the mechanism of NK cell effects in cancer immunology.
Mahsa Mortaja, M.D.Research Fellow
M.D.: Tehran University of Medical Sciences (TUMS), Iran
Mahsa received her medical doctorate degree from Tehran University of Medical Science in 2018. After Graduation she has worked at Cancer Research Center of Iran, studying cancer immunology and pathology. Her previous research experience has been focused on understanding the role of the immune system in prevention of head and neck squamous cell carcinoma. She investigated the association between allergic disorders and risk of head and neck mucosal squamous cell carcinoma. In addition, she studied the role of cancer associated fibroblasts in tumor growth, invasion, survival and metastasis in oral squamous cell carcinoma. In the Demehri lab, Mahsa is studying the mechanism of chronic inflammation-induced cancer development.
Tomonori Oka, M.D., Ph.D.Postdoctoral Fellow
M.D.: University of Tokyo, Japan
Ph.D.: Dermatology, University of Tokyo, Japan
Tomonori received his Ph.D. degree in Dermatological sciences in 2018 studying the role of CXCL17 in psoriasis. During his clinical work as a dermatologist, he has focused on cutaneous T-cell lymphoma and atopic dermatitis. In the Demehri Lab, Tomonori is studying the mechanisms of skin cancer immunoprevention.
Jongho Park, Ph.D.Postdoctoral Fellow
B.Sc.: Computer Science Engineering and Biomedical Science, Pusan National University, Pusan, Korea
M.S. & Ph.D.: Biological Science, Seoul National University, Seoul, Korea
Jongho received his Ph.D. in biological science in 2016 studying protein modifications, such as ubiquitination and SUMOylation. He demonstrated a novel post-translational modification of tumor suppressor DBC1 and p53 induced by DNA damage, which can lead to upregulation of their suppressor activity. During his work in industry, Jongho has investigated the mechanism of rare genetic diseases, such as hemophilia, for the development of new therapeutic antibodies. His current work in the Demehri laboratory is focused on molecular signaling pathway within keratinocyte that can govern skin cancer immunity.
Quan PhamGraduate Student
B.S.: Biochemistry and Molecular Biology, University of California, Irvine
M.S.: Immunology, Harvard Medical School (Degree in progress)
Quan is currently a master’s student at Harvard Medical School. He received his B.S. degree in Biochemistry and Molecular Biology from UC Irvine. After graduation, he joined the Melton lab at Harvard University, where he studied the role of the AKT/PI3K/mTOR pathway in pancreatic development and stem cell-derived beta-cell differentiation. In the Demehri lab, Quan is investigating the mechanism in which CD4+ T cells regulate breast cancer development. In the upcoming years, he hopes to pursue a PhD degree in cancer immunology.
Heehwa (Grace) Son, Ph.D.Postdoctoral Fellow
B.Sc.: Biotechnology, Konkuk University, Seoul, South Korea
M.S. & Ph.D.: Molecular biology and Genetics, Pohang University of Science and Technology (POSTECH), Pohang, South Korea
Heehwa received her PhD in molecular biology and genetics in 2018 studying the roles of RNA quality controls in aging process using a model organism, C. elegans. She found that one of the RNA quality control mechanisms, nonsense-mediated mRNA decay, has protective effects against aging. She also worked on investigating the roles of chaperones in lifespan regulation. In the Demehri lab, she is working on the cellular impacts of immunotherapies on early stage epithelial cancers.
Kathryn TrericeUndergraduate Student
Katie is an undergraduate at Harvard College pursing a B.S. degree in Molecular and Cellular Biology. She is working with other lab members on their research projects while expanding both her knowledge of the field and her skills. Katie has joined our efforts to understand the role of CD4+ T cells in regulating lung cancer development.
Maulik Vyas, Ph.D.Postdoctoral Fellow
B.Sc. (Honors): Biomedical Science, University of Central Lancashire, UK
M.Sc.: Cancer Immunology & Biotechnology, University of Nottingham, UK
Ph.D.: Cancer Immunotherapy, University of Cologne, Germany
Maulik received his PhD in the field of Cancer Immunotherapy in 2016 where his work focused on designing and developing recombinant trispecific immunoligands (“triplebodies”) to harness NK cells against leukemia. His triplebodies showed successful retargeting of NKG2D-dependent NK cell response against primary leukemia cells in both, allogeneic and autologous settings. Significant in vivo potency of the triplebody was observed in immunodeficient (NSG) mouse model which further suggested its therapeutic potential. Maulik then worked as a postdoctoral fellow at Philipps University Marburg, Germany to study the NK cell suppression in response to soluble NKG2D-ligands or other yet unknown factors present within the ascites of ovarian cancer patients. His current work in the Demehri laboratory is focused on understanding how immune cells, in particular NK cells, regulate the early stages of cancer development.
