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Dr. Chang joined the Cornell Faculty in 1989 and is a member of the graduate fields of comparative biomedical Sciences and Zoology. He participates in the infection and pathobiology Program and in the Cornell Genomics Initiative. His research program focuses on the molecular pathogenesis of bacterial diseases and his formal teaching activity has been mainly in the graduate special topics in infectious disease (VETDL 702) and undergraduate course (Bio. Sci.499).
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| Research Interests |
| Research interest include molecular biology of infectious disease; DNA and recombinant subunit vaccine development; molecular basis of bacterial pathogenesis; immunopathology of infectious disease; molecular diagnosis of infectious diseases; host defense mechanisms; comparative genomics and proteomics. My research focuses on both basic and applied aspects. My research interest is to understand the mechanisms of infection and concurrently develop an effective vaccine to prevent the infection of the pathogens such as M. avium subsp. paratubercuosis, Leptospira and Salmonella. Paratuberculosis (Johne's Disease) occurs worldwide as a chronic granulomatous enteritis of domestic and wild ruminants. The infection is caused by M. avium subsp. paratubercuosis, which shares 98% genomic homology with M. avium but contains an insertion sequence, IS900, which distinguishes it from M. avium. The disease is characterized clinically by intermittent but persistent diarrhea (in cattle), progressive weight loss, and eventually, death. Presently, the disease is untreatable. Our long goal is to develop a cocktail recombinant/DNA vaccine for the prevention of paratuberculosis infection. Research in our laboratory focuses on the identification of virulence factors of this organism. We have cloned and expressed some of the virulence factor genes, such as 85 complex (A, B, & C genes), 35-kDa protein, SOD, ESAT-6, thiolperoxidase and also specific genes of partuberculosis such as mptC and mptD. Leptospirosis in livestock is caused by the spirochete belonging to the genus Leptospira and is manifested by various syndromes such as chronic interstitial nephritis, mastitis, myocarditis and hemolytic crisis. Leptospirosis is identified as one of the emerging infectious diseases, exemplified by recent large outbreaks in several countries. We are the first group to identify Lig ( Leptospiral Immuno Globulin-like protein encoded by ligA, B and C) proteins, which are specifically induced during leptospiral infection. Our basic studies are to identify the virulence factors and their mechanism of infection. Our applied study is to develop a recombinant proteins/DNA cocktail vaccine against this disease. In cooperation with Dr. Bruce Roe from the University of Oklahoma, the complete genomic DNA sequences of serovar Pomona and Grippotyphosa are in progress. With the available genome sequences, we have cloned and expressed several outer membrane proteins of Leptospira. Further vaccination trails using these recombinant proteins are in progress. Salmonellosis is one of the leading causes of food borne disease in United States. Out of 1500 serovars of Salmonella , Typhimurium, Dublin and Cholerasuis are the predominant serovars in animals in United States. Infection in animals usually leads to gastroenteritis but the bacteria can also survive asymptomatically resulting in a potentially serious problem for both the livestock industry and public health. Both live and killed vaccines developed so far are not effective and produced side effects. Therefore, a safe and effective attenuated vaccine is indispensable. Attempts to target the in vivo genes crucial for the survival of Salmonella using signature tagged mutagenesis of Chloreasuis in the natural host resulted in mutants targeting type III secretion systems, lysogens and unknown genes. We are also studying the transcriptomics profiles of in vitro and in vivo grown salmonella using microarray. Research to develop a molecular diagnosis (microarray) of bacterial pathogens is funded by NIH-ZRU program. We focus on E. coli and Salmonella in our initial study. Categories of pathogenic E. coli focused for developing array are enterohaemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), uropathogenic E. coli (UPEC), enteroaggregative E. coli (EAEC) and neonatal meningitis E. coli (NMEC). Non-pathogenic E. coli is included to rule out the possible contamination. We have targeted both virulence genes and specific genes of each category for the development of multi-pathogen detection array. As to Salmonella, we focused on subspecies I of Salmonella for developing array system for diagnosis because this is the only Salmonella group that causes disease in warm-blooded animals. Based on the comparative data of genomic sequences of different serovars of salmonella, the core genes and variable genes of Salmonella have been selected for the study. |
