Krantz Family Center for Cancer Research
Cutaneous Biology Research Center
149 13th Street, 3rd floor
Charlestown,
MA
02129
Phone: 617-724-8128
Email: sdemehri1@mgh.harvard.edu
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 prevention and therapy.
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 earlystage 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, our laboratory studies the role of alarmins, damage-associated molecular patterns (DAMPs)/stress signals, commensal viruses, carcinogens, and agingassociated factors in regulating early cancer development. The major areas of research in our laboratory are:
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
For the full list of publications from the Demehri lab, please visit PubMed here.
Park, J.H., Mortaja, M., Son, H.G., Zhao, X., Sloat, L.M., Azin, M., Wang, J., Collier, M.R., Tummala, K.S., Mandinova, A., Bardeesy, N., Semenov, Y.R., Mino-Kenudson, M., Demehri, S., Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression. Nature Communications. 2024 May 30;15(1):4099. doi: 10.1038/s41467-024-48441-8. PMID: 38816352.
Huang, M., Xia, Y., Li, K., Shao, F., Feng, Z., Li, T., Azin, M., and Demehri, S., Carcinogen exposure enhances cancer immunogenicity by blocking the development of an immunosuppressive tumor microenvironment. J Clin Invest. 2023 Oct 16;133(20). PMID: 37843274.
Hasegawa, T., Oka, T., Son, H. G., Oliver-García, V. S., Azin, M., Eisenhaure, T. M., Lieb, D.J., Hacohen, N., Demehri, S., Cytotoxic CD4+ T cells eliminate senescent cells by targeting cytomegalovirus antigen. Cell. 2023 Mar 30;186(7):1417-1431.e20. PMID: 37001502.
Boieri, M., Malishkevich, A., Guennoun, R., Marchese, E., Kroon, S., Trerice, K. E., Awad, M., Park, J. H., Iyer, S., Kreuzer, J., Haas, W., Rivera, M. N., Demehri, S., CD4+ T helper 2 cells suppress breast cancer by inducing terminal differentiation. J Exp Med. 2022 Jul 4;219(7) PMID: 35657353.
Bunting, M.D., Vyas, M., Requesens, M., Langenbucher, A., Schiferle, E. B., Manguso, R. T., Lawrence, M. S., Demehri, S., Extracellular matrix proteins regulate NK cell function in peripheral tissues. Science Advances. 2022 Mar 18;8(11):eabk3327. PMCID: PMC8926340.
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.
Shawn Demehri, M.D., Ph.D.Associate 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
Kentaro Awaji, M.D., Ph.D.M.D.: The University of Tokyo, Japan
Ph.D.: Dermatology, The University of Tokyo, Japan
Kentaro has worked as a clinician in Japan for ten years in the field of internal medicine and dermatology. He received his Ph.D. degree in Dermatological sciences in 2022, studying the role of Fli1 deficiency in B cells on the development of systemic sclerosis. He specializes in connective tissue diseases and skin cancers and is well-versed in autoimmunity, fibrosis, and cancer management. In the Demehri Lab, Kentaro is studying the contribution of fibrosis induced by aberrant immune cell activation in the development of UV-induced skin cancers.
Marjan Azin, M.D.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.
Danielle ConradB.A.: Anthropology, University of Cincinnati
B.A.: Archaeology, University of Cincinnati
B.S.: Biological Science, University of Rhode Island
Danielle joined Demehri lab as a Biological Science graduate from URI. With a background in healthcare, she is assisting with the clinical aspects of the laboratory research and working with other lab members on their research projects. She is interested in studying the role that genetics play in cancer development and treatment.
Magda DawitMagda is an undergraduate student at Northeastern University pursuing a B.S. degree in Health Science on the Premed track. She is working with other lab members to determine the role of polyomaviruses on immune response in cancer and inflammatory diseases while expanding her knowledge of the field and her research skills.
Hiroshi Higuchi, Ph.D.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.
