Photo of Wayne A. Marasco,  MD, PhD

Wayne A. Marasco, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-2153
Fax: (617) 632-3889


wayne_marasco@dfci.harvard.edu

Wayne A. Marasco, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Medicine, Harvard Medical School
  • Professor, Cancer Immunology and Virology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

My research interests are in the field of human antibody engineering and the use of human antibodies in discovery research and in the treatment of human diseases. I am a physician/scientist with clinical training in Infectious Diseases. My clinical subspecialty training is in the care of immunocompromised patients with bone marrow and solid organ transplants and cancer. My clinical practice has had a profound influence on the research conducted in my laboratory at Dana-Farber Cancer Institute. During my rotations on the inpatient Infectious Disease service at BWH/DFCI, I supervise ID fellows and medical residents in the management of infections in immunocompromised patients. As a principal investigator, I supervise two junior faculty, seven post-doctoral fellows/scholars and five research technicians. This supervision involves mentorship roles in bench and clinical research, manuscript review and grant writing. On the national level, I am a member of the AIDS Immunopathogenesis study section and have a leadership role in the organization of and presentation at targeted gene therapy and antibody engineering meetings.

My laboratory is working in the areas of HIV/AIDS, emerging infectious diseases (SARS, highly pathogenic H5N1 avian influenza (bird flu), West Nile Virus (encephalitis), Denge virus (hemorrhagic fever)) and cancer (Adult T-cell Leukemia (HTLV-1), breast CA, renal cell carcinoma (RCC), cutaneous T-cell Lymphoma (CTCL)). This breadth of research is made possible because of two research developments in my laboratory in the field of human antibody engineering. The first is our seminal discovery that human antibodies can not only be used to target proteins on the surface of cells and microbes but can also be used in the form known as intracellular antibodies or intrabodies, which can be delivered to cells by gene transfer techniques. In this way, human antibodies can be expressed in different subcellular compartments inside cells where they can bind to their target protein and modulate its function. The second research development in my laboratory is the construction and characterization of one of the largest human antibody phage display libraries ever made (27 billion members). We have validated the quantity and high quality of the human antibodies that can be obtained from this library through the discoveries that we have made in the research areas mentioned above. Ongoing pre-clinical studies and clinical trials using human monoclonal antibodies (Mabs) are moving forward for the prevention and treatment of SARS and flavivirus diseases including West Nile virus encephalitis. We are also moving forward with a genetic/cellular therapy for the treatment of RCC.

In an effort to greatly expand the use of human monoclonal antibodies (Mab) in the treatment of cancer, I founded the National Foundation of Cancer Research (NFCR) Center for Therapeutic Antibody Engineering (CTAE) (http://www.nfcr-ctae.org/). My CTAE laboratory at Dana-Farber Cancer Institute is working with cancer investigators around the globe to utilize our human antibody library to discover new human Mab for the treatment of cancer. In this way, the CTAE can facilitate a broad range of discovery and translational research in cancer that would not be possible for a single laboratory. This also allows CTAE to work with some of the most accomplished cancer investigators in the world.

