Kai Zhang

Professor

Biological Sciences

Email: kai.zhang@ttu.edu

Phone: 1(806) 834-0550

Office: Biology 205

Lab: Biology 203, 204

• Postdoc: Molecular Microbiology, Washington University School of Medicine, St. Louis, MO (2000-2006).
• Ph.D., Cellular and Microbial Biology, The Catholic University of America, Washington, DC. (2000)
• BSc., Biochemistry and Molecular Biology, Peking University, Beijing, China (1996)

Teaching:

• MBIO 3401: Principles of Microbiology (bio-major)
• MBIO 3400: Microbiology (non bio-major)
• MBIO4367/MBIO6367: Molecular Pathogenesis of  Protozoans (undergraduate/graduate, Communication Literacy Requirement)

Web Links:

• Leishmania Fact Sheet
• TriTryp DB

Research Interests

Protozoan parasites of the genus Leishmania alternate between extracelluar, flagellated promastigotes in sandfly vectors and intracellular, non-flagellated amastigotes residing in vertebrates. They are the causative agents for a group of devastating diseases (leishmaniasis) infecting 10-12 million people worldwide. Current drugs for leishmaniasis are plagued with low efficacy and high toxicity. With resistance on the rise and no safe vaccine available, there is a pressing need to maintain a steady stream of new drugs and drug targets. Our long term goal is to decipher the molecular strategy utilized by Leishmania parasites to thrive in the harsh environments in sandflies and mammals. Understanding the fundamental mechanism of pathogenesis can lead to new and improved treatments.

Leishmania parasites are easy to cultivate and highly amenable to genetic manipulations. My lab focuses on the role of lipid metabolism Leishmania pathogenesis. Lipids are essential components of life. They exert important functions in membrane biology, energy conservation, protein modification, and signal transduction. The role of lipids is relatively understudied in protozoan parasites. My group utilizes a combination of molecular biology, cell biology, animal models and lipidomic approaches to uncover the significance of sphingolipids, phospholipids, and sterols in Leishmania survival and virulence. A better understanding of lipid metabolism will not only advance our knowledge on the basic biology of Leishmania parasites, but also facilitate the development of novel drugs.

If you are interested in doing innovative research in Leishmania parasites as a postdoc, graduate student, or undergraduate student, please contact Dr. Kai Zhang for more information!

Selected Publications

• Basu S, Pawlowic MC, Hsu FF, Thomas G, Zhang K. Ethanolaminephosphate cytidylyltransferase is essential for survival, lipid homeostasis and stress tolerance in Leishmania major. PLoS Pathog. 2023 Jul 28;19(7):e1011112. doi: 10.1371/journal.ppat.1011112. [Epub ahead of print] PubMed PMID: 37506172.

• Haram CS, Moitra S, Keane R, Kuhlmann FM, Frankfater C, Hsu FF, Beverley SM, Zhang K, Keyel PA. The sphingolipids ceramide and inositol phosphorylceramide protect the Leishmania major membrane from sterol-specific toxins. J Biol Chem. 2023 Jun;299(6):104745. doi: 10.1016/j.jbc.2023.104745. Epub 2023 Apr 23. PubMed PMID: 37094699; PubMed Central PMCID: PMC10209034.

• Feng M, Jin Y, Yang S, Joachim AM, Ning Y, Mori-Quiroz LM, Fromm J, Perera C, Zhang K, Werbovetz KA, Wang MZ. Sterol profiling of Leishmania parasites using a new HPLC-tandem mass spectrometry-based method and antifungal azoles as chemical probes reveals a key intermediate sterol that supports a branched ergosterol biosynthetic pathway. Int J Parasitol Drugs Drug Resist. 2022 Dec;20:27-42. doi: 10.1016/j.ijpddr.2022.07.003. PubMed PMID: 35994895; PubMed Central PMCID: PMC9418051.

• Haram CS, Moitra S, Keane R, Breslav E, Zhang K, Keyel PA. Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins using Leishmania major. J Vis Exp. 2022 Oct 28;(188). doi: 10.3791/64341. PubMed PMID: 36373947.

• Okundaye B, Biyani N, Moitra S, Zhang K. The Golgi-localized sphingosine-1-phosphate phosphatase is indispensable for Leishmania major. Sci Rep. 2022 Sep 26;12(1):16064. doi: 10.1038/s41598-022-20249-w. PubMed PMID: 36163400; PubMed Central PMCID: PMC9513092.

• Zhang K. Balancing de novo synthesis and salvage of lipids by Leishmania amastigotes. Curr Opin Microbiol. 2021 Oct;63:98-103. doi: 10.1016/j.mib.2021.07.004. PubMed PMID: 34311265; PubMed Central PMCID: PMC8463422.

