Research Summary

My research interests are in the areas of protein function-structure relationship, protein-protein interactions, and the intervention of protein interactions by antibodies. Current research focuses are recombinant antibody library design, mAb discovery and engineering, immuno-diagnostics and therapeutics. I have worked on projects that include 1) the discovery and engineering of internalizing mAbs targeting basal subtype breast cancer associated membrane proteins for drug delivery, 2) the discovery and engineering of mAbs against serum biomarkers for pancreatic cancer early diagnosis, 3) engineering of antibody Fc to enhance antibody dependent cellular cytotoxicity (ADCC) and pharmacokinetics, 4) the development of host-targeted broad-spectrum anti-viral therapy, 5) the establishment of high-throughput antibody discovery platform, 6) development of therapeutic mAbs to immune-oncological targets, 7) design and construction of recombinant antibody libraries, and 8) impact of germline sequences to antibody developability. The high-throughput antibody discovery is powerful for generating data of antibody-antigen interactions, which can help uncover protein-protein interactions and the de novo design of antibodies. The phage display and yeast display platform allowed identifying mAbs with high affinity and cross-reactivity, can be applied to all immune-oncological targets.

Research Funding

  • July 1, 2024 - June 30, 2027 - Development of monoclonal antibody ultrasensitive assays for diagnosis of infant botulism , Co-Investigator . Sponsor: California Department of Public Health, Sponsor Award ID: 24-10011
  • March 1, 2024 - June 30, 2026 - A novel bispecific antibody to disrupt the B cell-T cell axis in multiple sclerosis and other autoimmune disease , PI . Sponsor: Weill Institute of Neurosciences, Sponsor Award ID:
  • July 1, 2021 - June 30, 2024 - Development of monoclonal antibody-based ultrasensitive assays for diagnosis of infant botulism , Co-Investigator . Sponsor: California Department of Public Health, Sponsor Award ID: A137212
  • July 1, 2021 - June 30, 2023 - Human mAbs to cell type specific antigens , Principal Investigator . Sponsor: Silvercreek Pharmaceuticals, Sponsor Award ID: A137160
  • November 1, 2014 - October 31, 2019 - The antibody technology research center: renewable antibodies to biomedical relevant antigens , Co-Investigator . Sponsor: NIH/NCI, Sponsor Award ID: 1P41CA196276-01
  • April 1, 2018 - March 31, 2019 - Internalizing and cross-reactive human mAbs to tumor associate antigen , Principal Investigator . Sponsor: ImmunoGen, Inc., Sponsor Award ID: A131104
  • August 1, 2016 - July 31, 2018 - Cross reactive human mAbs to tumor associated antigens , Principal Investigator . Sponsor: Merrimack Pharmaceuticals, Inc., Sponsor Award ID: A128580

Education

Peking University, Beijing, China, B.S., 1988, Biochemistry
Peking University, Beijing, China, M.S., 1991, Biochemistry
Peking University, Beijing, China, Ph.D., 2000, Molecular Biology
University of California, San Francisco, CA, Postdoc, 2001-2004, Cancer Therapeutics

Honors & Awards

  • 2006
    Best in Show Poster Award, Breast Cancer Oncology Scientific Retreat, UCSF
  • 2013
    Best Therapeutics & Clinical Trials Poster Award, Breast Cancer Oncology Scientific Retreat, UCSF

