Approximately 15% of cancers diagnosed were attributed to carcinogenic viral infections. Upon viral infections, the host innate immune system acts as the first line of host defense to prevent viral invasion or replication, while viruses also strive for survival by repressing innate immune signaling. By gaining a further understanding of how innate immunity is regulated by tumor viruses, our lab aims to dissect innate immune responses and viral tumor development for the sake of identifying potential targets and strategies for viral cancer treatment.
Kaposi’s sarcoma associate herpesvirus (KSHV) is the etiological agent for several malignancies in the human population including Kaposi’s sarcoma (KS), multicentric Castleman’s disease (MCD), and primary effusion lymphoma (PEL). Although innate immunity is critical for comprehensive antiviral responses to clear viral infections and limit viral tumor proliferation, exactly how the innateimmune system senses tumor viruses, such as KSHV, is not well understood at the molecular level. By investigating the interplay between the innate immune system, KSHV, and KSHV-associated cancers will help us develop better therapies to treat not only KSHV related malignancies, but also broaden our knowledge to other viral cancers.
Previously, we have found that the DNA sensing cGAS-STING pathway is responsible for triggering innate immune responses upon KSHV primary infection and lytic replication. However, the fact that KSHV is capable of establishing lifelong infection in the presence of cGAS-STING signaling suggests that KSHV encodes viral regulators to modulate the cGAS-STING pathway to facilitate its viral transmission and its lifelong persistence in the human population. These potential viral regulators were successfully identified by our screening system, but their roles in KSHV infection, as well as KSHV cancer development, are still subjected to further investigation.
Therefore, our lab immediate goals will build upon these findings to extend our knowledge of how these viral proteins regulate the cGAS-STING pathway and how to develop potential KSHV cancer therapy by targeting these viral proteins. Specifically, we are focusing on:
1) Explore detailed mechanisms of cGAS-STING signaling regulation by KSHV viral proteins
2) Explore the role of KSHV viral proteins on KSHV pathogenesis in vitro and in vivo
3) Screen for novel cGAS-STING pathway agonists, and test their efficacy using PEL based xenograft mouse model
Besides, we are also actively exploring other signaling pathways that are involved in KSHV infection and KSHV cancer progression. Particularly, we aim to identify viral regulators
that are responsible for modulating some of these pathways, and further study their mechanism and roles in KSHV cancer development. Our long-term goals are to better understand
KSHV cancers and developing potential KSHV cancer treatment or vaccines.
Alone we can do so little; together we can do so much. We are always grateful for any suggestions and collaborative opportunities.
Reach me at: firstname.lastname@example.org and phone 352-273-7513.
Postdoctoral Fellow: University of North Carolina at Chapel Hill
Ph.D. Cancer Biology University of Miami
M.S. Microbiology Nankai University, China
B.E. Biochemical Engineering Tianjin University of Science and Technology, China
Awards and Professional Services:
2018 Pathway to Independence Awards (K99/R00), National Cancer Institute
2017 Postdoctoral Award for Research Excellence, University of North Carolina at Chapel Hill
2016 Best of 2016 Reviews and Perspectives, Cell host & microbe
2015 Joseph S. Pagano Award, University of North Carolina at Chapel Hill
- McNamara R, Chugh P, Bailey A, Costantini L, Ma Z, Bigi R, et al. Extracellular vesicles from Kaposi Sarcoma-associated herpesvirus lymphoma induce long-term endothelial cell reprogramming. PLOS Pathogens. 2019 Feb
- Ma Z, Ni G, Damania B. Innate Sensing of DNA Virus Genomes. Annual Review of Virology 2018 Sep
- Ni G, Ma Z, Damania B. cGAS and STING: At the intersection of DNA and RNA virus-sensing networks. PLOS Pathogens. 2018 Aug
- Ma Z, Hopcraft SE, Yang F, Petrucelli A, Guo H, Ting JP, Dittmer DP, Damania B. NLRX1 negatively modulates type I IFN to facilitate KSHV reactivation from latency. PLOS Pathogens. 2017 May
- Ma Z, Damania B. Editorial: NLRP3: immune activator or modulator? J Leukoc Biol. 2016 May
- Ma Z, Damania B. The cGAS-STING Defense Pathway and Its Counteraction by Viruses. Cell Host & Microbe. 2016 Feb (Best reviews and aspects, 2016)
- Ma Z, Jacobs SR, West JA, Stopford C, Zhang Z, Davis Z, Barber GN, Glaunsinger BA, Dittmer DP, Damania B. Modulation of the cGAS-STING DNA sensing pathway by gammaherpesviruses. Proc Natl Acad Sci U S A. 2015 Jul 21
- Ma Z, Moore R, Xu M, Barber GN. DDX24 Negatively Regulates Cytosolic RNA-mediated Innate Immune Signaling. PLOS Pathogens 2013 Oct 9(10):e1003721.
- Ishikawa H, Ma Z, Barber GN. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature. 2009 Oct 8;461(7265):788-92
- Ma Z, Hao P, Yao X, Liu C, Tan J, Liu L, Yang R, Geng Y, Chen Q, Qiao W. Establishment of an indicator cell line to quantify bovine foamy virus infection. J Basic Microbiol. 2008 Aug;48(4):278-83.
- Ma Z, Qiao WT, Xuan CH, Xie JH, Chen QM, Geng YQ. Detection and analysis of bovine foamy virus infection by an indicator cell line. Acta Pharmacol Sin. 2007 Jul;28(7):994-1000.