Immunology Faculty Member - Charles Dimitroff, PhD

Charles Dimitroff, PhD

Harvard Skin Disease Research Center
HIM Bldg. Rm. 662
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-525-5693
Fax: 617-525-5571
Email: cdimitroff@rics.bwh.harvard.edu
Visit my lab page here.



A laboratory focusing of the glyco-pathological basis of immunity, inflammation & cancer

The Dimitroff Laboratory is led by principal investigator, Charles J. Dimitroff, Ph.D., who is an Associate 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 the glycobiology of cancer. 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 and studied carbohydrate-dependent adhesion processes relating to migration of immune cells to bone and skin. These educational experiences have led to his specialized expertise in the glycobiology of adaptive immunity, inflammation and cancer.

Dr. Dimitroff has studied the nature of lectin – carbohydrate interactions and their impact in inflammation and cancer for the last 24 years. He has an expertise in glycobiology studies relating to tumor biology and adaptive immunity and is qualified to perform pre-clinical research investigating how glycome-related molecules contribute to the pathogenesis of inflammation and cancer. He conducts both in vitro and in vivo experiments designed to characterize the identity and function of lectins and their carbohydrate-binding ligands on leukocytes and cancer cells. He has published extensively on the role of lectins controlling T cell, B cell, NK cell, leukemic/hematopoietic stem cell and solid cancer cell trafficking (metastasis), adhesion, fate and/or differentiation. His experimental systems include the use of carbohydrate inhibitors, MALDI-TOF-TOF MS/MS, “home grown” selectin/ galectin-human Fc chimeras and glycosyltransferase mutant cell lines/mice as glycobiological tools to identity and characterize selectin/galectin ligands functioning in inflammation, tumorigenesis, metastasis, tumor immune evasion and lymphomagenesis. His studies include the use of native human tissues/cells as sources to isolate the relevant immune/cancer cells. These efforts are funded through NIH R-award grant mechanisms and have led to a reputation as a global leader on studies of the glycobiology of inflammation and cancer.

Dr. Dimitroff’s Laboratory is a leading training laboratory at Harvard Medical School for the next generation of immune/cancer research scientists. He serves as a Faculty Member, Harvard Immunology Ph.D. Program; Chair, BWH Dermatology Scholarship Oversight Committee; Director, BWH Dermatology Training Program; and Associate Director for Laboratory Research, BWH Dermatology.

His Research Program is currently investigating the following research areas:

Immune Research Program: His current research focus is to define the glycomic signature and function on human B cells. Using lessons from his prior studies on T cell and HSC glycobiology, he is employing a battery of glycobiological tools to interrogate cell surface glycans, glycosyltransferases and related lectin-binding partners on human B cell subsets. The goal is identify a stage-specific glycomic signature and study its functional impact on B cell fate. These findings will significantly impact our understanding of how glycobiology regulates long-lived humoral immunity, effective vaccination and B-lymphogenesis.

Cancer Research Program: He is currently exploring the glycobiology of malignant melanomas. He has obtained exciting preliminary data that the glycomic signature of melanoma cells is vastly different than most other common malignancies. The glycomics of melanoma cells are being interrogated structurally and functionally to discern whether a causal relationship drives melanoma virulence and metastasis.

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 malignant melanoma cells and determine whether identified lectin-glycan binding functionally relate to the malignant behavior and metastatic activity of melanoma cells. The hope is that this work will result in a better understanding of melanoma development and perhaps, new treatments that target melanoma progression.

Project 2: Studying Galectin Ligand Interactions and Human T cell Immunity
The major goal of this project is to identify and characterize galectin ligands on human T cells and elucidate the downstream factors that influence effector fate and function upon galectin-binding. The hope is that this work will unveil galectin-dependent effects that can be targeted to impact T cell-mediated diseases or boost anti-tumor immune responses.

Project 3: Glycomic Characterization of Human B cells
The major goal of this project is to identify and characterize glycomic features of human B cell subsets that mark their effector function or ability to differentiate/maintain effector function.

Project 4: Studies on Galectin Ligand Interactions and B cell Immunity
The major goal of this project is to identify and characterize galectin ligands on human B cells and elucidate downstream events that influence effector fate and function upon galectin-binding. The hope is that this work will unveil galectin-dependent effects that can be targeted to strategically boost vaccination approaches or to antagonize B cell-mediated diseases or B-lymphomagenesis.

