BBS Faculty Member - Wayne Marasco

Wayne Marasco

Department of Medicine

Dana Farber Cancer Institute
450 Brookline Ave., JF 824
Boston, MA 02215
Tel: 617-632-2153
Fax: 617-632-3113
Email: wayne_marasco@dfci.harvard.edu
Visit my lab page here.



Our laboratory research focuses on the engineering of human antibodies and the use of human antibodies in discovery research and disease treatment. We are working in three disease areas: emerging infectious diseases, cancer and HIV/AIDS. We have constructed and characterized several of the largest human antibody phage display libraries ever made with tens of billions of members. Numerous human antibody engineering discoveries in our laboratory have allowed us to validate the quantity and high quality of the human antibodies in this library. Our laboratory uses all of the modern molecular techniques to isolate and characterize human monoclonal antibodies (mAbs) including phage, yeast and mammalian display, human CD34+ stem cell reconstructed mice, memory B-cell immortalization by EBV and TLR4 ligands, in silico modeling and co-crystallographic studies. We have all of the expertise necessary to move human mAbs into clinical trials.

Our laboratory is pursuing active research programs in human monoclonal antibody immunotherapy. In the field of infectious diseases, we are discovering and targeting highly conserved epitopes on viral glycoproteins that are recalcitrant to neutralization escape. These include influenza A and B hemagglutinin and neuraminidase, Spike protein of human SARS and MERS coronaviruses and E-protein on flaviviruses including West Nile Virus and Denge serotypes 1-4. In the field of cancer immunotherapy, we are targeting CXCR4 and CAIX on different solid tumors such as breast cancer and renal cell carcinoma. We are also developing mAbs targeting molecules that are involved in checkpoint control of human T cells such as PD1-L and reversal of regulatory T cell (Treg) suppression including CCR4 to augment and boost natural and vaccine induced immunity for infectious and cancer vaccines. We have also spent considerable time developing adult stem cell reconstructed humanized mouse models and several models are available to use in mechanistic and therapeutic studies (http://www.humouse.org) and stem cell medicine studies (http://hsci.harvard.edu/humanized-neonatal-mouse-center-hnmc). In addition, we also founded the National Foundation for Cancer Research Center for Therapeutic Engineering (NFCR-CTAE) to assist cancer investigators with the isolation and characterization of new anticancer human monoclonal antibodies (see http://research4.dfci.harvard.edu/nfcr-ctae/) and CHAT to discover human antibody drugs that can lead to differentiation of stem cells down directed lineage pathways (see http://hsci.harvard.edu/center-human-antibody-therapeutics-chat).



Last Update: 7/8/2014



Publications

For a complete listing of publications click here.

 


 

Sui J, Hwang WC, 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; 16(3):265-73. PMID: 19234466 PMCID: PMC2692245.

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.

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; PMID: 21460314.

Avnir A, Tallarico AS. Zhu Q, Bennett AS, Connelly G, Sheehan J, Sui J, Fahmy A, Huang CY, Cadwell G, Bankston LA, McGuire AT, Stamatatos L, Wagner G, Liddington RC, and
Marasco WA. Molecular Signatures of Hemagglutinin Stem-Directed Heterosubtypic Human Neutralizing Antibodies Against Influenza A Viruses. PLoS Pathogens. 2014 May 1;10(5):e1004103. PMID: 24788925.

Tang XC, Agnihothram SS, Jiao Y, Stanhope J, Graham RL, Peterson E, Avnir Y, Sheehan J, Zhu Q, Baric RS, and
Marasco WA. Identification of Human Neutralizing Antibodies against MERS-CoV and Their Role in Virus Adaptive Evolution. Proc Natl Acad Sci U S A. 2014 May 13;111(19):E2018-26. PMID: 24778221.

Abdel-Motal U, Harbison C, Han T, Pudney J, Anderson D, Zhu Q, Westmoreland S, and
Marasco W. Prolonged Expression of an Anti-HIV-1 gp120 Minibody to the Female Rhesus Macaque Lower Genital Tract by AAV Gene Transfer. Gene Ther. 2014 Jun 26. doi: 10.1038/gt.2014.56. PMID: 24965083.



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