| Education |
| DVM | - 1974 | National Pingtung Institute of Agriculture, Taiwan (Veterinary Medicine) | |||
| M.S. | - 1981 | University of Idaho, Moscow, Idaho (Immunology/Pathology) | |||
| Ph.D. | - 1984 | Texas A&M University, College Station, Texas (Microbiology/Immunology) | |||
| Postdoc | - 1984-1989 | Texas A&M University, College Station, Texas (Molecular Biology) |
| Research and Professional Experience |
| 1974-1979 | Assistant Pathologist, Veterinary Pathology Division, Taiwan Provincial Research Institute for Animal Health, Taipei, Taiwan | ||||
| 1979-1981 | Research Assistant and Graduate Student, Department of Veterinary Science, University of Idaho, Moscow, Idaho | ||||
| 1981-1984 | Research Assistant and Graduate Student, Department of Veterinary Microbiology and Parasitology, College of Veterinary Medicine, Texas A&M University, College Station, Texas | ||||
| 1984-1985 | Research Associate, Department of Medical Biochemistry and Genetics, College of Medicine, Texas A&M University, College Station, Texas | ||||
| 1986-1989 | Assistant Research Scientist, Department of Medical Biochemistry and Genetics, College of Medicine, and Department of Biochemistry and Biophysics, College of Agriculture & Life Science, Texas A&M University, College Station, Texas | ||||
| 1989-1996 | Assistant Professor and Assistant Director of the Microbiology Section, Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, New York | ||||
| 1996-2002 | Associate Professor and Assistant Director of the Microbiology Section, Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York | ||||
| 2003 Jan - Jul |
Visiting Professor, Department of Infectious disease and Medicine, College of Medicine, Stanford University. Stanford, California | ||||
| 2003-present | Professor, Department of Population Medicine & Diagnostic Sciences, and Director of infectious disease program, New York State Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, New York |
| Honors and Awards |
| Beta Rho Chapter of Phi Sigma National Honor Society |
| Diplomate of the American College of Veterinary Microbiologist |
| The Society of Phi Zeta |
| Who's Who in America? |
| Won second prize for a paper from the American Lyme Disease Association, 1997 |
| Professional Society Memberships |
| American Association for the Advancement of Science | |||||
| American Association of Veterinary Laboratory Diagnosticians | |||||
| American Leptospirosis Research Conference, Inc. | |||||
| American Society for Microbiology | |||||
| American College of Veterinary Microbiologist | |||||
| Conference of Research Workers in Animal Diseases | |||||
| International Leptospirosis Society | |||||
| New York State Veterinary Society | |||||
| Society of Sigma Xi | |||||
| The Society of Phi Zeta | |||||
| United States Animal Health Association | |||||
| AALVD Enteric Disease Committee, 1991-present | |||||
| Editor, Journal of Korea Veterinary Medicine, 2001-present | |||||
| Member of College Library Committee, 1996-present | |||||
| Treasure, American Leptospirosis Research Conference, Inc., 2001-present | |||||
| USAHA/AAVLD Committee on Foreign and Emerging Diseases, 1998-present | |||||
| USAHA/AAVLD Committee on Johne's Disease, 1998-present | |||||
| Adviser, Cornell Taiwanese Student Association (Graduate students), 1996-present | |||||
| Selected Publications |
- Chang, Y. F., R. Young., D. Post, and D. K. Struck. 1987. Identification and characterization of the Pasteurella haemolytica leukotoxin. Infect. Immun. 55: 2348-2354.
- Chang, Y. F., R. Young, T. L. Moulds, and D. K. Struck. 1989. Secretion of the Pasteurella leukotoxin by E. coli. FEMS Microbial. Let. 60: 169-174.
- Chang, Y. F., R. Young, and D. K. Struck. 1989. Cloning and characterization of a hemolysin gene from Actinobacillus (Haemophilus) pleuropneumoniae DNA &Cell biology: 8: 635-647.
