Novel immunotherapy mechanism suppresses breast cancer development
CD4+ T helper 2 cells force breast cancer cells to revert to benign breast gland cells.
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Contact Information
Cutaneous Biology Research Center
149 13th Street, 3rd floor
Charlestown,
MA
02129
Phone: 617-724-8128
Email: sdemehri1@mgh.harvard.edu
Shawn Demehri, M.D., Ph.D.
Associate Professor of Dermatology
Massachusetts General Hospital Cancer Center
Harvard Medical School
Program Affiliations
Center for Cancer Research
The focus of the Demehri laboratory is to determine the immune system's role in maintaining the homeostasis of tissues and regulating the early stages of cancer development. The research in the Demehri laboratory aims to harness the beneficial functions of the immune system to promote health and prevent cancer. To date, several cancer immunotherapies have been developed with proven efficacy against late-stage cancers; however, the immune system's role in controlling the early development of cancer remains uncertain. The research in the Demehri laboratory elucidates the immune mechanisms that drive an immune activation sufficient to prevent cancer formation from pre-cancerous lesions. This approach raises an excellent opportunity to discover novel immune pathways that can be leveraged in cancer prevention and therapy.
To realize the potential of cancer immunoprevention, our laboratory studies the pathways that lead to immune system activation against early phases of malignant transformation. Devising a mechanism to activate the immune system against pre-cancers and early-stage cancers has clear preventive implications by directly blocking cancer development and recurrence. Our research aims to improve care for a large population of patients with hereditary cancer syndromes, exposure to carcinogens, pre-cancerous lesions, and early invasive cancers. In addition, our discoveries will have immunotherapeutic benefits by potentiating 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 aging-associated 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.
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.
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
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.
B.Sc.: Biology, University of Copenhagen, Denmark
M.Sc.: Human Biology, University of Copenhagen, Denmark
Ph.D.: Clinical Cancer Research, University of Copenhagen, Denmark (degree in progress)
Rikke received her master’s degree in Human Biology from University of Copenhagen. After graduation she worked in biotech as a Scientist, where she did pre-clinical research investigating tumor and immune responses to immune-modulating cancer therapies. Currently she is completing her Ph.D. training at Bispebjerg University Hospital, Copenhagen, Denmark. In her Ph.D. studies, Rikke is investigating local targeted immune therapeutic treatment strategies for squamous cell carcinoma. In the Demehri lab, Rikke is studying the immune response in the skin and skin cancer following treatment with various energy-based dermatological devices.
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.
B.S.: Biology, Waldorf University
Jennet has graduated from Waldorf University, Iowa with a B.S. in Biology. Jennet studied nonsyndromic 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.
B.S.: Biotechnology for Health, University of Naples Federico II, Italy
M.S.: Biology, University of Naples Federico II, Italy
Ph.D.: Medical Clinical and Experimental Science, University of Campania “L.Vanvitelli”, Italy
Emanuela received her Ph.D. in 2021 studying kidney disease pathophysiology in Bardet-Biedl Syndrome. She has also been involved in several skin biology projects and has led efforts to develop proteomics- and metabolomics-based platforms. After completed her Ph.D. training, Emanuela was awarded the AICF’s postdoctoral fellowship to perform her training in the Demehri lab. Her current work is focused on the role of the immune system in regulating the early stages of cancer development in skin and breast cancer. In addition, she is studying the immunology of transition zones to determine the mechanisms of disease susceptibilities associated with these epithelial sites.
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.
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.
B.S.: Biology, University of Puerto Rico, Mayagüez Campus
M.D.: Ponce Health Sciences University School of Medicine (Degree in progress)
Valeria is currently pursuing a medical doctorate degree at Ponce Health Sciences University in Puerto Rico. She received a B.S. degree in Biology from University of Puerto Rico, Mayagüez Campus. Her work in the Demehri Lab will focus on investigating the mechanism of topical immunotherapy for skin cancer prevention and treatment. In the upcoming years, Valeria aims to expand her expertise in translational dermatological research.
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.
Grace is an undergraduate at Harvard College pursing a B.A. degree in Integrative Biology on the Premed track. She is working with the members of our lab to understand the immunological responses in regulating breast cancer development while expanding both her knowledge of the field and her skills as a researcher.
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.
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.
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.
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.
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.
B.M.: Yuanpei College, Peking University, China
M.D.: Health Science Centre, Peking University, China
M.MSc.: Clinical Investigation, Harvard Medical School (Degree in progress)
Eray is currently a master's student at Harvard Medical School. He graduated from a dermatology residency at Beijing Tsinghua Changgung Hospital, Tsinghua University in 2020. He focuses his research on the genetic backgrounds of cutaneous malignancies and genodermatoses. In the Demehri Lab, Eray is investigating the alteration of commensal skin virome and its association with cutaneous malignancies in the immunosuppressed population.
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This helped lead to new knowledge and breakthrough therapies.
CD4+ T helper 2 cells force breast cancer cells to revert to benign breast gland cells.
Scientists discover that certain proteins surrounding organs and tissues switch off natural killer cells’ “killer” function. Blocking these interactions could re-activate the cells.
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.
Populations at high risk of melanoma could particularly benefit from an approach that harnesses the immune powers of CD4+ T cells.
The molecule, interleukin-33, activates signals in a cell’s nucleus to promote abnormal growth.