Satoshi HoribaB.S.: Bioscience, Tokyo University of Pharmacy and Life Sciences, Japan
M.S.: Frontier Sciences, University of Tokyo, Japan
Satoshi received his M.S. degree in Frontier Sciences from the University of Tokyo. After graduation, he joined the Shiseido company in Japan, where he studied the collagen function in skin aging. He also worked on analyzing the effect of macrophages, especially the balance of M1/ M2 macrophages, on skin aging. In the Demehri lab, Satoshi studies the immune system's role in regulating skin aging.
Unser JaffryB.S.: Biology, Michigan State University
Unser graduated from Michigan State University in 2024, earning a bachelor’s degree in biology on a premed track. During his undergraduate studies, he conducted research on chemotherapy induced neuropathic pain, as well as cholesterol crystals. He also gained experience in clinical research while working during his undergraduate years. In the Demehri lab, Unser collaborates with lab members to explore the role of polyomaviruses in the immune response related to cancer and inflammatory diseases while further developing his research skills.
Suhani JainSuhani is studying Biology and Business Administration at Northeastern University. She has previously conducted research related to Alport's syndrome, diabetic wound healing, and cutaneous leishmaniasis. Currently, in the Demehri lab, she is working on a project focusing on Xeroderma Pigmentosum (XP), specifically investigating the XPC gene. During her time in the lab, Suhani aims to deepen her understanding of dermatological diseases and contribute to the development of better preventive and therapeutic approaches in the field.
Truelian LeeB.A.: Chemistry and English, Harvard College
M.D.: Harvard Medical School (in progress)
Truelian graduated from Harvard College in 2021 and is currently a medical student at Harvard Medical School pursuing an M.D. degree in the Pathways program. She previously conducted research on Shigella pathogenesis at MGH/HMS. Her work in the Demehri Lab is focused on the application of thymic stromal lymphopoietin cytokine induction for precancerous skin lesions and invasive skin cancer treatment.
Alex McGarryAlex is pursuing a B.S. in Biology at Boston University. He is participating in projects involving NK cell activation in solid tumors via extracellular matrix proteins and the role of TSLP in postnatal breast gland differentiation. Through working in the lab, he continues to broaden his understanding of research regarding immunology as well as develop wet skills within the lab.
Ethan MillardB.S.: Cell Biology and Neuroscience, Montana State University
Ethan participated in undergraduate research studying early embryonic development in Xenopus and zebrafish, specifically focusing on the role Aquaporins play in mediating convergent extension, an essential process for the formation of the nervous system. He interned at the Buck Institute in the Verdin lab, where he studied CD38’s role on NAD+ decline and aging within the brain. In the Demehri lab, Ethan will work with other lab members to help uncover the role T cells play in breast cancer formation and prevention.
Rosanna Monetta, Ph.D.B.S.: Biological Sciences, University of Naples Federico II, Italy
M.S.: Molecular Biology, University of Naples Federico II, Italy
Ph.D.: Department of Life, Health and Environmental Sciences, University of L'Aquila, Italy
Rosanna earned her Ph.D. in 2022, specializing in genodermatoses and cardiovascular diseases associated with cell adhesion defects. Her research focused on identifying the molecular bases of these diseases and characterizing the underlying altered pathways. Following her Ph.D., Rosanna undertook a postdoctoral position at the Istituto Dermopatico dell'Immacolata-Fondazione Luigi Maria Monti-IRCCS in Italy, where she investigated a non-competitive antagonist of the TrkB receptor, hypothesized to inhibit invasion in squamous cell carcinoma. Additionally, she utilized 3D printing technology to develop more physiologically accurate skin models and recreate pathophysiological environments for studying squamous cell carcinoma and basal cell carcinoma. Currently, in the Demehri Lab, Rosanna is working on projects aiming to investigate the role of NK receptors in the regulation of breast cancer and melanoma.
Tomonori Oka, M.D., Ph.D.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.
Heehwa (Grace) Son, Ph.D.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.
Ryota Tanaka, M.D., Ph.D.M.D.: University of Tsukuba, Japan
Ph.D.: Dermatology, University of Tsukuba, Japan
Ryota worked as a clinician in Japan, trained both as a dermatologist and an oncologist. In 2020, he received his Ph.D. degree demonstrating the pathophysiology of anti-programmed cell death (PD)-1 antibody-induced psoriasiform dermatitis. He also has shown differential involvement of PD-ligands in skin immune responses. In the Demehri Lab, Ryota is working on a project to elucidate the role of the immune system in suppressing the carcinogenesis of epithelial tissues in which mutated DNA is accumulated.