- Cruz, W.T., R. Young, Y. F. Chang, and D.K. Struck. 1990. Deletion analysis resolves cell-binding and lytic domains of the Pasteurella leukotoxin. Mol. Microbiol. 4: 1933-1939.
- Chang, Y. F., R. Young, and D.K. Struck. 1991. The Actinobacillus pleuropneumoniae determinant: unlinked appCA and appBD loci flanked by pseudogenes. J. Bacteriol. 173: 5151-5158.
- McWhinney, D.R., Y. F. Chang, R.Young, and D. K.Struck. 1992 Separable domains define target cell specificities of the RTX hemolysin from Actinobacillus pleuropneumoniae. J. Bacteriol. 174: 291-297.
- Appel, M. J.G., S. Allan, R. H. Jacobson, T.L. Lauderdale, Y. F. Chang, S. J. Shin, J. Thomford, R. Todhunter, and B. A. Summers. 1993. Experimental Lyme disease in dogs produced arthritis and persistent infection. J. Infect. Dis. 167: 651-664.
- Chang, Y. F., D. P. Ma, J. Shi, and M. M. Chengappa. 1993. Molecular characterization of a leukotoxin gene from a Pasteurella haemolytica-like organism, encoding a new member of RTX family. Infect. Immun. 61: 2089-2095.
- Chang, Y. F., J. Shi, D. P. Ma, S. J. Shin, and D. H. Lein. 1993. Molecular analysis of the Actinobacillus pleuropneumoniae RTX toxin-III gene cluster. DNA. Cell Biol. 12: 351-362.
- Chang, Y. F., T. L. Lauderdale, W. Y. Lee, S. J. Shin, R. H. Jacobson, M. J. Appel, and D. H. Lein. 1993. Expression and secretion of outer surface protein (OspA) of Borrelia burgdorferi from E. coli. FEMS Microbiol. Lett. 109: 297-302.
- Frey, J., J. T. Bosse, Y. F. Chang, J.M. Cullen, B. Fenwick, G.F. Gerlach, D. Gygi, F. Haesebrouck, T. J. Inzana, R. Jansen, E. M. Kamp, J. Macdonald, J. I. MacInnes, K.R. Mittal, J. Nicolet, A.N. Rycroft, R.P.A.M. Segers, M.A. Smits, E. Stenbaek, D.K. Struck, J. F. Van Den Bosch, P. J. Wilson and R. Young. 1993. Actinobacillus pleuropneumoniae RTX-toxins: Uniform designation of hemolysins, cytolysins, pleurotoxin and their genes. J. Gen. Microbiol. 139: 1723-1728.
- Chang, Y. F., M. J. Appel, R. H. Jacobson, S. J. Shin, P. Harpending, R. Straubinger, L. A. Patrican, H. Mohammed, and B. A. Summers. 1995. Recombinant OspA protects dogs against infection and disease caused by Borrelia burgdorferi. Infect. Immun. 63: 3543-3549.
- Straubinger, R. K., Y. F. Chang, R. H. Jacobson, and M. J. G. Appel. 1995. Protection against Lyme disease: Sera from vaccinated dogs, but not from tick infected dogs, inhibit the in vitro growth of Borrelia burgdorferi. J. Clin. Microbiol. 33: 2745-2751.
- Chang, Y. F., R. Straubinger, R. H. Jacobson, J. B. Kim, T. J. Kim, D. Kim, S. J. Shin, and M. J. G. Appel. 1996. Dissemination of Borrelia burdorferi after experimental infection in dogs. J. Spiro. Tick-Borne Dis. 3: 80-86.
- Straubinger, R. K., A. F. Straubinger, L. Harter, R. H. Jacobson, Y. F. Chang, B. A. Summers, H. N. Erb, and M. J. G. Appel. 1997. Borrelia burgdorferi migration and proliferation causes up-regulation of interleukin-8 in synovial membranes of experimentally infected dogs. Infect. Immun. 65: 1273-1285.