Selected Publications

  1. Fan Y, Sun Z, Conrad F, Wen W, Zhao L, Lou J, Zhou Y, Farr-Jones S, Marks JD. Multicolor fluorescence activated cell sorting to generate humanized monoclonal antibody binding seven subtypes of BoNT/F. PLoS One. 2022; 17(9):e0273512.  View on PubMed
  2. Muller YD, Ferreira LMR, Ronin E, Ho P, Nguyen V, Faleo G, Zhou Y, Lee K, Leung KK, Skartsis N, Kaul AM, Mulder A, Claas FHJ, Wells JA, Bluestone JA, Tang Q. Precision Engineering of an Anti-HLA-A2 Chimeric Antigen Receptor in Regulatory T Cells for Transplant Immune Tolerance. Front Immunol. 2021; 12:686439.  View on PubMed
  3. Tam EM, Fulton RB, Sampson JF, Muda M, Camblin A, Richards J, Koshkaryev A, Tang J, Kurella V, Jiao Y, Xu L, Zhang K, Kohli N, Luus L, Hutto E, Kumar S, Lulo J, Paragas V, Wong C, Suchy J, Grabow S, Dugast AS, Zhang H, Depis F, Feau S, Jakubowski A, Qiao W, Craig G, Razlog M, Qiu J, Zhou Y, Marks JD, Croft M, Drummond DC, Raue A. Antibody-mediated targeting of TNFR2 activates CD8+ T cells in mice and promotes antitumor immunity. Sci Transl Med. 2019 10 02; 11(512).  View on PubMed
  4. Kamoun WS, Kirpotin DB, Huang ZR, Tipparaju SK, Noble CO, Hayes ME, Luus L, Koshkaryev A, Kim J, Olivier K, Kornaga T, Oyama S, Askoxylakis V, Pien C, Kuesters G, Dumont N, Lugovskoy AA, Schihl SA, Wilton JH, Geddie ML, Suchy J, Grabow S, Kohli N, Reynolds CP, Blaydes R, Zhou Y, Sawyer AJ, Marks JD, Drummond DC. Antitumour activity and tolerability of an EphA2-targeted nanotherapeutic in multiple mouse models. Nat Biomed Eng. 2019 04; 3(4):264-280.  View on PubMed
  5. Zhou Y, Zou H, Yau C, Zhao L, Hall SC, Drummond DC, Farr-Jones S, Park JW, Benz CC, Marks JD. Discovery of internalizing antibodies to basal breast cancer cells. Protein Eng Des Sel. 2018 01 01; 31(1):17-28.  View on PubMed
  6. Le Gall M, Crépin R, Neiveyans M, Auclair C, Fan Y, Zhou Y, Marks JD, Pèlegrin A, Poul MA. Neutralization of KIT Oncogenic Signaling in Leukemia with Antibodies Targeting KIT Membrane Proximal Domain 5. Mol Cancer Ther. 2015 Nov; 14(11):2595-605.  View on PubMed
  7. Seldon TA, Pryor R, Palkova A, Jones ML, Verma ND, Findova M, Braet K, Sheng Y, Fan Y, Zhou EY, Marks JD, Munro T, Mahler SM, Barnard RT, Fromm PD, Silveira PA, Elgundi Z, Ju X, Clark GJ, Bradstock KF, Munster DJ, Hart DN. Immunosuppressive human anti-CD83 monoclonal antibody depletion of activated dendritic cells in transplantation. Leukemia. 2016 Mar; 30(3):692-700.  View on PubMed
  8. Li K, Zettlitz KA, Lipianskaya J, Zhou Y, Marks JD, Mallick P, Reiter RE, Wu AM. A fully human scFv phage display library for rapid antibody fragment reformatting. Protein Eng Des Sel. 2015 Oct; 28(10):307-16.  View on PubMed
  9. Zhao L, Qu L, Zhou J, Sun Z, Zou H, Chen YY, Marks JD, Zhou Y. High throughput identification of monoclonal antibodies to membrane bound and secreted proteins using yeast and phage display. PLoS One. 2014; 9(10):e111339.  View on PubMed
  10. Li K, Tavaré R, Zettlitz KA, Mumenthaler SM, Mallick P, Zhou Y, Marks JD, Wu AM. Anti-MET immunoPET for non-small cell lung cancer using novel fully human antibody fragments. Mol Cancer Ther. 2014 Nov; 13(11):2607-17.  View on PubMed
  11. Jones AR, Stutz CC, Zhou Y, Marks JD, Shusta EV. Identifying blood-brain-barrier selective single-chain antibody fragments. Biotechnol J. 2014 May; 9(5):664-74.  View on PubMed
  12. Carrico ZM, Farkas ME, Zhou Y, Hsiao SC, Marks JD, Chokhawala H, Clark DS, Francis MB. N-Terminal labeling of filamentous phage to create cancer marker imaging agents. ACS Nano. 2012 Aug 28; 6(8):6675-80.  View on PubMed
  13. Zhou Y, Zhao L, Marks JD. Selection and characterization of cell binding and internalizing phage antibodies. Arch Biochem Biophys. 2012 Oct 15; 526(2):107-13.  View on PubMed
  14. Zhou Y, Goenaga AL, Harms BD, Zou H, Lou J, Conrad F, Adams GP, Schoeberl B, Nielsen UB, Marks JD. Impact of intrinsic affinity on functional binding and biological activity of EGFR antibodies. Mol Cancer Ther. 2012 Jul; 11(7):1467-76.  View on PubMed
  15. Kirpotin DB, Noble CO, Hayes ME, Huang Z, Kornaga T, Zhou Y, Nielsen UB, Marks JD, Drummond DC. Building and characterizing antibody-targeted lipidic nanotherapeutics. Methods Enzymol. 2012; 502:139-66.  View on PubMed
  16. Zhou Y, Marks JD. Discovery of internalizing antibodies to tumor antigens from phage libraries. Methods Enzymol. 2012; 502:43-66.  View on PubMed
  17. Zhou Y, Zou H, Zhang S, Marks JD. Internalizing cancer antibodies from phage libraries selected on tumor cells and yeast-displayed tumor antigens. J Mol Biol. 2010 Nov 19; 404(1):88-99.  View on PubMed
  18. Diaz L, Mao H, Zhou Y, Kohli M, Cassella J, Santos D, Fesseha Z, Weng K, Chen H, Bamba D, Marks JD, Goldblatt M, Kinch M. TSG101 exposure on the surface of HIV-1 infected cells: implications for monoclonal antibody therapy for HIV/AIDS. Am J Transl Res. 2010 Jul 20; 2(4):368-80.  View on PubMed
  19. Lepin EJ, Leyton JV, Zhou Y, Olafsen T, Salazar FB, McCabe KE, Hahm S, Marks JD, Reiter RE, Wu AM. An affinity matured minibody for PET imaging of prostate stem cell antigen (PSCA)-expressing tumors. Eur J Nucl Med Mol Imaging. 2010 Aug; 37(8):1529-38.  View on PubMed
  20. Zhou Y, Marks JD. Identification of target and function specific antibodies for effective drug delivery. Methods Mol Biol. 2009; 525:145-60, xv.  View on PubMed

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