Olivia TuckerB.S.: Animal Science, Cornell University
Olivia graduated from Cornell University in 2023 receiving a bachelor’s degree in animal science on the Pre-vet track. During her undergraduate career, she conducted research to study single nucleotide polymorphisms in genes affecting reproductive health and milk production. She also conducted research at Cornell’s College of Veterinary Medicine to study mechanisms of regeneration in stem cells. In the Demehri lab, Olivia is working with other lab members to study the role of viral immunology in cancer prevention.
Dongyao Wang, Ph.D.B.Sc.: Preventive medicine, Norman Bethune Health Science Center, Jilin University, China
Ph.D.: Immunology, University of Science and Technology of China, China
Dongyao received his PhD degree and completed postdoctoral work in immunology from University of Science and Technology of China (USTC). His work demonstrated that pharmacologic inhibition of GARP-mediated active TGF-β1 signaling could restore NK cell-mediated graft-versus-leukemia (GVL) activity. In addition, he demonstrated that sequential low-dose IL-2 therapy increased the frequency and function of HBV-specific CD8+ T cells, which contributed to HBeAg seroconversion, among the non-responder chronic hepatitis B patients after IFN-α therapy. Furthermore, he found that the inhibition of IL-11-STAT3 signaling could significantly suppress postsurgical recurrence of liver cancer. In the Demehri Lab, Dongyao studies the role of NK cells and chronic inflammation in liver cancer.
Xiaoyu (Charlene) WangM.D. and Ph.D.: Tsinghua University, Beijing, China (in progress)
Charlene is a medical student pursuing her M.D./Ph.D. in the physician-scientist program at Tsinghua University. With a passion for bridging clinical practice and research, she previously explored 3D bioprinting techniques to create vascularized tumor models, shedding light on tumor-vascular interactions and advancing patient-specific drug screening. Her current research in Demehri lab delves into the role of commensal viruses in maintaining skin homeostasis.
Yun Xia, Ph.D.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.
Connie YuB.S.: Biopsychology, Tufts University
Connie conducted undergraduate research at UTHealth Houston to study post-stroke neuroinflammatory signaling pathways and gut bacterial dysbiosis on stroke outcomes. She also conducted research at the Broad Institute studying the cellular phenotypes linked to human genetic variants associated with neuropsychiatric disorders. In the Demehri lab, she is working to understand the role of the immune system in regulating breast cancer development.
Amy ZengAmy is an undergraduate at Tufts University, studying Biology and Life Chemistry on the Pre-med track. She previously interned at a company in China, which focused on advancing CAR-T cell therapies. In the Demehri lab, she is working with other lab members to explore the role of papillomavirus on immune response activation against cancer. During her time in the lab, she hopes to expand her research skills and explore the possibilities of early cancer prevention.
Can (Nora) Zhou, M.D.M.D.: Clinical Medicine, Nanjing Medical University, China
Ph.D.: Dermatology, Zhejiang University, China (in progress)
Nora received her M.D. degree in 2021 and is now pursuing a Ph.D. degree in dermatology at Zhejiang University, where she investigates the pathogenic mechanisms of skin diseases related to human papillomavirus infection, focusing primarily on the effects of the HPV E7 protein on mitochondrial autophagy and cell proliferation. At the Demehri Lab, Nora is expanding her studies to explore how interactions between skin commensal viruses and the immune system influence the development of skin cancer and other dermatological conditions.
Xutu Zhao, M.D.B.M.: Zhongshan Medical School, Sun Yat-sen University, China
M.D.: Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China
Xutu received his M.D. from Sun Yat-sen University in 2022. He worked as a clinician and focused on treating malignant breast tumors at the First Affiliated Hospital of Sun Yat-sen University in China. In the Demehri lab, his work will focus on investigating the role of the immune system in regulating the development of breast cancer.