- McDonough P. L., R. H. Jacobson, J. F. Timoney, A. Mutalib, D. C. Kradel, Y. F. Chang, S. J. Shin, D. H. Lein, S. Trock, and K. Wheeler. 1998. Interpretations of antibody responses to Salmonella enterica serotype Enteritidis gm flagellin in poultry flocks are enhanced by a Kinetics-based enzyme-linked immunosorbent assay. Clin. Diagn. Lab. Immunol. 5: 550-555.
- Chang, Y. F., V. Novosel, S. P. McDonough, R. H. Jacobson, C. F. Chang, T. Divers, F. W. Quimby, S. Shin, and D. H. Lein. 1999. Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer surface protein A (OspA) in horses. Vaccine 18: 540-548.
- Chang, Y. F.,S. P. McDonough, K.S. Shin, C. F. Chang, and T. Divers. 2000. Human granulocytic ehrlichiosis agent (HGE) infection in a pony vaccinated with recombinant OspA vaccine and challenged by exposure to naturally infected ticks. Clin. Diag. Lab. Immunol. 7: 68-71.
- Simpson, K.W., D. Strauss-Ayali, E. Scanziani, R. K. Straubinger, P. L. McDonough, A.F. Straubinger, Y. F. Chang, C. Domeneghini, N. Arebi, and J. Calm. 2000. Helicobacter felis infection is associated with lymphpoid follicular hyperplasia and mild gastritis but normal gastric secretory function in cats. Infect. Immun. 68: 779-790.
- Simpson, K.W., D. Strauss-Ayali, E. Scanziani, R. K. Straubinger, P. L. McDonough, A. F. Straubinger, Y. F. Chang, M. Esteves, J. G. Fox, C. Domeneghini, N. Arebi, and J. Calam. 2001. Gastric secretory function in cats with Helicobacter pylori infection. Helicobacter 6: 1-14.
- Raghavan, P. U. M., Y. F. Chang, S. S. D. Jusuf, S. Artiushin, J. F. Timoney, S. P. McDonough, S. C. Barr, T. J. Divers, P. McDonough, K. W. Simpson, and H. Mohammed. 2002. Cloning and molecular characterization of an immunogenic LigA of Leptospira interrogans. Infect. Immun. 70:5924-5930.
- Dheenadhayalan, V., K. S. Shin, C. F.Chang, C. D. Chang, S. J. Wang, S. P. McDonough, P. L. McDonough, S. Shin, A. Torres, and Y. F. Chang. 2002. Cloning and characterization of the genes coding for antigen 85A, 85B and 85C of Mycobacterium avium subsp. paratuberculosis. DNA Seq. 13:287-294.
- Teng, C.H., R. U.M. Palaniappan, and Y. F. Chang. 2003. Cloning and characterization of an Ehrlichia canis gene encoding a protein localized to the morula membrane. Infect. Immun. 71:2218-2225.
- Hsu, Y.M., N. Chin, C. F. Chang, Y. F. Chang. 2003. Cloning and characterization of the Actinobacillus pleuropneumoniae fur gene and its role in regulation of ApxI and AFUABC expression. DNA seq. 14:169-181.
- Santos, L. R. D., S. M. Barrouin-Melo, Y. F. Chang, J. Olson, S. P. McDonough, F. Quimby, W. L. C. D. Santos, L. C. Pontes-de-Carvalho, G. G. Oliveria. 2003. Recombinant single-chain interleukin-12 induces interferon mRNA expression in peripheral blood mononuclear cells of dogs with visceral leishmaniasis. Vet. Immun. Immunopathol. 98:43-48.
- Palaniappan, R. U., Y. F. Chang, F. Hassan, S.P. McDonough, M. Pough, S.C. Barr, K. W. Simpson, H. O. Mohammed, S. Shin, P. McDonough, R. Zuerner, J. Qu, & B. Roe. 2004. Expression of leptospiral immunoglobulin-like protein from Leptospiral interrogans and evaluation of its diagnostic potential in kinetic enzyme linked immunosorbent assay. J. Med. Microbiol. 53: 975-84.