Yun Xia, Ph.D.Postdoctoral Fellow
B.Sc. Biotechnology, Anhui normal University, China
M.Sc.: Immunology, Soochow University, China
Ph.D.: Immunology, Tsinghua University, China
Yun received his PhD degree in immunology from Tsinghua University in 2020. He found that mevalonate pathway inhibitors could induce strong immune responses and were suitable for vaccine adjuvants. The adjuvanticity associated with mevalonate pathway inhibition activates multiple arms of immunity, including Th1 and cytolytic T cell responses and is thus suitable for cancer immunotherapies. This discovery presented a new approach for the development of both vaccine and cancer research. In the Demehri lab, Yun focuses on studying the role of alarmins in COVID-19 response and the role of commensal viruses in immunity at epithelial sites.
Martina ZoiResearch Technician
B.S. Biological Science (Degree in Progress), Northeastern University
B.S.: Medical Laboratories, University of West Attica, Athens, Greece
Martina joined Demehri lab as a student pursuing her Bachelor of Science degree in Biological science from Northeastern University. She has previously received a B.S. degree in Medical Laboratories at the University of West Attica. Though her background is in diagnostic laboratories, she hopes to gain research experience and advance her knowledge and skills to laboratory studies that will follow while assisting research fellows with their projects by conducting research experiments. She is interested in studying genetics and its role in breast cancer in its early development.
Demehri Lab Alumni
- Amir Ameri, M.D.
After the Demehri Lab: Internal Medicine Resident at the Johns Hopkins University
- Mary Awad, M.D.
After the Demehri Lab: Dermatology Resident at University of Massachusetts School of Medicine
- Margherita Boieri, Ph.D.
After the Demehri Lab: Scientist at Zelluna Immunotherapy, Norway
- Mark Bunting, Ph.D.
After the Demehri Lab: Postdoctoral Fellow in the Genome Editing Laboratory at the University of Adelaide and South Australian Health and Medical Research Institute (SAHRMI), Australia
- Scarlett (Se Yun) Cheon
After the Demehri Lab: Medical Student at Tulane University (starting in 2023)
- Danielle Conrad
- Trevor Cunningham
After the Demehri Lab: Senior Research Technologist at St. Jude Children's Research Hospital
- Kaitlin Dempsey
After the Demehri Lab: Physician Assistant Student at Cornell University
- Roy Feng, M.D.
After the Demehri Lab: Sr. Physician at BeiGene Co., China
- Ranya Guennoun
After the Demehri Lab: MD-PhD Student at Washington University in St. Louis
- Aeden Ghebreselassie, MSN, NP-C
After the Demehri Lab: Family Nurse Practitioner, Woodbridge, Virginia
- Tatsuya Hasegawa, Ph.D.
After the Demehri Lab: Scientist at Shiseido Co., Japan
- Mei Huang, Ph.D
After the Demehri Lab: Associate Research Fellow at University of Science and Technology, China
- Sanne Kroon
After the Demehri Lab: PhD student in ETH Zurich, Inst. of Molecular Health Sciences, Netherlands
- Kaiwen Li, M.D.
After the Demehri Lab: Associate Professor in the Department of Urology at Sun Yat-sen Memorial Hospital, China
- Tiancheng Li, M.D.
After the Demehri Lab: Associate Professor and Associate Chief Physician in the Department of Otolaryngology at Peking University First Hospital, China
- Elena Lopez
After the Demehri Lab: MD/MBA Student at Northwestern Feinberg School of Medicine (starting in 2022)
- Jonathan Messerschmidt
After the Demehri Lab: MD-PhD Student at Duke University
- Sara Moradi Tuchayi, M.D., M.P.H.
After the Demehri Lab: Postdoctoral Fellow at Wellman Center, MGH
- Kenneth Ngo
After the Demehri Lab: Lead Research Associate at Dana Farber Cancer Institute
- Marta Requesens Rueda
After the Demehri Lab: PhD student in Faculty of Medical Sciences, University of Groningen (RUG), Netherlands
- Erik Schiferle
After the Demehri Lab: PhD Student at Boston University
- Bo Wang, Ph.D.
After the Demehri Lab: Associate Research Fellow at Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China
- Anniek Zaalberg
After the Demehri Lab: PhD Student at Netherlands Cancer Institute, Netherlands
- Anna Zemel, Ph.D.
After the Demehri Lab: Instructor at Ariel University, Israel
- Press Release
- Feb | 22 | 2021
The molecule, interleukin-33, activates signals in a cell’s nucleus to promote abnormal growth.