Microbiology and Immunology Discipline

Center for Cancer Cell Biology, Immunology, and Infection

Dr. Chang received his BS in 1965 from the Department of Entomology, National Taiwan University, Taipei, Taiwan, his M.A. in 1968 and his PhD in 1972 in cell biology/endosymbiosis from University of Guelph, Ontario, Canada. He was a postdoctoral fellow in parasitology at Rockefeller University in New York City from 1972 to 1974. He held the position of research associate from 1974 through 1976, assistant professor from 1976 to 1979, and associate professor from 1979 through 1983 at Rockefeller University.

He joined the faculty at Chicago Medical School in 1983 as professor of microbiology and immunology.

Research

Dr. Chang's main research interest is to develop strategies of treatment and prevention for infectious and non-infectious diseases through understanding molecular mechanisms of microbial virulence. Biological models studied include parasitic protozoa in mammalian cells and endosymbiotic bacteria in insects and protozoa.

His work, supported by NIH, has been focused on Leishmania model for microbial virulence. The key concept is the separation of invasive/evasive determinants responsible for infection and pathoantigenic determinants for immunopathology as the manifestation of the disease or virulence phenotype. Leishmania invasive/evasive determinants include enzymes, i.e. zinc protease/major surface glycoprotein (gp63), microsomal glycosyltransferase for protein glycosylation and nucleoside diphosphate kinase. Gp63 expression is regulated posttranslationally by N-glycosylation, which is in turn controlled by the glycosyltransferase gene expression. Secreted nucleoside diphosphate kinase is an evasive determinant to prevent ATP-induced P2X7-mediated apoptosis of macrophages. Other ongoing projects include genetic dissection of the unique metabolic defects, for example, in heme biosynthesis of trypanosomatid protozoa.

Dr. Chang's specific research interests include the following:

• Molecular Biology: Structure, regulation and expression of virulence and virulence-regulating genes studied by molecular genetic approach, i.e. gene replacement and transfection.
• Biochemistry: Purification and characterization of Leishmania gp63, microsomal N-acetylglucosamine-1-phosphate transferase and nucleoside diphosphate kinase.
• Cell Biology: Host-parasite cellular and molecular interactions.
• Applied Immunology: Oxidative photo-inactivation of Leishmania spp. for photodynamic vaccination and therapy.
• Molecular Epidemiology: Leishmania genotype-phenotype polymorphism in clinical pathology and epidemiology.

His long-term research interests further include:

• Evolution, application and function aspects of bacterial endosymbiosis.
• Regulation of Leishmania gene expression and vector designs.
• Development of photo-medicines for prophylaxis and therapy against infectious and malignant diseases.

Representative Publications

• Viana SM, Celes FS, Ramirez L, Kolli B, Ng DKP, Chang KP, de Oliveira CI. Photodynamic Vaccination of BALB/c Mice for Prophylaxis of Cutaneous Leishmaniasis Caused by Leishmania amazonensis. Front Microbiol. 2018 Feb 6;9:165. doi: 10.3389/fmicb.2018.00165. eCollection 2018. ()
• Chang, KP, Kolli BK, New Light group (2016) New "light" for one-world approach toward safe and effective control of animal diseases and insect vectors from leishmaniac perspectives. Parasit Vectors. 9:396.
• Lun ZR, Wu MS, Chen YF, Wang JY, Zhou XN, Liao LF, Chen JP, Chow LM, Chang KP. (2015) Visceral Leishmaniasis in China: an Endemic Disease under Control. Clin Microbiol Rev. 28:987-1004.
• Chang, KP. (2014) Vaccination for Disease Prevention and Control: The Necessity of Renewed Emphasis and New Approaches. J Immunol Immunotech. 1: 1-4.
• Chang, KP. (2013) Forward “Drug Resistance in Leishmania Parasites: Consequences, Molecular Mechanisms and Possible Treatments”, Ponte-Sucre, Alicia; Diaz, Emilia; Padrón-Nieves, Maritza (Eds.) XIV, Springer
• Dutta, S, Chang, C, Kolli, BK, Sassa, S, Yousef, Showe, M, Showe, L, and Chang, KP. (2012) Delta-aminolevulinate-induced host-parasite porphyric disparity for selective photolysis of transgenic Leishmania in the phagolysosomes of mononuclear phagocytes: A potential novel platform for vaccine delivery. Eukaryot Cell 11: 430-441.
• Chang, KP. (2012) Leishmaniases. In: Encyclopedia of Life Sciences, DOI: 10.1002/9780470015902.a0001954.pub3, John Wiley & Sons, Ltd.
• Kolli, BK, Costa, J, Chakrabarty, A. and Chang, KP. (2008) Leishmania release nucleoside diphosphate kinase to prevent ATP-dependent apoptosis of infected macrophages Mol Biochem Parasitol 158:163-75.
• Sah, JF, Ito, H., Kolli, BK, Peterson, DA, Sassa, S and Chang, KP. (2002) Genetic rescue of Leishmania deficiency in porphyrin biosynthesis creates mutants suitable for analysis of cellular events in uroporphyria and for photodynamic therapy. J. Biol. Chem. 277: 14902-14909.
• Kawazu, SI, Lu, HG, Chang, KP. (1997) Stage-independent splicing of transcripts from two heterlogous neighboring genes in Leishmania amazonensis. Gene 196: 49-59.
• Du, Yubin, McLaughlin, G, Chang, KP. (1994) 16S ribosomal DNA sequence identities of beta-proteobacterial endosymbionts in three Crithidia species. J. Bacteriol. 176: 3081-3084.
• Liu, Xuan and Chang, KP. (1992) The 63 kb circular amplicon of tunicamycin-resistant Leishmania contains a functional N-acetylglucosamine-1-phosphate transferase gene that can be used as a dominant selectable marker in transfection. Mol. Cell. Biol. 12: 4112-4122.
• Chang, KP, Chaudhuri, G, Fong D. (1990) Molecular determinants of Leishmania virulence. Ann Rev Microbiol. 44:499-529.
• Chang, CS and Chang, KP. (1986) Monoclonal antibody affinity purification of a leishmania membrane glycoprotein and its inhibition of leishmania-macrophage binding. Proc Nat Acad Sci USA 83: 100-104.
• Chang, KP, Bray, RS [Eds] (1985) Leishmaniasis, Elsevier Biomedical Press, Amsterdam, pp. 1-490.
• Wallach, M, Fong, D, Chang, KP. (1982) Post-transcriptional control of tubulin biosynthesis in leishmanial differentiation. Nature 299: 650-652.
• Chang, KP. (1980) Human cutaneous leishmania in a macrophage line: Propagation and isolation of intracellular parasite. Science 209: 1240-1242.
• Chang KP, Dwyer DM. (1976) Multiplication of a human parasite (Leishmania donovani) in phagolysosomes of hamster macrophages in vitro. Science 193:678-80.
• Chang, KP, Musgrave, AJ. (1972) Multiple Symbiosis in a leafhopper, Helochara communis fitch (Cicadellidae: Homoptera): envelopes, nucleoids and inclusions of the symbiotes. J. Cell Sci. 11: 275-293.