Demehri Lab

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 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 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.

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.

To pursue this goal, our 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. We investigate:

• 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.

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.

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 Oct 30;. 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.

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.

 

Our Researchers

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

 

Marjan Azin, M.D.

Research Fellow

M.D.: Tehran University of Medical Science (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 Demehri lab.

 

Margherita Boieri, Ph.D.

Postdoctoral Fellow

B.Sc.: Biotechnology, University of Turin, Italy
M.Sc.: Medical biotechnologies, Regenerative Medicine, University of Florence, Italy
Ph.D.: Immunology, University of Oslo, Norway

Margherita received her PhD in immunology studying how NK cells pre-activated in vitro with IL-12, IL-15, and IL-18 can be used as therapeutic tool to treat T-cell acute lymphoblastic leukemia in animal models. In a parallel project, she studied the contribution of the different Th population to the development of experimental acute GvHD in animal models. She plans to focus her studies into the role of CD4+ T cells and NK cells in antitumor immunity.

 

Scarlett (Se Yun) Cheon

Research Technician

B.A.: Wellesley College

Scarlett has recently received her B.A. degree in Biological Sciences from Wellesley College. She has previously worked in the Knoechel lab, a cancer epigenetic lab, at Dana Farber Cancer Institute/Boston Children’s Hospital and the Fusco lab at MGH/HMS. In the Fusco lab, she worked on identifying host factors that are required in interferon antiviral response post viral subversion points through in vitro and in vivo models for Dengue/Zika viruses. In the Demehri lab, Scarlett is studying the mechanism of NK and other immune cells activation in the skin.

 

Danielle Conrad

Research Technician (Lab Manager)

B.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 recent Biological Science graduate from URI. With a background in healthcare, she will be assisting with the clinical aspects of the laboratory research and working with other lab members on their research projects while further developing her own skills and techniques. She is interested in studying the role genetics play in cancer development and treatment.

 

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.

 

Ranya Guennoun

Research Technician

B.S.: Microbiology,Oregon State University

Ranya has recently received her Bachelor of Science in Microbiology with a Chemistry minor and a Pre-Medical Option at Oregon State University. Her previous research experience has been focused on understanding the role that Vitamin D plays in the regulation of the human antimicrobial peptide Cathelicidin. She hopes to attend Medical School in the next upcoming years and pursue a career in Oncology. At the Demehri Laboratory, she is studying the role of CD4+ Tcells in regulating lung cancer development.

 

Thinh Dat (Andy) Ha

Research Technician

B.S.: Biology, Western Kentucky University
M.S.: Chemistry, Western Kentucky University

Andy received his Master of Science degree in Chemistry from Western Kentucky University studying engineered zinc finger proteins to develop new sensing technology for double-stranded DNA. He developed different non-PCR detection systems for pathogenic DNA sequence such stx2 gene encoding for shiga toxin presence in E. coli O157:H7, as well as tetracycline resistance genes for the detection of antibiotic resistant bacteria. Andy is currently conducting research on the interplay of mouse papillomavirus, host immunity and cancer under the supervision of Dr. Joongho Joh at University of Louisville James Graham Brown Cancer Center.

 

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.

 

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 Demehri Lab is focused on the innate immune function of epithelial cells in response to papillomavirus infection.

 

Mei Huang, Ph.D.

Research Fellow

B.S.: Biological Science, Anhui University, China
M.S. & Ph.D.: Cellular Biology, University of Science and Technology of China, China

Mei received her PhD degree in cellular biology from USTC. Her project was to construct a single adenoviral vector that simultaneously expressed multiple siRNA expression cassettes and inhibited the target gene expression on mouse hepatocytes by intravenous injection into mice. The target molecules are various ligands of NKG2D, which is an innate activating receptor on NK cells, γδT cells and CD8+T cells. This intervention therapy prevents natural killer cell-mediated fulminant hepatitis in mice. At the First Affiliated Hospital of USTC, she studied the mechanism of NK cell exhaustion in human hepatocellular carcinoma. Her current work in the Demehri laboratory is focused on understanding how carcinogen exposure leads to higher tumor immunogenicity besides just increasing the neoantigen load in the tumor cells.

 

Jonathan Messerschmidt

Research Technician

B.A.: Biochemistry and Molecular Biology (Honors, Summa Cum Laude)

Jon is a recent graduate of the Biochemistry and Molecular Biology program at Boston University. He started his research career at Lankenau Institute for Medical Research studying the effects of indoleamine 2,3-dioxygenase 2 (IDO2) in the development and progression of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. At Boston University, he characterized a novel multiple cysteine cluster Toll-Like Receptor and discovered the first pathogen in a coral immunity model organism. Jon hopes to take the insight and technical skills he develops in Demehri lab onto his future career as an oncologist. In addition to treating patients, he plans to study methods of immune modulation in solid tumors to develop novel therapeutics for cancer treatment. Jon has joined the research efforts into role of chronic inflammation in cancer promotion.

 

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 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.

 

Erik Schiferle

Research Technician

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

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.

 

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 Demehri lab, she is working on the cellular impacts of immunotherapies on early stage epithelial cancers.

 

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.

 

Bo Wang, Ph.D.

Research Fellow

B.Sc.: Biological sciences, Central China Normal University, China
Ph.D.:Cell Biology, Sun Yat-sen University, China

Bo received his Ph.D. in Cell Biology in 2012, with specific training and expertise in T cell and macrophage immunobiology, Tumor-immune staging and therapy. Using tissue micro-localization platforms, Bo investigated how human tumor cells dynamically educate the infiltrating immune cells and the clinical significance of these interactions. He studied the cancer-immune cell interactions from the initial establishment of a cancer to the development of metastatic disease, with a focus on T cells and Macrophages in human bladder cancer. His current work in Demehri lab is on the role of alarmins in suppressing cancer development in patients with breast cancer and melanoma.

 

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Demehri Lab Alumni

• Amir Ameri, M.D.
• Mary Awad, M.D.
• Mark Bunting, Ph.D.
• Trevor Cunningham
• Roy Feng, M.D.
• Aeden Ghebreselassie, MSN, NP-C
• Sanne Kroon
• Kaiwen Li, M.D.
• Tiancheng Li, M.D.
• Elena Lopez
• Sara Moradi Tuchayi, M.D., M.P.H.
• Kenneth Ngo
• Marta Requesens Rueda
• Anniek Zaalberg
• Anna Zemel, Ph.D.