- Wang, Z., Z. Yuan, M. Matsumoto, U. R. Hengge and Y. F. Chang. 2005. Immune responses with DNA vaccines encoded different gene fragments of severe acute respiratory syndrome coronavirus in BALB/c mice. BioChem. BioPhy. Res. Com. 327:130-135.
- Palaniappan, R. U., Y. F. Chang, C. F. Chang, M. J. Pan, C. W. Yang, P. Harpending, S. P. McDonough, E. Dubovi, J. Qu, B. Roe and T. Divers. 2005. Evaluation of lig-based conventional and real time PCR for the detection of pathogenic leptospires. Mol. and Cell. Probes. 19:111-117.
- Hsieh, W.J., Y.F. Chang, C. S. Chen, and M. J. Pan. 2005. Omp52 is a growth-phase-regulated outer membrane protein of Leptospira santarosai serovar Shermani. FEMS Microbiol. Let. 243:339-345.
- Shin, S.J., C.F. Chang, C. C. Chang, S. P. McDonough, B. Thompson, H.S. Yoo, and Y. F. Chang. 2005. In vitro cellular immune response to recombinant antigens of Mycobacterium avium subsp. paratuberculosis. Infect. Immun. 73:5074-5085.
- Ku, Y.W., S. P. McDonough, R.U.M. Palaniappan, C. F. Chang, Y. F. Chang. 2005. Identification and characterization of in vivo attenuated mutants of Salmonella enterica serovar Choleraesuis using signature-tagged mutagenesis in a pig infection model. Infect. Immun. 73:8194-8203.
- Raghavan, P. U. M., S. P. McDonough, T. J. Divers, C. S. Chen, M.J. Pan, M. Matsumoto and Y. F. Chang. 2006. Immunoprotection of recombinant leptospiral immunoglobulin like A protein (LigA) against Leptospira interrogans serovar Pomona infection. Infect. Immun. 74:1745-1750.
- Palaniappan, R. U., Y. Zhang, D. Chiu, A. Torres, C. DebRoy, T. S. Whittam and Y. F. Chang. 2006. Differentiation of Escherichia coli pathotypes by oligonucleotide spotted array. J. Clin. Microbiol. 44:1495-1501.
- Palaniappan, R. U., S. Ramanujam and Y. F. Chang. 2007. Leptospirosis: Pathogenesis, Immunity, and Diagnosis. Current Opinion Infect. Dis. 20:284-292.
- Lin, Y.P. and Y. F. Chang. 2007. A domain of the Leptospira LigB contributes to high binding of fibronectin. Biochem. Biophy. Res. Comm. 362:443-448.
- Chang, Y.F., C. S. Chen, R. U.M. Palaniappan, S. P. McDonough, W. Yang, M. J. Pan, and C. F. Chang. 2007. Immunogenicity and protection of the recombinant leptospiral immunogenic proteins as vaccine candidates. Vaccine 25: 8190-8197.
- Yu, C.Y., S. J. chou, C. M. Yeh, M.R. Chao, K. C. Huang, Y. F. Chang, C. S. Chiou, F. X. Weill, C. H. Chiu, C. H. Chu, and C. S. Chu. 2007. Prevalence and characterization of multidrug-resistant (ACSSuT) Salmonella enterica serovar Typhimurium isolated from our Gosling’s farms and a hatchery farm. J. Clin. Microbiol. 46:522-526.
- Faisal, S.M., W. Yan, C. S. Chen, R. U.M. Palaniappan, S. P. McDonough, and Y. F. Chang. 2008. Evaluation of protective immunity of Leptospira immunoglobulin like protein A (LigA) DNA vaccine against challenge in hamsters. Vaccine, 26:277-287.
- Chen, L. H., K. Kathaperumal, C. J. Huang, S. P. McDonough, S. Stehman, B. Akey, J. Huntley, C.F. Chang and Y. F. Chang. 2008. Immune responses in mice to Mycobacterium avium subsp. paratuberculosis following vaccination with a novel 74F recombinant polyprotien. Vaccine 26:1253-1262.
