Research Department

Cancer Immunology and AIDS

Area of Research

Human Monoclonal Antibody-Based Immunotherapy

Biography

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.

Research

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 VH1-69 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. 

We also 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, 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 secretd products can revers 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). 

Select Publications

• 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.
• Hashem AM, Van Domselaar G, Li C, Wang J, She YM, Cyr TD, Sui J, He R, Marasco WA, Li X. Universal Antibodies against the Highly Conserved Influenza Fusion Peptide Cross-Neutralize Several Subtypes of Influenza A Virus. Biochem Biophys Res Commun. 2010 Dec 10; 403(2):247-51. PMID: 21078301.
• Herschhom A, Marasco WA, Hizi A. Antiobodies and Lentiviruses that Specifically Recognize a T-cell Epitope Derived from HIV-1 Nef Protein and Presented by HLA-C. J Immunol. 2010 Dec 15; 185(12):7623-32. PMID: 21076072.
• Xu C, Lo A, Yammanuru A, Tallarico AS, Brady K, Murakami A, Barteneva N, Zhu QK, and Marasco WA. Unique biological properties of catalytic domain directed human anti-CAIX antibodies discovered through phage-display technology. PLoS ONE. 2010 March 10;5(3):e9625. PMID: 20224781.
• 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.
• Wrammert J, Koutsonanos D, Li GM, Edupuganti S, Sui J, Morrissey M, McCausland M, Skountzou I, Hornig M, Lipkin WI, Mehta A, Razavi B, Del Rio C, Zheng NY, Lee JH, Huang M, Ali Z, Kaur K, Andrews S, Amara R, Wang Y, Das S, Yewdell J, Subbarao K, Marasco WA, Mulligan MJ, Compans R, Ahmed R, Wilson PC. Broadly cross-reactive antibodies dominate the acute B cell response against novel 2009 H1N1 invluenza virus infection. J Exp Med. 2011 Jan 17;208(1):181-93. PMCID: PMC3023136.

Investigators

• Sun, Jiusong, PhD
• Tallarico, Aimee, PhD
• Zhu, Quan, PhD
• Sui, Jianhua, MD, PhD

Trainees

• Abdel-Motal, Ussama, PhD
• Avnir, Yuval, PhD
• Biswas, Subhabrata (Brad), PhD
• Chang, DeKuan, PhD
• Fu, Ying, MD, PhD
• Han, Thomas, PhD
• Kurella, Vinodh, PhD
• Moniz, Raymond, PhD
• Tang, Xianchun, PhD
• Zhang, Zhen, PhD