Charles J. Dimitroff
Our laboratory conducts research in the field of glyco-immunology, as it pertains to cancer development and metastasis and to inflammation and immune resolution. We are experts in the identification and structural and functional characterization of leukocyte glycans that impact their fate and function.
We have recently developed new galectin fusion proteins that can be used as mimetics of native galectins to bind galectin counter-receptor carbohydrate ligands on effector T cells, neutrophils and cancer cells. These binding activities have profound effects on cell viability and immune/tumor cell function. For example, we have received shown that galectin-1 – human Fc (Gal-1hFc) can kill effector T cells and/or create the development of type-1 regulatory T cells. Gal-1hFc is now being developed as a novel anti-inflammatory therapeutic in autoimmune models of psoriasis, arthritis and multiple sclerosis. In related studies, we show that fluorinated analogs of glucosamine can block the synthesis of Gal-1-binding carbohydrate ligands on effector anti-melanoma T cells, which can thusly spare Gal-1-mediated death. Because melanomas produce an abundance of Gal-1, these fluoro-glucosamine treatments block the elimination of melanoma-killing T cells and, thus, boost anti-tumor T cell immunity and elicit significant melanoma growth inhibition. We are now exploring this exciting pharmacologic approach in adoptive T cell treatment setting using innovative preclinical models of cancer.
Our contemporary laboratory has been continuously funded by the NIH and has been actively involved in the Harvard Immunology Program since 2005. My laboratory and its current members are committed to teaching/mentoring Ph.D. students on the mechanisms of immune/tumor cell trafficking and T cell immunity governed by the action carbohydrate-lectin interactions. We are also committed to mentoring young scientists through ongoing summer internship programs with local colleges and high schools. We teach hands-on laboratory methods in the fields of biochemistry, cutaneous immunology, glycobiology and tumor metastasis. Our training methods range from daily shoulder-to-shoulder instruction to didactic sessions in the form of journal clubs, weekly laboratory meetings and daily discussions on biomedical research.
In summary, we practice a multi-faceted approach to biomedical research, which fosters a state-of-the-art, evolving laboratory that spawns successful scientists at every academic level and lends to a solid National/International reputation and successful funding record.
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.
Last Update: 1/6/2014