- Kathaperumal, K., S. U. Park, S. P. McDonough, S. Stehman, B. Akey, J. Huntley, S. Wong, L. H. Chen, C.-F. Chang and Y. F. Chang. 2008. Vaccination with recombinant Mycobacterium avium subsp. paratuberculosis proteins induces differential immune responses and protects calves against infection by oral challenge. Vaccine, 26:1652-1663.
- Lin, Y.P. and Y. F. Chang. 2008. The C-terminal variable domain of LigB from Leptospira mediates binding to fibronectin. J. Vet. Sci. 9:133-144.
- Scaria, S., P. U. M. Palaniappan, D. Chiu, J.A. Phan, L. Ponnala, P. McDonough, Y. T. Grohn, S. Porwollik, M. McClelland, C.S. Chiou, C. Chu and Y. F. Chang. 2008. Microarray for molecular typing of Salmonella enterica serovars. Mol. Cell. Probes 22:238-243.
- Park, S.U., K. Kathaperumal, S. McDonough, B. Akey, J. Huntley, J. P. Bannantine and Y.F. Chang. 2008. Immunization with a DNA vaccine cocktail induces a Th1 response and protects mice against Mycobacterium avium subsp. paratuberculosis. Vaccine. 26:4329-4337.
- Lin, Y.P. R. Raman, Y. Sharma, and Y. F. Chang. 2008. Calcium binds to Leptospiral immunoglobulin-like protein, LigB and modulates fibronectin-binding. J. Biol. Chem. 283(12): 25140-25149.
- Scaria, J., A. Sreedharan, and Y. F. Chang. 2008. Microbial Diagnostic Array Workstation (MDAW): A web server for diagnostic array data storage, sharing and analysis. Source Code Biol. Med. 3:14-18.
- Kathaperumal, K,, V. Kumanan, S. McDonough, L. H. Chen, S. U. Park, M. A. Moreira, B. Akey, J. Huntley, C. F. Chang, and Y. F. Chang 2009. Evaluation of immune responses and protective efficacy in a goat model following immunization with a coctail of recombinant antigens and a polyprotein of Mycobacterium avium subsp. paratuberculosis. Vaccine 27:123-135.
- Faisal, S.M., W. Yan, S. P. McDonough, and Y. F. Chang 2009. Leptospira immunoglobulin-like protein A variable region (LigAvar) incorporated in Liposomes and PLGA-Microspheres produces a robust immune response correlating to protective immunity. Vaccine 27:378-387.
- Yan, W., S. M. Faisal, S. P. McDonough, T. J. Divers, S. C. Barr, M. J. Pan, C. F. Chang and Y.F. Chang. 2009. Recombinant Leptospira Immunoglobulin-Like Protein B (rLigB) protects hamsters against lethal Leptospira interrogans infection. Microbes Infect.11:230-237.
- Janvilisri T., J. Scaria, A. Thompson, A. Nicholson, B. Limbargo, L. G. Arroyo, J. G. Songer, Y. T. Grohn, and Y. F. Chang. 2009. Microarray identification of Clostridium difficile core components and divergent regions associated with host origin. J. Bacteriol. 191:3881-3891.
- Lin Y.P., D.W. Lee, S. P. McDonough, L. K. Nicholson, Y. Sharma, and Y. F. Chang.2009. Repeated domains of leptospira immunoglobulin-like proteins interact with elastin and tropoelastin. J. Biol. Chem. 284:19380-19391.
- Lin Y.P., A. Greenwood, L. K. Nickolson, Y. Sharma, S. P.McDonough,
and Y. F. Chang. 2009. Fibronectin binds to and induces
conformational change in a disordered region of Leptospiral
immunoglobulin-like protein B. J. Biol. Chem. 284:23547-23557.
Last Update 10 August 2009
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| Department of Population Medicine & Diagnostic Sciences |
| College of Veterinary Medicine - Upper Tower Road - Cornell University - Ithaca, NY 14853-6401 |
| Phone: 607.253.4136 |
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