Lei Jin, PhD, MSc
|BSc||Fudan University, China||Biophysics|
|MSc||Fudan University, China||Human Genetics|
|Postdoctoral Fellow||National Jewish Health/University of Colorado Denver||Immunology|
Vaccines are one of the greatest achievements of biomedical science. Most vaccines are injected. There is a growing interest in developing and improving vaccines that can be inhaled. This delivers the vaccine directly to the mucosal surfaces that line the nose and lungs, which is a more effective way to produce immunity against respiratory pathogens such as pneumococcus and influenza. As these mucosal vaccines are also relatively cheap and easy to apply, they would also be suitable for use in developing countries and during emergencies. Developing safe and effective mucosal vaccine adjuvants, which help to boost targeted immune response, is key to the development of mucosal vaccines. Currently, there is no approved mucosal vaccine adjuvant in U.S.
Cyclic dinucleotides (CDNs) are promising mucosal vaccine adjuvant candidates. They elicit potent and balanced humoral and cellular immune response protecting animals from virus and bacterial infection. CDNs include cyclic di-AMP (CDA), cyclic di-GMP (CDG) and the newly discovered 2’5’-3’5’-cyclic GMP-AMP (2’3’-cGAMP). STING (stimulator of interferon genes) is the mammalian receptor for CDNs. We first showed that the mucosal adjuvant CDNs enhance antigen uptake and process in animals and directly activates dendritic cells (DC) in vivo. We further showed that STING-dependent TNFα production is critical for the mucosal adjuvant activity of CDNs in vivo.
Our goal is to i) decipher the in vivo cellular and molecular mechanism of action of CDN; ii) advance CDN as safe and efficacious mucosal vaccine adjuvants in human. The approaches we are using including knockout, knockin mice, conditional knockout, and conditional WT mice. We are also endeavoring to expand our research in human samples and cells.
Other research interests in the lab include i) Understanding the effects of common human STING variations on licensed pneumococcal vaccines Pneumovax®23 and Prevnar13® effectiveness in vivo; ii) Understanding the role of STING in host defense against pneumococcal infections in vivo.
- American Association of Immunologists
- International Cytokine and Interferon Society
- 2012 – Marie Curie Fellow – European Commission
- 2015 – The Gary and Janis Grover Young Scientist Award- Albany Medical College
- Ongoing Research Support
- NIH-5R01AI110606: Mechanisms of STING-Mediated Mucosal Vaccine Adjuvant Activity of Cyclic di-GMP – 2014 ~2019
- NIH-1R21AI125999: Impact of Human STING Variants on Pneumococcal Vaccine Effectiveness – 2016~2018
- Completed Research Support
- NIH-R56AI110606: Mechanisms of STING-Mediated Mucosal Vaccine Adjuvant Activity of Cyclic di-GMP – July 2014 ~ Nov 2014
- NIH-R21AI099346 (Subcontract): Mouse Modeling of a Human STING Gene Variant for Infectious Disease – 2012 ~ 2015
- Jin L, Waterman PM, Jonscher KR, Short CM, Reisdorph NA, Cambier JC. MPYS, a novel membrane tetraspanner, is associated with major histocompatibility complex class II and mediates transduction of apoptotic signals. Mol Cell Biol. 2008 Aug;28(16):5014-26.
- Jin L, Xu LG, Yang IV, Davidson EJ, Schwartz DA, Wurfel MM, Cambier JC. Identification and characterization of a loss-of-function human MPYS variant. Genes Immun. 2011 Jun;12(4):263-9
- Jin L, Hill KK, Filak H, Mogan J, Knowles H, Zhang B, Perraud AL, Cambier JC, Lenz LL MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP. J Immunol. 2011 Sep 1;187(5):2595-601
- Blaauboer SM, Gabrielle VD, Jin L MPYS/STING-mediated TNF-alpha, not type I IFN, is essential for the mucosal adjuvant activity of (3′-5′)-cyclic-di-guanosine-monophosphate in vivo. J Immunol. 2014 Jan 1;192(1):492-502
- Blaauboer SM, Mansouri S, Tucker HR, Wang HL, Gabrielle VD, Jin L The mucosal adjuvant cyclic di-GMP enhances antigen uptake and selectively activates pinocytosis-efficient cells in vivo. Elife. 2015 Apr 21;4.
- Complete List of Publications
- Patel, S., Blaauboer, S.M., Tucker, H.R., Mansouri, S., Ruiz-Moreno, J.S., Hamann, L., Schumann, R.R., Opitz, B., Jin, L. The Common R71H-G230A-R293Q Human TMEM173 Is a Null Allele. J Immunol. 198(2):776-787, 2017 (Highlighted In This Issue, top 10% of the articles published in the Journal).