Min Zhang, PhD
Assistant Research Professor
For the past 10 years most of my efforts have been dedicated to studying the translational control in Plasmodium parasites and structure-based malaria vaccine development. The focus of my research is on translational control in the latent parasites related to drug resistance.
2007-2013 Postdoctoral Fellow
New York University School of Medicine
Advisor: Victor Nussenzweig
Fudan University School of Life Sciences, China
Advisor: Honghai Wang
Hubei University, China
For the past 10 years most of my efforts have been dedicated to studying the translational control in malaria parasites in Dr. Victor Nussenzweig’s lab at New York University. I have also enjoyed a long standing partnership with Dr. William J. Sullivan Jr. at Indiana University to study translational control in malaria parasites.
Plasmodium sporozoites in mosquitoes, and gametocytes in patient blood, are adapted for long-term survival while maintaining their infectivity. I have identified two proteins that control the latency of malaria sporozoites that reside in the salivary glands of mosquitoes: Plasmodium eukaryotic initiation factor 2α (eIF2α) kinase eIK2, and phosphatase UIS2 (J. Exp. Med. 207, 1465-1474; PLoS Pathog. 12, e1005370). I also found another eIF2α kinase, PK4, which leads to the arrest of global protein synthesis in blood-stage schizonts and gametocytes (Proc. Natl. Acad. Sci. USA 109, 3956-3961). In summary, I have uncovered the mechanism of malaria latency in the normal malaria life cycle, and summarized my research accomplishments in a review paper (Eukaryot. Cell 12:161-167).
I am co-mentored by Dr. William Sullivan, Dr. Ronald Wek, and Dr. Chandy John to continue my study of translational control in Plasmodium and Toxoplasma.
Artemisinin and its derivatives are the most potent anti-malaria drugs. Nevertheless, artemisinin therapy is associated with accumulation of latent parasites and with recrudescence of Plasmodium infection, which is a clinical treatment failure. Artemisinin resistance is a major threat to global public health. The focus of my interest is the translational control in the drug resistant and artemisinin-induced latent parasites.
RTS,S/AS01 , trade name Mosquirix , is a most clinically advanced malaria vaccine approved for use by European regulators in July 2015. Phase III trial data demonstrated that the standard three-dose vaccination (RTS,S-SD) reduced clinical malaria cases by <50%. In collaboration with Dr. Xiangpeng Kong at New York University, we are working on structure-based immunogen design in malaria vaccine discovery.
1. Zhang M*, Mishra S, Sakthivel R, Fontoura BM, Nussenzweig V. UIS2: A Unique Phosphatase Required for the Development of Plasmodium Liver Stages. PLoS Pathog. 2016 Jan 6;12(1):e1005370. (*corresponding author)
2. Zhang M, Kaneko I, Tsao T, Mitchell R, Nardin EH, Iwanaga S, Yuda M, Tsuji M. A highly infectious Plasmodium yoelii parasites, bearing Plasmodium falciparum circumsporozoite protein. Malar J. 2016; 15:201.
3. Huang J, Tsao T, Zhang M, Rai U, Tsuji M, Li X. A sufficient role of MHC class I molecules on hepatocytes in anti-plasmodial activity of CD8 (+) T cells in vivo. Front Microbiol. 2015; 6:69.
4. da Silva Augusto L, Moretti NS, Ramos TC, de Jesus TC, Zhang M, Castilho BA, Schenkman S.A membrane-bound eIF2 alpha kinase located in endosomes is regulated by heme and controls differentiation and ROS levels in Trypanosoma cruzi.PLoS Pathog. 2015 Feb 6;11(2):e1004618.
5. Huang J, Li X, Coelho-Dos-Reis JG, Zhang M, Mitchell R, et al. Human immune system mice immunized with Plasmodium falciparum circumsporozoite protein induce protective human humoral immunity against malaria. J Immunol Methods. 2015. pii: S0022-1759(15)30047-8.
6. Xiangming Li, Akira Kawamura, Chasity D. Andrews, Jessica Miller, Douglass Wu, Min Zhang, Tiffany Tsao, Ryota Funakoshi, Jing Huang, Deena A Oren, Neal N. Padte, Steven A Porcelli, Chi-Huey Wong, Stefan H.I. Kappe, David D Ho, Moriya Tsuji. Colocalization of a CD1d-Binding Glycolipid with a Radiation-Attenuated Sporozoite Vaccine in Lymph Node-Resident Dendritic Cells for a Robust Adjuvant Effect. J Immunol. 2015;195(6):2710-21.
7. Huang J, Tsao T, Zhang M, Tsuji M. Circumsporozoite Protein-Specific K(d)-Restricted CD8+ T Cells Mediate Protective Antimalaria Immunity in Sporozoite-Immunized MHC-I-K(d) Transgenic Mice. Mediators Inflamm. 2014:728939.
