A laboratory focusing of the glyco-pathological basis of inflammation and cancer
The Dimitroff Laboratory is led by principal investigator, Charles J. Dimitroff, Ph.D., who is an Assistant Professor of Dermatology at Brigham and Women’s Hospital, Harvard Medical School. The Laboratory is located on the 6th floor of the Harvard Institutes of Medicine. Dr. Dimitroff received his Ph.D. in 1999 from Roswell Park Cancer Institute, State University of New York at Buffalo in cancer pharmacology and cancer metastasis. He subsequently trained as a post-doctoral fellow with Robert Sackstein, M.D., Ph.D. in the Department of Dermatology at Brigham and Women’s Hospital (1999-2003) and researched carbohydrate-dependent adhesion processes relating to migration of white blood (immune) cells to bone and skin. These educational experiences have led to his specialized expertise in the glycobiology of cancer metastasis and inflammation. The overall goal of the Dimitroff Laboratory is to elucidate the critical carbohydrate determinants on the surfaces of tumor/immune cells that confer or alter their fate and function.
Dr. Dimitroff and his team of postdoctoral fellows, research technicians and students are currently involved in studies that help illuminate 1.) how immune cells (T cells) respond to tumor-derived factors, which characteristically bind carbohydrates on the T cell surface, and limit their tumor-killing function and 2.) how cell surface glycans on malignant melanocytes can be used to predict tumorigenicity and metastatic progression.
The following research projects in The Dimitroff Laboratory are funded by grants from the National Institutes of Health, Cancer Research Institute, American Cancer Society and Brigham and Women’s Hospital – Brigham Research Institute.
Project 1: Analysis of Cell Surface Glycans in Melanoma Malignancy & Metastasis
The major goal in this project is to characterize cell surface glycans and their lectin-binding partners on normal and malignant melanocytes and determine whether identified lectin-glycan binding pairs functionally relate to the malignant behavior and metastatic activity of melanoma cells. We hope that this work will result in a better understanding of melanoma development and perhaps, new treatments that target melanoma progression.
Project 2: Characterization of Lectin-binding Glycans on Normal & Malignant Melanocytes
The major goal of this project is identity distinct glycans on the surface of melanoma cells that are distinguishable from those present on normal or non-threatening dysplastic melanocytes. Our hope that this disparate expression pattern can be exploited as a biomarker method in the context of melanoma diagnosis and metastasis prediction.
Project 3: Studying Galectin-1 – Galectin-1 Ligand Interactions in T cell Immunity
The major goal of this project is to study galectin-1 effects on anti-tumor T cells and elucidate the downstream factors that limit their tumor-killing function upon galectin-1-binding. We hope that this work will unveil new galectin-1-dependent effects that can be targeted to reinvigorate T cell function.
Project 4: Exploring Identity & Function of Lectin-binding Glycans in Squamous Cell Carcinoma
The major goal of this project is to identify and characterize the lectin-binding partners that transmit growth-regulatory activity to normal and malignant stratified epithelia. Our hope is that this work will reveal lectin-glycan binding pairs that will induce growth cessation or potentiating activity, providing new targets for anti-cancer therapy.
Project 5: Identifying & Characterizing Lectin-binding Glycans on Neutrophils
The major goal of this project is to identify and characterize lectin-binding glycans on neutrophils that help regulate their expansion and function in inflammation Our hope is that this work will result in a better understanding of how neutrophilic glycans can be targeted to help neutralize their inflammatory activity.
Project 6: Analysis of Lectin-binding Glycans on Tumor-Infiltrating T cells in Melanoma.
The major goal of this project is to identify and correlate the presence and level of distinct lectin-binding glycans on effector T cells infiltrating human melanomas with the clinical outcome of patients. We hope that this retrospective analysis will reveal why potential T cell glycan structures can serve as predictors of melanoma progression.