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 fate and function in inflammation. The 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 Leukocytes
The major goal of this project is to identify and correlate the presence and level of distinct lectin-binding glycans on lymphoid/myeloid cells infiltrating human cancers with the clinical outcome of patients. The hope is that this analysis will reveal why distinct glycans predict cancer progression







































Last Update: 7/27/2016



Publications

Barthel SR, Wiese GK, Cho J, Opperman MJ, Hays DL, Siddiqui J, Pienta KJ, Furie B, Dimitroff CJ. Alpha 1,3 fucosyltransferases are master regulators of prostate cancer cell trafficking. Proc. Natl. Acad. Sci., 2009; 106(46):19491-6.

Cedeno-Laurent F, Barthel SR, Opperman MJ, Lee DM, Clark RA, Dimitroff CJ. Development of a nascent galectin-1 chimeric molecule for studying the role of leukocyte galectin-1 ligands and immune disease modulation,
J. Immunology, 2010;185(8):4659-72.

Barthel SR, Antonopoulos A, Cedeno-Laurent F, Schaffer L, Hernandez G, Patil SA, North SJ, Dell A, Matta KL, Neelamegham S, Haslam SM, Dimitroff CJ. Peracetylated 4-fluoro-glucosamine reduces the content and repertoire of N- and O-glycans without direct incorporation.
J. Biol. Chem., 2011; 286(24):21717-31.

Cedeno-Laurent F, Opperman MJ, Barthel SR, Hays D, Schatton T, Zhan Q, He X, Matta KL, Supko JG, Frank MH, Murphy GF, Dimitroff CJ. Metabolic inhibition of galectin-1-binding carbohydrates accentuates anti-tumor immunity.
J. Investigative Dermatology, 2012; 132(2):410-420.

Cedeno-Laurent F, Opperman MJ, Barthel SR, Kuchroo VK, Dimitroff CJ. Galectin-1 triggers an immunoregulatory signature defined by IL-10 expression.
J. Immunology, 2012; 188(7):3127-37.

Cedeno-Laurent F, Watanabe R, Teague JE, Kupper TS, Clark RA, Dimitroff CJ. Galectin-1 inhibits the viability, proliferation and Th1 cytokine production of non-malignant T cells in patients with leukemic cutaneous T cell lymphoma.
BLOOD, 2012; 119(15):3534-8.

Cedeno-Laurent F, Dimitroff CJ. Galectin-1 research in T cell immunity: Past, present and future.
Clinical Immunology, 2012; 142(2):107-16.

Cedeno-Laurent F, Dimitroff CJ. Evidence of a novel galectin-9-binding membrane glycoprotein ligands in T helper cells.
Clinical Immunology, 2012, 143(1):6-7.

Cedeno-Laurent F, Dimitroff CJ. Galectins and their ligands: Negative regulators of anti-tumor immunity.
Glycoconjugate J., 2012, 29(8-9):619-25.

Barthel SR, Hays DL, Yazawa EM, Opperman M, Walley KC, Nimrichter L, Burdick MM, Gillard BM, Moser MT, Pantel K, Foster BA, Pienta KJ and Dimitroff CJ. Definition of molecular determinants of prostate cancer cell bone extravasation.
Cancer Research, 2013; 73(2):942-952.

Dimitroff CJ. Leveraging fluorinated glucosamine action to boost anti-tumor immunity.
Current Opinion in Immunology, 2013, 25(2):206-13.

Dimitroff CJ. How to Build ‘Lean and Mean’ Anti-tumor T cells: A Strategic View into the Anti-Carbohydrate Action of Fluorinated Glucosamine Analogs.
Galectins and Disease Implications for Targeted Therapeutics (ACS Symposium Series, Vol. 1115), Oxford University Press, 2013: Chp. 7: 123-135.

Burdick MM, Reynolds NM, Martin EW, Hawes JV, Carlson GE, Cuckler CM, Bates MC, Barthel SR, Dimitroff CJ. Isolation and characterization of chimeric human Fc-expressing proteins using protein A membrane adsorbers and a streamlined workflow.
J. Visualized Experiments, In press.



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