Demehri Lab

Research Summary

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.

Research Projects

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:

1. Mechanisms of CD4+ T cell activation against cancer. Our laboratory studies the mechanism of epithelium-derived alarmins in evoking tumor suppression. Currently, our team investigates the detailed mechanism of anti-tumor function of alarmin cytokines against solid cancers and examines their application in treating pre-cancerous skin and breast 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 cancer development in vivo remains unclear. Our laboratory utilizes an NK cell-specific activating ligand 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 to block cancer promotion and progression.
3. The impact of commensal viruses-immune system interplay on the homeostasis of the organs exposed to environmental carcinogens. We aim to determine how the immune system's control of commensal virome regulates the homeostasis of the virus-colonized tissues. Through this effort, we aim to realize the beneficial functions of commensal virome for the prevention and treatment of cancer and other chronic diseases that affect humans.
4. Mechanisms of cancer promotion by the immune system. Although immune cells can mount anti-tumor immunity against cancer, they are also implicated in promoting cancer development in chronic inflammation. Our laboratory studies the initiating mechanisms of cancer-prone chronic inflammation development in the skin, pancreas, colon and liver, which are the major organs affected by chronic inflammation and its cancer sequela.

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

Publications

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.

Our Researchers

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

 

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.

 

Rikke Louise Christensen, M.Sc.

Graduate Student

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.

 

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 Hojanazarova

Research Technician

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.

 

Emanuela Marchese, Ph.D.

Postdoctoral Fellow

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.

 

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.

 

Valeria Oliver-García

Medical Student

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.

 

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.

 

Grace Seifu

Undergraduate Student

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.

 

 

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.

 

Ryota Tanaka, M.D., Ph.D.

Postdoctoral Fellow

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.

 

Kathryn Trerice

Undergraduate 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.

 

Eray Yihui Zhou, M.D.

Graduate Student

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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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
• Domitille Peigney
   After the Demehri Lab: Master’s student in Biology and Health, École Normale Supérieure Paris-Saclay, Université Paris-Saclay, France
• Quan Pham
   After the Demehri Lab: Immunology PhD student at the Rockefeller University
• 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
• Sabrina Smith
   After the Demehri Lab: Medical Student at the University of Central Florida
• 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