Dr. Chang received his B.S. in 1965 from the National Taiwan University, Taipei, Taiwan, a M.A. in 1968 and Ph.D. in 1972 in Cell Biology from the University of Guelph, Ontario, Canada. He was a Postdoctoral Fellow in Parasitology at Rockefeller University in New York, NY 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 the current university in 1983 as Professor of Microbiology and Immunology.
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: (1) Molecular Biology
: Structure, regulation and expression of virulence and virulence-regulating genes studied by molecular genetic approach, i.e. gene replacement and transfection; (2) Biochemistry
: Purification and characterization of Leishmania
gp63, microsomal N-acetylglucosamine-1-phosphate transferase and nucleoside diphosphate kniase; (3) Cell Biology
: Host-parasite cellular and molecular interactions;
(4) Molecular Immunology
: Porphyric Leishmania
spp. as inducible suicidal mutants for photodynamic vaccination and therapy; and (5) Molecular Epidemiology
genotype-phenotypec polymorphism in clinical pathology and epidemiology.
His long-term research interests further include: (1) Evolution, application and function aspects of bacterial endosymbiosis; (2) Regulation of Leishmania
gene expression and vector designs; and (3) Development of porphyric Leishmania
as a universal platform for photodynamic vaccinations and therapy.
Kumari, S., Samant, M., Khare, P., Misra, P., Dutta, S., Kolli, B.K., Sharma, S., Chang, KP and Dube, A. (2009) Photodynamic vaccination of hamsters with inducible suicidal mutants of Leishmania amazonensis elicits T cell-transferable immunity against visceral leishmaniasis. Eup J. Immunol. 38:1-14.
Dutta, S., Sassa, S., Chang, K.-P. (2008) Leishmania spp.:Delta-aminolevulinate-inducible porphyria by genetic complementation of incomplete heme biosynthesis. Exp Parasitol 118: 629-36.
Dutta, S., Kolli, BK, Tang, A., Sassa, S. and Chang, K.-P. (2008) Transgenic Leishmania model for delta-aminolevulinate-inducible monospecific uroporphyria: Cytolytic phototoxicity initiated by singlet oxygen-mediated inactivation of proteins and its ablation by endosomal mobilization of cytosolic uroporphyrin. Eukaryot. Cell 7: 1146-1157.
Sanjay R. Mehta, Robert Huang, Meng Yang, Xing-Quan Zhang, Bala Kolli, Kwang-Poo Chang, Robert M. Hoffman, Yasuyuki Goto, Roberto Badaro and Robert T. Schooley (2008) Real-Time Vivo Green Fluorescent Protein Imaging of a MurineLeishmaniasis Model as a New Tool for Leishmania Vaccine and Drug Discovery. Clin. Vaccine Immunol. 15, 1764-1770.
Kolli, B.K., Costa, J, Chakrabarty, A. and Chang, K.-P. (2008) Leishmania release nucleoside diphosphate kinase to prevent ATP-dependent apoptosis of infected macrophages. Mol. Biochem. Parasitol. 158:163-175.
Waki, K., Dutta, S., Ray, D., Kolli, B., Kawazu, S.I., Lin, C.-P. and Chang, K.-P. (2007) Transmembrane molecules for phylogenetic analysis of pathogenic protists: Leishmania-specific informative sites in hydrophilic loops of trans-ER N-acetylglucosamine-1-phosphate transferase.
karyot. Cell 6: 198-210.
Sah, J.F., Ito, H., Kolli, B.K., Peterson, D.A., Sassa, S. and Chang, K.-P. (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.
Chen, D.Q., Kolli, B.K., Yadava, N., Lu, H.G., Gilman-Sachs, A., Peterson, D.A. and Chang K.-P. (2000) Episomal expression of specific sense and antisense mRNAs in Leishmania amazonensis: modulation of gp63 level in promastigotes and their infection of macrophages in vitro, Infect. Immun., 68:80-86.
McGwire, B.S. and Chang, K.-P. (1996) Posttranslational regulation of a Leishmania HEXXH metalloproteinase (gp63). The effects of site-specific mutagenesis of catalytic, zinc-binding, N-glycosylation and GPI-addition sites on N-terminal end cleavage, intracellular stability and extracellular exit. J. Biol. Chem. 271: 7903-7909.
Du, Y., Maslov, D.A. and Chang, K.-P. (1994) Monophyletic origin of ß-division proteobacterial endosymbionts and their coevolution with insect trypanosomatid protozoa Blastocrithidia culicis and Crithidia spp. Proc. Natl. Acad. Sci. USA 91: 8437-8441.
Liu, Xuan and Chang, K.-P. (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.
Detke, S., Chaudhuri, G., Kink, J.A., and Chang, K.-P. (1988) DNA amplification in tunicamycin-resistant Leishmania mexicana amazonensis. Multiple copies of a single 63 Kilobase supercoiled molecule. J. Biol. Chem. 263: 3418-24.
Kink, J.A. and Chang, K.-P. (1987) Tunicamycin-resistant Leishmania mexicana: Virulent phenotype associated with increased N-acetylglucosamine-1-phosphate transferase activity and amplification of its gene. Proc. Nat. Acad. Sci. USA 84: 1253-1257.
Chang, C.S. and Chang, K.-P. (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.