|William Langridge, PhD|
|Professor, Biochemistry and Microbiology|
|School of Medicine|
|University Faculty Profile|
Dr. Langridge's laboratory research interests in the Center for Health Disparities and Molecular Medicine are focused on enhancement of subunit vaccine protection and therapeutic treatment for infectious and inflammatory autoimmune diseases to decrease the disparities in health care among the people in industrialized and developing nations.
(a) Our laboratory is developing multi-component mucosal subunit vaccines, composed of fusion genes encoding enterotoxin B subunit lectins genetically linked to pathogen antigens to generate adjuvanted antigen conjugates that stimulate innate and adaptive immune responses to provide increased protection against infectious disease pathogens such as Rotavirus, Norwalk virus, Anthrax, HIV-1, Enterotoxigenic E. coli, Cholera, Hepatitis B, and Rabies virus. Innovations leading to the improvement of mucosal vaccine efficacy will reduce the cost of protection against infectious diseases and will help to reduce the health-care disparity among middle and lower socio-economic groups.
(b) Using similar mucosal vaccination enhancement strategies, our laboratory is developing subunit vaccines for protection and treatment of diabetes. Enterotoxin B subunit linked pancreatic islet autoantigens stimulate immunotolerance responses and suppress diabetes onset. Development of DNA and virus-based mucosal diabetes vaccines combines recombinant plasmid DNA priming with a recombinant vaccinia virus or transgenic edible plant boost. This novel prime-boost subunit vaccination strategy holds promise for amplification of the mucosal immune response to subunit vaccines and is supported by an NIH award from NIDDK for immune suppression of inflammation based autoimmune diabetes.
(c) In collaboration with Theresa Strong's lab at the University of Alabama, DNA and recombinant vaccinia virus subunit vaccines are under development for delivery of cholera toxin B subunit -fusions with the adenomatous polyposis coli (APC) and carcinoembryonic antigen (CEA) genes to break immune tolerance to CEA and APC marker proteins synthesized in colon adenomas. Increased immunogenicity of colon tumors will increase the effectiveness and lower the cost of colon cancer therapy, which will help to reduce the health-care disparity in the African-American population which is at a significantly higher risk for colon cancer.
Dr. Langridge is a member of the faculty of the newly established Loma Linda University School of Medicine Center for Health Disparities and Molecular Medicine (CHDMM). Dr. Langridge received his doctorate in biochemistry (developmental biology) from The University of Massachusetts at Amherst under the mentorship of Dr. Frank DeToma and completed his post-doctoral studies in the molecular biology of invertebrate viruses at the Boyce Thompson Institute in New York City under the mentorship of Dr. Donald Roberts. His graduate and post-doctoral studies were supported by graduate assistantships from Amherst and Mount Holyoke Colleges and a genetics training grant from the National Institutes of Health (NIH).
Dr. Langridge's focus is on the development of research programs in the prevention and therapy of autoimmune diseases, specifically Type 1 and Type 2 diabetes. Dr. Langridge is the principal investigator of NIAID and NIDDK NIH awards focused on elucidating the mechanism of Type 1 diabetes and infectious enteric diseases that cause extensive loss of life of children in developing countries around the world.
The events surrounding 9/11/2001 have generated a prohibitive climate for obtaining bacterial and plant enterotoxin proteins from industrial sources for immunological and structural studies. Our research on the cholera toxin, ricin toxin, and shigatoxin B subunit immunomodulatory proteins over the past decade has placed us in an ideal position to supply these proteins to investigators needing them for their research.
During Dr. Langridge's professional career he has served as a panelist for the National Institutes of Health, Department of Health and Human Services, Bethesda, MD. Dr. Langridge has received research funding from the National Institutes of Health (NIDDK, NIAID), the National Science Foundation (NSF), the National Science and Engineering Research Council (NSERC) and the University of Alberta and Loma Linda University.
1. Choi NW, Estes MK, Langridge WH. (2006). Mucosal immunization with a ricin toxin B subunit-rotavirus NSP4 fusion protein stimulates a Th1 lymphocyte response. J Biotechnol. Jan 24;121(2):272-83.
2. Carter JE 3rd, Yu J, Choi NW, Hough J, Henderson D, He D, Langridge WH. (2006). Bacterial and plant enterotoxin B subunit-autoantigen fusion proteins suppress diabetes insulitis. Mol Biotechnol. Jan;32(1):1-15.
3. Choi NW, Estes MK, Langridge WH. (2005). Oral immunization with a shiga toxin B subunit: rotavirus NSP4(90) fusion protein protects mice against gastroenteritis. Vaccine. Oct 25;23(44):5168-76.
4. Denes, B., Krausova, V., Yu, J., Fodor, T., Timiryasova, T., Fodor, I. and Langridge W.H.R. (2005). Recombinant vaccinia viruses containing cholera toxin-islet autoantigen fusion genes protect NOD mice against autoimmune diabetes. Journal of Immunotherapy, 28(5) 438-448.
5. Umphress, S., Timiryasova, T.M., Arakawa, T., Hilliker, S., Fodor, I. and Langridge, W.H.R. (2003), Vaccinia virus mediated expression of human APC induces apoptosis in colon cancer cells. Transgenics, Vol 4:19-33.
6. Yu, J. and Langridge, W.H.R., (2001), A plant-based multicomponent vaccine protects mice from enteric diseases.Nature Biotechnology, June,19:548-552.
7. Langridge, W.H.R., (2000), Edible vaccines. Scientific American. Vol.283:3, 48-53.
8. Arakawa, T., Yu J., and Langridge W.H.R. (1999), Food plant delivered cholera toxin B subunit for vaccination and immunotolerization. Adv. Exp. Med. Biol, 464:161 78.
9. Arakawa, T., Chong, D.K.X. and Langridge W.H.R., Efficacy of a Food Plant-Based Oral Cholera Toxin B Subunit Vaccine (1998), Nature, Biotechnology Vol.16,292-297.
10. Arakawa, T., Chong, D.K.X., Yu, J., Hough, J., Engen, P.C., Elliott, J.F. and Langridge W.H.R., (1998), a Plant-based Cholera Toxin B Subunit-insulin Fusion Protein Protects Against Development of Autoimmune Diabetes, Nature Biotechnology, Vol.16:934-938.