Welcome to Frank Yang Lab

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The Frank Yang laboratory focuses on bacterial pathogenesis—how bacterial pathogens colonize the host, evade host immune response and cause diseases. The ultimate goals are to develop new diagnostic tools and vaccine to detect and prevent infections.

The primary focus of The Frank Yang Lab revolves around researching the pathogenesis of Lyme disease. As the leading vector-borne disease in the United States, Lyme disease poses a significant health concern. However, the understanding of how the causative agent, Borrelia burgdorferi, induces various manifestations such as Lyme arthritis, Lyme carditis, and neuroborreliosis remains limited. Presently, there is a notable absence of a human vaccine for preventing Lyme disease, and the diagnostic capabilities are suboptimal.

 

One area of the Lyme disease research is to elucidate the strategies B. burgdorferi employs that allow the pathogen to survive in the mammalian host and the tick vector. The laboratory has identified two key regulatory networks (Hk2-Rrp2, Hk1-Rrp1) and two di-nucleotide secondary messengers (c-di-GMP, c-di-AMP), that are essential either for the pathogen to infect mice or to survive in the tick vector. These pathways control many differentially expressed genes, and are potential targets for vaccine candidate or for diagnosis development.

 

 

 

 

Another area of the Lyme disease research is to study the mechanism of immune evasion by B. burgdorferi for its persistent infection. Differential expression of VlsE that undergoes antigenic variation is a key immune evasion strategy employed by B. burgdorferi. vlsE expression increases concomitantly with downregulation of the major immunodominant surface lipoprotein OspC in response to host adaptive immune response activation. The laboratory discovered a key transcription factor, YebC, that regulates vlsE expression. This finding sets the foundation to study how the pathogen senses the immune pressure to activate the VlsE antigenic variation system and provides a potential therapeutic target to combat persistent Lyme disease.

In addition to Lyme disease, the Frank Yang Lab also works on identification of factors as potential candidates for diagnosis and vaccine development against Syphilis (one of the important sexual transmitted infections caused byTreponema pallidum) and Leptospirosis (a re-emerging zoonotic disease caused by Leptospira interrogans).

 

Current Research Funding

5R01, AI083640 (Yang),                                                                     6/2023-5/2028

Regulatory Network of the Lyme Disease Pathogen

 

R01AI152235 (Yang, Sintim)                                                             6/2020-5/2025

Targeting Cyclic Dinucleotide Signaling Pathways to Interrupt the Nature Cycle of Borrelia burgdorferi

 

R21, NIH-NIAID AI169333-01A1 (Yang)                                            5/2022– 4/2024

The Role of YebC in persistent infection of the Lyme disease pathogen                          

 

Steven & Alexandra Cohen Foundation (Yang, Sintim)                    5/2020-4/2024

Development of Novel Therapeutic Compounds against Active and Persistent Borrelia burgdorferi

 

Selected Publications

1.       Alazani F, Ranghunandanan S, Priya R, Yang XF*. 2023. The RpoN-RpoS regulatory pathway plays an important role in the blood-brain barrier transmigration of the Lyme disease pathogen. Infection and Immunity. 91(11):1-12, e0022723. doi: 10.1128/iai.00227-23.

2.       Priya, R., Raghunandanan, S., Alanazi, F. and Yang XF*. 2023. Borrelia burgdorferic-di-AMP induces type I IFN response in macrophage through the activation of STING signaling pathway. The Journal of Immunology, 210, 241.207.

3.       Zhang Y, Chen T, Raghunandanan S, Xiang X, Yang J, Liu Q, Edmondson DG, Norris S, Yang XF*, Lou Y*. 2020. YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi. PLOS pathogens. 16(10), e1008953. doi: 10.1371/journal.ppat.1008953.

4.       Zhang JJ, Yang Y, Troxell B, He M, Carrasco S, Du J, Li H, Gomelsky M, Yang XF*. 2018. Dual Roles of c-di-GMP Binding Protein PlzA in the Regulation of Glycerol Uptake and Metabolism in Borrelia burgdorferi. Journal of Bacteriology. 200 (22) e00243-18; DOI: 10.1128/JB.00243-18

5.       Zhang JJ, Hu WL, Yang YY, Picardeau M, Yan J, Yang XF*. 2018. The sigma factor σ54 is required for the long-term survival of Leptospira biflexia in water. Molecular Microbiology. 109(1): 63-77. PMID: 29633391; DOI: 10.1111/mmi.13967

6.       Radolf JD, Deka RK, Anand A, Šmajs D, Norgard MV, Yang XF. 2016. Treponema pallidum, the syphilis spirochete: making a living as a stealth pathogen. Nature Review Microbiology. 14(12):744-759.

7.       Chou S, Daugherty M, Peterson S,  Biboy J, Yang Y, Jutras B, Fritz-Laylin L, Ferrin M, Harding B, Jacobs-Wagner C, Yang XF, Malik H, Vollmer W, Mougous J. 2015. Transferred interbacterial antagonism genes augment eukaryotic innate immune function. Nature. 518(7537):98-101. PMCID:PMC4713192

8.       Troxell B, Xu H, Yang XF*. 2012. Borrelia burgdorferi, a pathogen that lacks iron, encodes a Mn-dependent superoxide dismutase that is required for resistance to streptonigrin.  Journal of Biological Chemistry. 287(23):19284-93.

9.       He M, Ouyang Z, Troxell B, Xu H, Moh A, Norgard M, Piesman J, Gomelsky, M, Yang XF*. 2011. c-di-GMP is essential for the enzootic cycle of Borrelia burgdorferi.  PLoS Pathogens. 7(6): e1002133

10.   Xu H, Caimano M, Lin T, He M, Radolf J, Norris S, Gherardini F, Wolfe A, Yang XF*.  2010. Role of acetyl-phosphate in activation of the Rrp2-RpoN-RpoS pathway in Borrelia burgdorferi.  PLoS Pathogens. 6(9): e1001104. doi:10.1371/journal.ppat.1001104

 

Click here for a full list of publications in PubMed

 

Research Team

Sajith Raghunandanan, Ph.D., Postdoc Fellow

Raj Priya, Ph.D., Postdoc Fellow

Gaofeng Lin, Ph.D., Research Scientist

Fuad Alazani, Ph.D. Candidate

Elise Warren, BS, Research Technician