Wayne A. Marasco, MD, PhD
Professor of Medicine, Harvard Medical School
Office phone: 617-632-2153
Website: Marasco Laboratory
Preferred contact method: email
Area of Research
Human Monoclonal Antibody-Based Immunotherapy
Dana-Farber Cancer Institute
450 Brookline Avenue
Jimmy Fund 824
Boston, MA 02215
Dr. Marasco received his PhD in 1980 from the University of Connecticut School of Medicine and postdoctoral training at the University of Michigan Medical School, where he also earned an MD in 1986 and completed training in internal medicine. He received his subspecialty training in infectious diseases at Harvard Medical School, and joined DFCI in 1989. In 2003, he founded the National Foundation of Cancer Research Center for Therapeutic Antibody Engineering to expand the use of human monoclonal antibodies in the treatment of cancer. In 2009, he was listed among 13 top scientists in their field as the 21st century medicine "Pioneeers of Medicine Progress" by US News & World report. He is head of an accomplished research laboratory in the area of cancer and infectious disease immunotherapy.
- "Pioneer of Medical Progress", U.S. News & World Report (among 13 top scientists in their field), 2009
ResearchHuman Monoclonal Antibody-Based Immunotherapy
Our laboratory focuses on the engineering and use of human antibodies in discovery research and disease treatment. We are working in three disease areas: cancer, emerging infectious diseases, and HIV/AIDS, a breadth of investigation made possible by the development and use of state-of-the-art tools in the field of antibody engineering that support our research efforts. More recently, we have been developing humanized mice to support our targeted immunotherapy studies and to investigate the roles of human adult stem cells in regenerative medicine.
We have active research programs in cancer immunotherapy that include the following targets: CXCR4 for breast cancer, G250 (CA IX) for renal cell carcinoma, CCR4 for cutaneous T cell lymphomas (CTCLs), and IGHV1-69 encoded B-cell receptors (BCR) for treatment of an aggressive form of chronic lymphocytic leukemia (CLL).
We are also developing immunotherapies that can modulate immune T cell activity to boost natural cancer immunity and response to cancer vaccines. Regulatory T cells (Tregs) exert control by dampening the immune response to prevent host tissue damage but these cells are also co-opted by cancer cells which leads to immune evasion. Tregs express high levels of CCR4 and we have demonstrated in vitro and in vivo that anti-CCR4 Mabs can reverse this immune suppression and reverse T cell "exhaustion" thereby restoring host immunity.
We use human monoclonal antibodies in functional and structural studies to understand mechanisms of viral entry, identify common targets that povide broad-spectrum protection, and develop strategies that prevent the viruses from undergoing neutralization escape. Vaccinated/infected humans and humanized mice are the B-cell sources of antibody genes for these studies. We are studying human pathogenic viruses that include influenza A, West Nile Virus, SARS- and MERS-CoVs and HIV/AIDS. As with our cancer studies, we are investigating whether human antibodies that are directed to surface proteins on T-cells or their secreted products can reverse T-cell "exhaustion" which is known to occur in HIV-1/AIDS with the goal of lowering viral loads, prolonging health and preventing the spread of HIV-1. We are using our humanized mice in the area of anti-microbial immunity to develop broad-spectrum anti-viral vaccines.
The laboratory has made major scientific advances in the treatment of infectious diseases and cancer (see www.marascolab.org).
- Sui J, Hwang WV, Perez S, Wei G, Aird D, Chen L, Santelli E, Stec B, Cadwell G, Ali M, Wan H, Murakami A, Yammanuru A, Han T, Cox N, Bankston LA, Donis RO, Liddington RC and Marasco WA. Structural and Functional Bases for Broad-Spectrum Neutralization of Avian and Human Influenza A Viruses. Nat Struct Mol Biol. 2009 Feb 22. PMCID: PMC2692245.
- Abdel-Motal U, Sarkis PTN, Han T, Pudney J, Anderson DJ, Zhu Q, Marasco WA. Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro. PLoS One. 2011, 2011;6(10):e26473. PMCID: PMC3198777.
- Biswas S, Chang H, Sarkis PTN, Fikrig E, Zhu Q and Marasco WA. Humoral immune responses in humanized BLT mice immunized with West Nile virus and HIV-1 envelope proteins are largely mediated via human CF5+ B cells. Immunology, 2011, Dec;134(4):419-33. PMID:22044090.
- Han T, Sui J, Bennett AS, Liddington RC, Donis RO, Zhu Q and Marasco WA. Fine epitope mapping of monoclonal antibodies against hemagglutinin of a highly pathogenic H5N1 influenza virus using yeast surface display. Biochem Biophys Res Commun. 2011; Epub ahead of print. PMCID: PMC3119598.
- Sui J, Sheehan J, Hwang WC, Bankston LA, Burchett SK, Huang CY, Liddington R, Beigel JH, and Marasco WA. Wide Prevalence of Heterosubtypic Broadly Neutralizing Human Anti-Influenza A Antibodies. Clinical Infectious Diseases. 2011 Apr 15;52(8):1003-9; PMID:21460314.
- Han T and Marasco, WA. Structural basis of influenza virus neutralization. Ann N Y Acad Sci. The Year in Immunology. 2011 Jan;1217(1):178-90. PMID:21251008.
- Chang H, Biswas S, Tallarico AST, Sarkis P, Geng S, Panditrao MM, Zhu Q, Marasco WA. Human B-cell ontogeny in humanized NOD/SCID γc(null) mice generates a diverse yet auto/poly- and HIV-1 reactive antibody repertoire. Genes Immun. 2012 Jul;13(5):399-410. PMID: 22592523; PMCID: PMC3411862.
- Chang DK, Sui J, Geng S, Muvaffak A, Bai M, Fuhlbrigge RC, Lo A, Yammanuru A, Hubbard L, Sheehan J, Campbell JJ, Zhu Q, Kupper TS, Marasco WA. Humanization of an anti-CCR4 antibody that kills Cutaneous T Cell Lymphoma cells and abrogates suppression by T regulatory cells. Mol. Cancer Ther. 2012 Nov;11(11):2451-61. PMID: 22869555; PMCID: PMC3496034.
- Han T, Abdel-Motal UM, Chang DK, Sui J, Muvaffak A, Campbell J, Zhu Q, Kupper TS, Marasco WA. Human Anti-CCR4 Minibody Gene Transfer for the Treatment of Cutaneous T-Cell Lymphoma. PLoS One. 2012;7(9):e44455. Epub 2012 Sept 4. PMID: 22973452; PMCID: PMC3433438.
- Hall SRR, Jiang Y, Leary E, Yavanian G, Eminli S, O’Neill DW, Marasco WA. Identification and Isolation of small CD44 negative mesenchymal stem/progenitor cells from human bone marrow using elutriation and polychromatic flow cytometry. Stem Cells Translational Medicine. 2013 Aug;2(8):567-78. PMID:23847000. PMCID: PMC3726136.
- Zhu, Quan, PhD
- Tallarico, Aimee, PhD
- Sun, Jiusong, PhD
- Edward, Cohen, PhD
- Avnir, Yuval, PhD
- Biswas, Subhabrata (Brad), PhD
- Chang, DeKuan, PhD
- Fu, Ying, MD, PhD
- Tang, Xianchun, PhD
- Zhang, Zhen, PhD