• Karamysheva ZN, Moitra S, Perez A, Mukherjee S, Tikhonova EB, Karamyshev AL, Zhang K. Unexpected Role of Sterol Synthesis in RNA Stability and Translation in Leishmania. Biomedicines. 2021 Jun 19;9(6). doi: 10.3390/biomedicines9060696. PubMed PMID: 34205466; PubMed Central PMCID: PMC8235615.

• Gutierrez Guarnizo SA, Tikhonova EB, Zabet-Moghaddam M, Zhang K, Muskus C, Karamyshev AL, Karamysheva ZN. Drug-Induced Lipid Remodeling in Leishmania Parasites. Microorganisms. 2021 Apr 9;9(4). doi: 10.3390/microorganisms9040790. PubMed PMID: 33918954; PubMed Central PMCID: PMC8068835.

• Moitra S, Basu S, Pawlowic M, Hsu F, Zhang K. De novo synthesis of phosphatidylcholine is essential for the promastigote but not amastigote stage in Leishmania major. Frontiers in Cellular and Infection Microbiology. 2021 March 2021. https://doi.org/10.3389/fcimb.2021.647870. PubMed Central PMCID: PMC7996062.

• Zhang K, Hsu F. Shotgun Lipidomic Analysis of Leishmania Cells. Methods Mol Biol. 2021;2306:215-225. doi: 10.1007/978-1-0716-1410-5_14. PubMed PMID: 33954949.

• Mukherjee S, Moitra S, Xu W, Hernandez V, and Zhang K. (2020) Sterol 14α-demethylase is vital for mitochondrial functions and stress tolerance in Leishmania major. PLoS Pathogens. 16(8):e1008810. doi: 10.1371/journal.ppat.1008810. PubMed Central PMCID: PMC7462297.

• Ning, Y, Frankfater C, Hsu F, Soares RP, Cardoso CA, Nogueira PM, Lander NM, Docampo R, and Zhang K. (2020) Lathosterol oxidase (sterol C5-desaturase) deletion confers resistance to amphotericin B and sensitivity to acidic stress in Leishmania major. mSphere 2020 Jul 1;5(4). doi: 10.1128/mSphere.00380-20. PMCID: PMC7333571.