8. Zhang M, Mishra S, Sakthivel R, Rojas M, Ranjan R, et al. PK4, an eIF2alpha kinase, is essential for the development of the erythrocytic cycle of Plasmodium. Proc Natl Acad Sci USA. 2012; 109:3956-3961.
9. Zhang M, Fennell C, Ranford-Cartwright L, Sakthivel R, Gueirard P, et al. The Plasmodium eukaryotic initiation factor-2α kinase IK2 controls the latency of sporozoites in the mosquito salivary glands. J Exp Med. 2010; 207: 1465-1474.
10. Wang Q, Yue J, Zhang L, Xu Y, Chen J, Zhang M, Zhu B, Wang H, Wang H. A Newly Identified 191A/C Mutation in the Rv2629 Gene that Was Significantly Associated with Rifampin Resistance in Mycobacterium tuberculosis. J Proteome Res. 2007; 6(12):4564-71.
11. Shi W, Feng J, Zhang M, Lai X, Xu S, Zhang X, Wang H. Biosynthesis of isoprenoids: characterization of a functionally active recombinant 2-C-methyl-D-erythritol 4-phosphate cytidyltransferase (IspD) from Mycobacterium tuberculosis H37Rv. J Biochem Mol Biol. 2007; 40(6):911-20.
12. Wang J, Li Y, Zhang M, Liu Z, Wu C, Yuan H, Li YY, Zhao X, Lu H. A zinc finger HIT domain-containing protein, ZNHIT-1, interacts with orphan nuclear hormone receptor Rev-erbbeta and removes Rev-erbbeta-induced inhibition of apoCIII transcription. FEBS J. 2007; 274(20):5370-81.
13. Zhang M, Yang Y, Xu Y, Qie Y, Wang J, Zhu B, Wang Q, Jin R, Xu S, Wang H. Trehalose-6-phosphate Phosphatase from Mycobacterium tuberculosis Induces Humoral and Cellular Immune Responses. FEMS Immunol Med Microbiol. 2007; 49(1):68-74.
14. Zhang H, Wang J, Lei J, Zhang M, Yang Y, Chen Y, Wang H. PPE protein (Rv3425) from DNA segment RD11 of Mycobacterium tuberculosis: A potential B-cell antigen used for serological diagnosis and distinguish vaccinated controls from TB patients. Clin Microbiol Infect. 2007; 13(2):139-45.
15. Xu S, Yang Y, Jin R, Zhang M, Wang H. Purification and characterization of a functionally active Mycobacterium tuberculosis prephenate dehydrogenase. Protein Expr Purif. 2006; 49(2):151-8.
16. Yang Y, Zhang M, Zhang H, Lei J, Jin R, Xu S, Bao J, Zhang L, Wang H. Purification, characterization and structural study of Mycobacterium tuberculosis indole-3-glycerol phosphate synthase. Biochemistry (Mosc). 2006; 71 Suppl 1:S38-43.
17. Yang Y, Xu S, Zhang M, Jin R, Zhang L, Bao J, Wang H. Purifcation and characterization of a functionally active Mycobacterium tuberculosis pyrroline-5-carboxylate reductase. Protein Expr Purif. 2006; 45(1):241-8.
18. Zhang M, Yue J, Yang YP, Zhang HM, Lei JQ, Jin RL, Zhang XL, Wang HH. Detection of Mutations Associated with Isoniazid Resistance in Mycobacterium tuberculosis Isolates from China. J Clin Microbiol. 2005; 43(11):5477-82.
19. Zhang M, Wang JD, Li ZF, Xie J, Yang YP, Zhong Y, Wang HH. Expression and characterization of the carboxyl esterase Rv3487c from Mycobacterium tuberculosis. Protein Expr Purif. 2005; 42(1):59-66.
20. Gu X, Chen M, Wang Q, Zhang M, Wang B, Wang H. Expression and purification of a functionally active recombinant GDP-mannosyltransferase (PimA) from Mycobacterium tuberculosis H37Rv. Protein Expr Purif. 2005; 42(1):47-53.
Reviews and Book Chapter:
1. Turque O, Tsao T, Li T, Zhang M*. (2016) Translational Repression in Malaria Sporozoites. Microbial Cell. 3:189 – 231. (*corresponding author)
2. Zhang M*, Joyce BR, Sullivan WJ Jr., and Nussenzweig V. (2013) Translational Control in Plasmodium and Toxoplasma Parasites. Eukaryotic Cell. 12:161-167. (*corresponding author)
3. Goldberg DE, Zhang M, and Nussenzweig V. Chapter 6: Plasmodium eIF2α Kinases. Book: Protein Phosphorylation in Parasites: Novel Targets for Antiparasitic Intervention. (2013).