Dr. Zhang’s research focuses on the Vaccine Development and the immune mechanism of protection against important human pathogens, including Streptococcus pneumoniae, Staphylococcus aureus, Mycobacterium tuberculosis, etc.
B- and T-cell mediated responses are two important arms of adaptive immunity, which provide different protection mechanisms against infectious diseases. Antibodies directed to the secreted toxins and the surface molecules, e.g. polysaccharides (PS) and membrane proteins, are highly effective against invasive infection of pathogens, whereas the immunity mediated by CD4+ T-cells, such as Th1 and Th17 cells, plays critical roles in the control and elimination of mucosal and intracellular pathogens.
Dr. Zhang has developed a novel technology, the multiple antigen presenting system (MAPS), which provides an efficient and effective platform to elicit comprehensive B- and T-cell immunity against PS and protein antigens. This technology has wide-range implications to the development of novel vaccines against many important human pathogens for which both humoral and cellular immunity play critical roles in protection. Candidate vaccines against a variety of pathogens, including S. pneumoniae, S. aureus, M. tuberculosis, and Salmonella typhi , have been designed and evaluated. Potent immune responses specific to the target pathogens have been observed in animals received candidate vaccines. Further preclinical studies on the protection of these vaccines against disease in animal models are ongoing. Roles of humoral and cellular immunity in the protection against different target pathogens are also investigated.
In addition to the vaccine development, I am also interested in using MAPS platform as a research tool to study how immune system responds differentially to various antigens and the underlying mechanisms. I wish to evaluate the effects of various chemical, physical and molecular properties of antigens in the activation of antibody and cellular immune responses, and to identify co-factors that can facilitate or inhibit specific type of humoral or cellular immunity.
About Dr. Zhang
Fan Zhang received her PhD from Tsinghua University in China. She undertook Postdoctoral training first in the Department of Molecular Biology at Princeton University, and then in the Division of Infectious Disease at Boston Children’s Hospital.
1. Lu YJ, Zhang F, Sui SF. Specific binding of integrin alphaIIbbeta3 to RGD peptide immobilized on a nitrilotriacetic acid chip: a surface plasmon resonance study. Biochemistry (Mosc), 2002, 67 (8): 933-939.
2. Zhang F, Lu YJ, Wang SX, Sui SF. The effects of protein hydrophobic exposure on the slope of the line in the deltapi vs pi(i) plot. IUBMB Life, 2002, 54 (2): 73-79.
3. Zhang F, Lu YJ, Shaw PC, Sui SF. Change in pH-dependent membrane insertion characteristics of trichosanthin caused by deletion of its last seven C-terminal amino acid residues. Biochemistry (Mosc), 2003, 68 (4): 436-445.
4. Xia XF, Zhang F, Shaw PC, Sui SF. Trichosanthin induces leakage and membrane fusion of liposome. IUBMB Life, 2003, 55 (12): 681-687.
5. Li RF, Zhang F, Lu YJ, Sui SF. Specific interaction between Smad1 and CHIP: a surface plasmon resonance study. Colloids Surf B Biointerfaces, 2005, 40 (3-4): 133-136.
6. Zhang F and Sui SF. Insertion of Trichosanthin into lipid membrane with similar composition to the non-cytosolic leaflet of plasma membrane. ACTA BIOPHYSICA SINICA, 2005, 21: 169-175
7. Zhang F and Sui SF. Internalization of Trichosanthin via different endocytic mechanisms. Tsinghua Science and Technology, 2005, 10: 430-434.
8. Lu YJ*, Zhang F*, Grimes KD, Lee RE and Rock CO. Topology and active site of PlsY: the bacterial acylphosphate: glycerol-3-phosphate acyltransferase. (*Co-first author) J Biol Chem, 2007, 282: 11339-46.
9. Zhang F*, Sun S*, Feng D*, Zhao WL and Sui SF. A Novel Strategy for the Invasive Toxin: Hijacking Exosome-Mediated Intercellular Trafficking. (*Co-first author) Traffic, 2009, 10: 411-424.
10. Zhang F, Hu M, Tian G, Zhang P, Finley D, Jeffrey P, Shi Y. Structural Insights Into The Regulatory Particle Of The Proteasome From Methanocaldococcus jannaschii. Mol Cell, 2009, 34(4): 473-484 (Cover Story).
11. Zhang F, Wu Z, Zhang P, Tian G, Finley D, Shi Y. Mechanism of Substrate Unfolding and Translocation Proteasome from Methanocaldococcus jannaschii. Mol Cell, 2009, 34(4): 485-496
12. Roelofs J, Park S, Haas W, Tian G, Lee BH, Zhang F, Shi Y, Gygi SP, Finley D. Chaperone-mediated pathway of proteasome regulatory particle assembly. Nature, 2009, 459(7248): 787-788.
13. Zhao WL, Zhang F, Feng D, Wu J, Chen S, Sui SF. A novel sorting strategy of trichosanthin for hijacking human immunodeficiency virus type 1. Biochem Biophys Res Commun. 2009, 384(3):347-51.
14. Lu YJ, Zhang F, Sayeed S, Thompson C, Szu S, Schneerson R, Robbins J, Anderson PW and Malley R. A Bivalent Vaccine to Protect against Streptococcus pneumoniae and Salmonella typhi. Vaccine, 2012, 30(23): 3405-12.
15. Basset A, Zhang F, Benes C, Sayeed S, Herd M, Thompson C, Golenbock DT, Camilli A, Malley R. Toll-like receptor (TLR) 2 mediates inflammatory responses to oligomerized RrgA pneumococcal pilus type 1 protein. J Biol Chem, 2013, 288(4): 2665-75.
16. Zhang F, Lu YJ & Malley R. Multiple antigen-presenting system (MAPS) to induce comprehensive B- and T-cell immunity. Proc Natl Acad Sci U S A, 2013, 110(33), 13564-9.
17. Sorge N, Cole J, Kuipers K, Henningham A, Ramy K, Kasirer-Friede A, Lin L, Berends E, Davies M, Dougan G, Zhang F, Dahesh S, Shaw L, Gin J, Cunningham M, Merriman J, Hütter J, Lepenies B, Rooijakkers S, Malley R, Walker M, Shattil S, Schlievert P, Choudhury B, Nizet V. The Classical Lancefield Antigen of Group A Streptococcus is a Virulence Determinant with Implications for Vaccine Design. Cell Host Microbe, 2014, 15 (6): 729-40.
18. Choi EH*, Zhang F*, Lu YJ, Malley R (2015) Capsular Polysaccharide (CPS) Release by Serotype 3 Pneumococcal Strains Reduces the Protective Effect of Anti-Type 3 CPS Antibodies. Clin Vaccine Immunol 23: 162-167.