Jae Jung’s Laboratory and Research Interests
My laboratory studies Infection, Inflammation and Immunity (3I) and currently consists of twelve Postdoctoral Fellows, seven Ph.D students, three Master’s students, three research assistants, one visiting scientist and one administrator.
1. Virus-Induced Cancer
Gamma-2 herpesviruses include Kaposi’s Sarcoma-associated Herpesvirus (KSHV), Herpesvirus Saimiri (HVS), and Murine Herpesvirus 68 (MHV68). KSHV is an etiologic agent of Kaposi’s sarcoma that is the most common tumor in patients with AIDS. Infection of New World primates with HVS results in malignant T cell lymphomas. Finally, MHV68, the murine counterpart of KSHV and HVS, can be used in a small animal model to study viral persistent infection. Using viral genetics and primate/mouse models, we investigate viral gene expression, epigenetic/genomic regulation, persistence, pathogenesis, and vaccine development.
Head and neck squamous cell carcinoma (HNSCC) constitutes 90% of all oral tumors and is the sixth most common malignancy. Human papilloma virus (HPV) infections are being linked to oropharyngeal cancers. The significance of this work is to identify novel biomarkers associated with HPV infections in HNSCC to serve as a diagnostic tool of oropharyngeal cancers and to discover novel anti-tumor therapies to treat HNSCC.
2. Emerging Viruses
Flavivirus [Dengue virus (DENV) and Zika virus (ZIKV)] and Bunyavirus [Severe Fever with Thrombocytopenia virus (SFTSV) and Heartland virus (HRTV)]: DENV is a single positive-stranded RNA virus of the Flavivirus family and causes a spectrum of diseases.ZIKVis closely related to DENV and transmitted by Aedes mosquitoes. ZIKV infection is a key risk factor for microcephaly and neurological diseases. SFTSV is an emerging infectious agent that was discovered in China in 2010 and has a fatality rate of 15-30% by causing multiple organ failure, thrombocytopenia, and leukopenia. HRTV has been identified in the Midwestern and southern United States and causes symptom and fatality similar to those of other tickborne infections. SFTSV and HRTV are a three-segmented negative-stranded RNA virus of the Bunyavirus family. Understanding how DENV, ZIKV, SFTSV and HRTV evade host immune system and cause diseases and how therapeutics and vaccine can be developed against these emerging viruses is the main topics of interest.
3. Inflammation and Immunity
Host-Pathogen Standoff: The first step to mounting a protective immune response is the recognition of pathogens by pattern recognition receptors (PRRs). After recognizing specific pathogen-associated molecular patterns, PRRs activate intracellular signaling pathways to induce anti-viral immunity. To avoid host immune responses, viruses have evolved elaborate mechanisms to target and modulate various aspects of the host’s immune system. Our study is focused on understanding anti-microbial responses of intracellular PRRs including RIG-I/MDA5, cGAS, TRIMs, IFITMs, IRFs, and NLRP1/3/12 and discovering various immune evasion tactics of cancer-causing viruses and emerging viruses.
Programmed Cell Death: Upon viral infection, infected cells can go through a programmed cell death (PCD). Apoptosis has been a primary PCD mechanism for the body to respond to viral infection by sacrificing infected cells. Autophagy is an innate immune pathway wherein invading pathogens are swept up and degraded by tiny “vacuum cleaners”. Pyroptosis and necroptosis are an inflammatory form of cell death characterized by massive leakage of cytosolic contents to magnify inflammatory response. These PCDs are important innate safeguard to induce inflammation and protect the organism against harmful viruses or tumor cells. Viruses, in turn, have evolved elaborate mechanisms to subvert these PCD processes. We study how the host initiates PCD and inflammatory responses upon viral infection and how the virus escapes host intracellular PCD-mediated innate immune controls to establish persistence and pathogenesis.
Traumatic brain injury (TBI) and neuro-inflammation: Tripartite motif 9 (TRIM9) E3 ligase is a brain-specific innateimmune effector to develop balanced host immune responses against brain injury and viral infection. Specifically, TRIM9 KO mice develops serious brain injury and encephalitis upon traumatic stress, stroke or West Nile virus (WNV) infection. Using mouse TBI models, we study blood brain barrier permeability, neuronal and astrocyte proliferation and death, NF-kB-mediated brain inflammation, and WNV infection-induced encephalitis.
Lung inflammation: Mast cell-expressed membrane protein 1 (MCEMP1) highly expresses on lung-resident mast cells, macrophages and neutrophils in several inflammatory conditions such as Chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and smoking. As MCEMP1 plays a critical role in the activation of mast cells and macrophages for lung inflammation, our goal is to develop MCEMP1 as a therapeutic target to treat chronic pulmonary inflammation including COPD and IPF.
4. Vaccine Stabilization
Instability of vaccines often emerges as a key challenge during clinical development as well as commercial distribution. To yield stable, efficacious vaccine dosage forms for human use, successful formulation strategies must address a combination of interrelated topic including stabilization of antigens, selection of appropriate adjuvants, and development of stability-indicating analytical methods. Our goal is to develop thermostable vaccines for distribution in developing countries without the need of a cold-chain transport. For instance, we successfully designed the inactivated polio vaccine (IPV) in the dry state with maintenance of the vaccine potency with ~96% recovery efficiency after the incubation at ambient temperature for 4 weeks and 100% vaccine capacity in animal models. We continuously expand this stabilization program to other vaccines, such as measles virus, that require cold-chain production and transport.