• Zhang, K., and Beverley, S. M. (2019) Mannogen-ing central carbon metabolism by Leishmania. Trends in Parasitology. pii: S1471-4922(19)30243-0. doi: 10.1016/j.pt.2019.10.001. PubMed Central PMCID: PMC8018590.
• Moitra, S., Pawlowic, M. C., Hsu, F.F., and Zhang, K. (2019) Phosphatidylcholine synthesis through cholinephosphate cytidylyltransferase is dispensable in Leishmania major. Sci. Rep. 9(1):7602. doi: 10.1038/s41598-019-44086-6. PMCID: PMC6527706.
• Mukherjee, S., Basu, S., and Zhang, K. (2019) Farnesyl pyrophosphate synthase is essential for the promastigote and amastigote stages in Leishmania major. Mol Biochem Parasitol. 230:8-15. PMCID: PMC6529949.
• Mukherjee, S., Xu, W., Hsu, F. F., Patel, J., Huang, J., and Zhang, K. (2019) Sterol methyltransferase is required for optimal mitochondrial function and virulence in Leishmania major. Mol. Microbiol.111(1):65-81. PMCID: PMC6351164.
• Karamysheva, Z. N., Tikhonova, E. B., Grozdanov, P. N.,  Huffman, J. C., Baca, K. R., Karamyshev, A., Denison, R. B., MacDonald, C. C., Zhang, K., and Karamyshev, A. L. (2018) Polysome Profiling in Leishmania, Human Cells and Mouse Testis. JVoE. (134). doi: 10.3791/57600. doi: 10.3791/57600. PMCID: PMC5933418.
• Xu, W., Mukherjee, S., Ning, Y., Hsu, F. F., Baykal, E., Huang, J., and Zhang, K. (2018) Cyclopropane fatty acid synthesis affects cell shape and acid resistance in Leishmania mexicana. Int. J. Parasitol. 48(3-4):245-256. PMCID: PMC5844833.
• Pawlowic, M. C., Hsu, F.F., Moitra, S., Biyani, N., and Zhang, K. (2016) Plasmenylethanolamine synthesis in Leishmania major.Mol. Microbiol.101(2):238-49. PMCID: PMC4935589.
• Xu, W., Hsu, F. F., Baykal, E., Huang, J., and Zhang, K. (2014) Sterol biosynthesis is required for heat resistance but notextracellular survival in Leishmania. PLoS Pathogens. 10(10):e1004427. PMCID: PMC4207814.
• Zhang, O., Hsu, F. F., Xu, W., Pawlowic, M.C., and Zhang, K. (2013) Sphingosine kinase A is a pleiotropic and essential enzyme for Leishmania survival and virulence. Mol. Microbiol. 90(3):489-501. PMCID: PMC3938578.
• Pillai, A. B., Xu, W., Zhang, O., and Zhang,K. (2012) Sphingolipid Degradation in Leishmania (Leishmania) amazonensis. PLoS Negl Trop Dis. 6(12):e1944. PMCID: PMC3527339.
• Pawlowic, M. C., and Zhang, K. (2012) Leishmania parasites possess a platelet-activating factor acetylhydrolase important for virulence. Mol Biochem Parasitol. PMCID: PMC3492548.
• Zhang, O, Xu, W., Pillai, A., and Zhang, K. (2012) Developmentally Regulated Sphingolipid Degradation in Leishmania major. PLoS One. 7(1):e31059. PMCID: PMC3267774. 
• Xu, W., Xin, L., Soong, L., and Zhang, K. (2011)Sphingolipid degradation by Leishmania is required for its resistance to acidic pH in the mammalian host. Infect Immun. 79(8):3377-87.PMCID: PMC3147570. 
• Zhang, K., and Beverley, S. M. (2010) Phospholipid and sphingolipid metabolism in Leishmania.Mol. Biochem. Parasitol. 170(2):55-64. PMCID: PMC2815228.
• Zhang, K., Bangs, J. D., and Beverley, S.M. (2010) Sphingolipids in parasitic protozoa. Adv Exp MedBiol. 688:238-48. PMCID: PMC2951629. 
• Zhang, O., Wilson, M. C., Xu, W., Hsu, F.F., Turk, J., Kuhlmann, F. M., Wang, Y., Soong, L., Key, P., Beverley, S. M.,and Zhang, K. (2009) Degradation of Host Sphingomyelin Is Essential for Leishmania Virulence. PLoS Pathogens 5(12): e1000692.doi:10.1371/journal.ppat.1000692. PMCID: PMC2784226.
• Sutterwala, S. S., Hsu, F. F., Sevova, E.S.,Schwartz, K. J., Zhang, K., Key, P., Turk, J., Beverley, S. M., and Bangs,J.D. (2008) Developmentally Regulated Sphingolipid Synthesis in African Trypanosomes.Mol. Microbiol. 70(2):281-296. PMCID: PMC2629665.
• Hsu, F. F., Turk, J., Zhang, K., and Beverley,S. M. (2007) Characterization of Inositol Phosphorylceramides from Leishmania major by Tandem Mass Spectrometry with Electrospray Ionization.J Am Soc Mass Spectrom 18(9):1591-604. PMCID: PMC2065762. 
• Zhang, K., Pompey, J. M, Hsu, F.F., Key, P.,B and Bandhuvula P., Saba, J. D., Turk, J., and Beverley, S. M. (2007) Redirection of sphingolipid metabolism towards de novo synthesis of ethanolamine in the protozoan parasite Leishmania major. EMBOJ 26:1094-1104. PMCID: PMC1852826.
• Zhang, K., Hsu, F. F., Scott, D. A., Docampo,R., Turk, J., and Beverley, S. M. (2005) Leishmania salvage and remodeling of host sphingolipids in amastigote survival and acidocalcisome biogenesis. Mol.Microbiol.55(5): 1566-78. PMCID: PMC3803142.
• Zhang, K., Barron, T., Turco, S. J., and Beverley,S. M. (2004) The LPG1 gene family of Leishmania major. Mol. Biochem. Parasitol.136(1):11-23. PMCID: PMC3791616.
• Zhang, K., Showalter, M., Revollo, J., Hsu,F.F., Turk, J., and Beverley, S. M. (2003) Sphingolipids are essential for differentiation but not growth in Leishmania. EMBOJ 22:6016-6026. PMCID: PMC275442.
• Descoteaux, A., Avila, H. A.,Zhang, K.,Turco,S. J., and Beverley, S. M. (2002) Leishmania LPG3 encodes a GRP94 homolog required for phosphoglycan synthesis implicated in parasite virulence but not viability. EMBO J 21: 4458-69. PMCID: PMC126187.
• Zhang, K., and Rathod, P. K. (2002) Divergent regulation of dihydrofolate reductase between malaria parasite and human host. Science 296:545-7. PMCID:PMC3830934.
• Shallom, S., Zhang, K., Jiang, L., and Rathod,P. K. (1999) Essential protein-protein interactions between Plasmodium falciparum thymidylate synthase and dihydrofolate reductase domains. J Biol Chem.274(53):37781-6. PMCID: PMC3791593.