www.marascolab.com

Publications from Harvard Catalyst Profiles

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  • Wang Y, Buck A, Grimaud M, Culhane AC, Kodangattil S, Razimbaud C, Bonal DM, Nguyen QD, Zhu Z, Wei K, O'Donnell ML, Huang Y, Signoretti S, Choueiri TK, Freeman GJ, Zhu Q, Marasco WA. Anti-CAIX BBζ CAR4/8 T cells exhibit superior efficacy in a ccRCC mouse model. Mol Ther Oncolytics 2022; 24:385-399. PubMed
  • Wang Y, Chan LL, Grimaud M, Fayed A, Zhu Q, Marasco WA. High-Throughput Image Cytometry Detection Method for CAR-T Transduction, Cell Proliferation, and Cytotoxicity Assays. Cytometry A 2020. PubMed
  • Saleh FM, Chandra PK, Lin D, Robinson JE, Izadpanah R, Mondal D, Bollensdorff C, Alt EU, Zhu Q, Marasco WA, Braun SE, Abdel-Motal UM. A New Humanized Mouse Model Mimics Humans in Lacking α-Gal Epitopes and Secreting Anti-Gal Antibodies. J Immunol 2020; 204:1998-2005. PubMed
  • Magnotti EL, Chan LL, Zhu Q, Marasco WA. A high-throughput chemotaxis detection method for CCR4 T cell migration inhibition using image cytometry. J Immunol Methods 2020; 479:112747. PubMed
  • Magnotti E, Marasco WA. The latest animal models of ovarian cancer for novel drug discovery. Expert Opin Drug Discov 2018; 13:249-257. PubMed
  • Watson CT, Glanville J, Marasco WA. The Individual and Population Genetics of Antibody Immunity. Trends Immunol 2017; 38:459-470. PubMed
  • Suarez ER, Chang DK, Sun J, Sui J, Freeman GJ, Signoretti S, Zhu Q, Marasco WA. Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model. 2016. PubMed
  • Chang DK, Kurella VB, Biswas S, Avnir Y, Sui J, Wang X, Sun J, Wang Y, Panditrao M, Peterson E, Tallarico A, Fernandes S, Goodall M, Zhu Q, Brown JR, Jefferis R, Marasco WA. Humanized mouse G6 anti-idiotypic monoclonal antibody has therapeutic potential against IGHV1-69 germline gene-based B-CLL. MAbs 2016. PubMed
  • Chang DK, Peterson E, Sun J, Goudie C, Drapkin RI, Liu JF, Matulonis U, Zhu Q, Marasco WA. Anti-CCR4 monoclonal antibody enhances antitumor immunity by modulating tumor-infiltrating Tregs in an ovarian cancer xenograft humanized mouse model. Oncoimmunology 2016; 5:e1090075. PubMed
  • Chang DK, Moniz RJ, Xu Z, Sun J, Signoretti S, Zhu Q, Marasco WA. Human anti-CAIX antibodies mediate immune cell inhibition of renal cell carcinoma in vitro and in a humanized mouse model in vivo. Mol Cancer 2015; 14:119. PubMed
  • Tang XC, Agnihothram SS, Jiao Y, Stanhope J, Graham RL, Peterson EC, Avnir Y, Tallarico AS, Sheehan J, Zhu Q, Baric RS, 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. PubMed
  • Avnir Y, 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, Marasco WA. Molecular signatures of hemagglutinin stem-directed heterosubtypic human neutralizing antibodies against influenza A viruses. PLoS Pathog. 2014; 10:e1004103. PubMed
  • Hall SR, 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 Transl Med 2013; 2:567-78. PubMed
  • Zhang J, Valianou M, Simmons H, Robinson MK, Lee HO, Mullins SR, Marasco WA, Adams GP, Weiner LM, Cheng JD. Identification of inhibitory scFv antibodies targeting fibroblast activation protein utilizing phage display functional screens. FASEB J. 2013. PubMed
  • 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; 11:2451-61. PubMed
  • 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:e44455. PubMed
  • Vyas JM, Marasco WA. Fatal fulminant hepatic failure from adenovirus in allogeneic bone marrow transplant patients. Case Rep Infect Dis 2012; 2012:463569. PubMed
  • Kuan CT, Srivastava N, McLendon RE, Marasco WA, Zalutsky MR, Bigner DD. Recombinant single-chain variable fragment antibodies against extracellular epitopes of human multidrug resistance protein MRP3 for targeting malignant gliomas. Int J Cancer 2010; 127:598-611. PubMed
  • Xu C, Lo A, Yammanuru A, Tallarico AS, Brady K, Murakami A, Barteneva N, Zhu Q, Marasco WA. Unique biological properties of catalytic domain directed human anti-CAIX antibodies discovered through phage-display technology. PLoS ONE 2010; 5:e9625. PubMed
  • Nakase K,Cheng J,Zhu Q,Marasco WA. Mechanisms of SHP-1 P2 promoter regulation in hematopoietic cells and its silencing in HTLV-1-transformed T cells. J Leukoc Biol 2009; 85:165-74. PubMed
  • Lo AS, Zhu Q, Marasco WA. Intracellular antibodies (intrabodies) and their therapeutic potential. Handb Exp Pharmacol 2008. PubMed
  • Taube R,Zhu Q,Xu C,Diaz-Griffero F,Sui J,Kamau E,Dwyer M,Aird D,Marasco WA. Lentivirus display: stable expression of human antibodies on the surface of human cells and virus particles. PLoS ONE 2008; 3:e3181. PubMed
  • Marasco WA, Sui J. The growth and potential of human antiviral monoclonal antibody therapeutics. Nat Biotechnol 2007; 25:1421-34. PubMed
  • Li W, Sui J, Huang IC, Kuhn JH, Radoshitzky SR, Marasco WA, Choe H, Farzan M. The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2. Virology 2007; 367:367-74. PubMed
  • Cheng J, Kydd AR, Nakase K, Noonan KM, Murakami A, Tao H, Dwyer M, Xu C, Zhu Q, Marasco WA. Negative regulation of the SH2-homology-containing protein-tyrosine phosphatase-1 (SHP-1) P2 promoter by the HTLV-1 tax oncoprotein. Blood 2007; 110:2110-20. PubMed
  • Xu C, Sui J, Tao H, Zhu Q, Marasco WA. Human anti-CXCR4 antibodies undergo VH replacement, exhibit functional V-region sulfation, and define CXCR4 antigenic heterogeneity. J Immunol 2007; 179:2408-18. PubMed
  • Hwang WC, Lin Y, Santelli E, Sui J, Jaroszewski L, Stec B, Farzan M, Marasco WA, Liddington RC. Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R. J Biol Chem 2006; 281:34610-6. PubMed
  • Kanai R, Kar K, Anthony K, Gould LH, Ledizet M, Fikrig E, Marasco WA, Koski RA, Modis Y. Crystal structure of west nile virus envelope glycoprotein reveals viral surface epitopes. J Virol 2006; 80:11000-8. PubMed
  • Bai J, Demirjian A, Sui J, Marasco W, Callery MP. Histone deacetylase inhibitor trichostatin A and proteasome inhibitor PS-341 synergistically induce apoptosis in pancreatic cancer cells. Biochem Biophys Res Commun 2006; 348:1245-53. PubMed
  • Yuan QA, Simmons HH, Robinson MK, Russeva M, Marasco WA, Adams GP. Development of engineered antibodies specific for the Müllerian inhibiting substance type II receptor: a promising candidate for targeted therapy of ovarian cancer. Mol Cancer Ther 2006; 5:2096-105. PubMed
  • Tarnovitski N, Matthews LJ, Sui J, Gershoni JM, Marasco WA. Mapping a Neutralizing Epitope on the SARS Coronavirus Spike Protein: Computational Prediction Based on Affinity-selected Peptides. J Mol Biol 2006; 359:190-201. PubMed
  • Si Z, Vandegraaff N, O'huigin C, Song B, Yuan W, Xu C, Perron M, Li X, Marasco WA, Engelman A, Dean M, Sodroski J. Evolution of a cytoplasmic tripartite motif (TRIM) protein in cows that restricts retroviral infection. Proc Natl Acad Sci U S A 2006; 103:7454-9. PubMed
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