Dr. Langridge's research interests in the Center for Health Disparities and Molecular Medicine are focused on development of protein adjuvants to enhance subunit vaccine protection and therapeutic treatment for infectious and inflammatory autoimmune diseases with the goal of decreasing present disparities in health care.
(a) Our laboratory is developing multi-component mucosal subunit vaccines, composed of genes encoding bacterial enterotoxin B subunit adjuvant molecules linked to pathogen antigens to provide immunoenhanced antigen conjugates that stimulate innate and adaptive immune responses that generate enhanced protection against viral and bacterial pathogens such as Rotavirus, Enterotoxigenic E. coli, Cholera, Norwalk virus, Anthrax, HIV-1, Hepatitis B, and Rabies virus. Innovations leading to improvements in subunit vaccine efficacy will reduce the cost of protection against infectious diseases and will help reduce health-care disparities among middle and lower socio-economic groups.
(b) Dr. Langridge’s laboratory is exploring adjuvant stimulated subunit vaccine protection and therapy for suppression of diabetes inflammation. Bacterial enterotoxin B subunit linked pancreatic islet autoantigen fusion proteins activate mechanisms of immunological tolerance to suppress the onset of diabetes. DNA and virus-based diabetes vaccine development combines recombinant plasmid DNA priming with an attenuated vaccinia virus or transgenic edible plant boost. This heterologous prime-boost subunit vaccination strategy promises amplification of mucosal immune responses 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 Loma Linda University School of Medicine, Center for Health Disparities and Molecular Medicine (CHDMM). Dr. Langridge received his doctorate in the biochemistry of animal development from the University of Massachusetts at Amherst, under the mentorship of Dr. Frank DeToma and completed his post-doctoral studies on 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 awarded by the National Institutes of Health (NIH).
Dr. Langridge's main research focus is on mechanisms of chronic inflammation underlying the onset and development of autoimmune diseases, specifically Type 1 and Type 2 diabetes. Dr. Langridge is the principal investigator on NIAID and NIDDK NIH awards focused on the development of preventive and therapeutic strategies for Type 1 diabetes and infectious enteric bacterial and viral diseases responsible for extensive loss of life of children in developing countries around the world.
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 of Canada, (NSERC) and the University of Alberta, Alberta, Canada and Loma Linda University in Southern California.
1. Oludare Odumosu, Mavely Baez, Jessica Jutzy, Kimberly Payne, Nathan Wall, William Langridge (2010). Suppression of Dendritic Cell Activation by Diabetes Autoantigens Linked to the Cholera Toxin B Subunit. (Accepted, Immunobiology, Elsevier, August, 2010).
2. William Langridge, Béla Dénes and István Fodor (2010). Cholera toxin B subunit enhancement of vaccines for infectious and autoimmune diseases Current Opinions in Investigational Drugs. Thomson Reuters Press, 77 Hatton Garden, London, EC1N 8JS, UK 2010 11(8):919-928.
3. Denes, B., Fodor, I. and Langridge W.H.R., (2010).Autoantigens plus Interleukin-10 Suppress Diabetes Autoimmunity, Diabetes Technology and Therapeutics 12:8,.
4. Carter, J.E., Odumosu, O. and Langridge, W.H.R. (2010). Expression of a Ricin Toxin B Subunit :Insulin Fusion Protein in Edible Plant Tissues. Molecular Biotechnology, Feb;44(2):90-100.
5. Eun-Ah Shin, Ph.D.; Yong Keun Park, Ph.D.; Kang Oh Lee, Ph.D.; William Henry Langridge, Ph.D.Jin-Yong Lee, Ph.D. (2009). Synthesis and assembly of Porphyromonas gingivalis fimbrial protein in potato tissues. Molecular Biotechnology 43: 2, 138.
6. Eun-Ah Shin, Ph.D.; Yong Keun Park, Ph.D.; Kang Oh Lee, Ph.D.; William Henry Langridge, Ph.D.Jin-Yong Lee, Ph.D. (2009). Synthesis and assembly of Porphyromonas gingivalis fimbrial protein in potato tissues. Molecular Biotechnology 43: 2, 138.
7. Khan S, JR Aspe, MJ Asumen, F Almaguel, O Odumosu, S Acevedo-Martinez, MN De Leon, WHR Langridge and NR Wall. (2009). Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential. British Journal of Cancer 7;100(7):1073-86.
8. Daniell H, Ruiz G, Denes B, Sandberg L and Langridge W (2009). Optimization of codon composition and regulatory elements for expression of the human insulin like growth factor-1 in transgenic tobacco chloroplasts and evaluation of structure and function. BMC Biotechnology 9:33, 1186.
9. Tae-Geum Kim , Nguyen-Xuan Huy , Mi-Young Kim , Dong-Keun Jeong, Yong-Suk Jang, Moon-Sik Yang , William H. R. Langridge and Jin-Yong Lee (2009), Expression and Immunogenicity of Cholera Toxin B Subunit-Porphyromonas gingivalis Fimbrial Antigen Fusion Proteins in E. coli, Molecular Biotechnology. Feb;41(2):157-64.
10. Dénes Béla , Yu Jie , Fodor Nadja , Takátsy Zsuzsanna , Fodor István , Langridge William H. R. (2006), Suppression of hyperglycemia in NOD mice after inoculation with recombinant vaccinia viruses. Molecular Biotechnology, November, Volume 34, Issue 3(Original Research) pp. 317-328.
11. Shin EA, Lee JY, Kim TG, Park YK, Langridge WH. (2006). Synthesis and assembly of an adjuvanted Porphyromonas gingivalis fimbrial antigen fusion protein in plants.
Protein Expression and Purification. May;47(1):99-109.
12. Choi NW, Estes MK, Langridge WH. (2006). Ricin toxin B subunit enhancement of rotavirus NSP4 immunogenicity in mice. Viral Immunology. Spring;19 (1):54-63.
13. Langridge W.H.R. (2006). Edible vaccines, Scientific American Reports, Dec.Vol 1; 46-53.
14. 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. Molecular Biotechnology. Jan;32(1):1-15.
15. 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.
16. Kim TG, Yu J, Hough J, Henderson D, Langridge WH. (2005). An HIV-1 tat-autoantigen fusion protein suppresses insulitis in NOD mice. Molecular Biotechnology. Jul;30(3):221-9.
17. Denes, B., Krausova, V., Yu, J., Fodor, T., Timiryasova, T., Fodor, I. and Langridge W.H.R. (2005). Protection of NOD mice from type 1 diabetes after oral inoculation with vaccinia viruses expressing adjuvanted islet autoantigens. Journal of Immunotherapy, 28(5) 438-448.