Jae Jung’s Laboratory and Research Interests:
My laboratory studies Infection, Inflammation and Immunity (3I) and currently consists of Postdoctoral Fellows, Ph.D students, Master’s students, research assistants and one administrator.
My laboratory (http://uscmmi.com/jaejunglab/) studies Virus-induced Cancer, Emerging Pathogen and Inflammation/Immunity.
1. Virus-Induced Cancer
Gamma-2 herpesviruses (KSHV) include Kaposi’s sarcoma associated herpesvirus (KSHV) and murine herpesvirus 68 (MHV68). KSHV is an etiologic agent of Kaposi’s sarcoma that is the most common tumor in patients with AIDS and MHV68, the murine counterpart of KSHV, 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, epigenetics/genomics/single cell transcriptome, persistence, pathogenesis, and vaccine development.
Hepatitis B virus (HBV):
HBV infection is the most common chronic viral infection in the world and there is currently no cure. The virus itself is not cytopathic, but inflammation driven by chronic HBV infection significantly elevates the risk for developing liver cirrhosis and carcinoma. The goal of our study is to establish a 3D culture model (mini-liver organoid) for productive HBV infection as a platform to dissect the roles of host factors in HBV replication and pathogenesis.
2. Emerging viruses
Emerging virus includes misquote-borne virus, tick-borne virus and respiratory zoonotic coronavirus.
Dengue virus (DENV) and Zika virus (ZIKV):
Dengue virus (DENV) is a single positive-stranded RNA virus of the Flavivirus family and causes a spectrum of diseases. Zika virus (ZIKV) is closely related to DENV and transmitted by Aedes mosquitoes. ZIKV infection is a key risk factor for microcephaly and neurological diseases.
Severe Fever with Thrombocytopenia virus (SFTSV) and Heartland virus (HRTV):
Severe Fever with Thrombocytopenia virus (SFTSV) is an emerging tick-borne infectious agent that has a fatality rate of 15-30% by causing multiple organ failure, thrombocytopenia, and leukopenia. Heartland virus (HRTV) has been identified in the Midwestern and southern United States and causes symptom and fatality similar to those of SFTSV. SFTSV and HRTV are a three-segmented negative-stranded RNA virus of the Bunyavirus family.
Coronaviruses (CoV) are a large family of viruses that cause respiratory and intestinal infections in animals and humans. The recent massive outbreak of newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spread worldwide, leading to a serious public health concern and global health emergency.
Understanding how DENV, ZIKV, SFTSV, HRTV and SARS-CoV-2 evade host immune system and cause diseases in in vitro culture and animal models, and how therapeutics and vaccine can be developed against these emerging viruses is the main topics of interest.
3. Inflammation and Immunity
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 neuroinflammation:
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.
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.
Nonalcoholic fatty liver disease (NAFLD):
NAFLD is a condition in which excess fat is stored in liver. Non-alcoholic steatohepatitis (NASH) is a form of NAFLD that has inflammation and cell damage in addition to fat in liver. As inflammation and liver cell damage can cause fibrosis, or scarring, of the liver, NASH may lead to cirrhosis or liver cancer. We have developed a novel NAFLD mouse model. Using this mouse model, we study the development of obesity, fatty liver disease and liver cancer.
4. Viral vector, oncolytic virus and vaccine stabilization
Instability of viral vector, oncolytic virus and vaccine often emerges as a key challenge during clinical development as well as commercial distribution.
To yield stable, efficacious viral vector, oncolytic virus and vaccine for human use, successful formulation strategies must address a combination of interrelated topics including stabilization of biological activity and antigens, selection of appropriate delivery and adjuvants, and development of stability-indicating analytical methods.
Our goal is to develop thermostable viral vector and oncolytic virus for clinical usages and thermostable vaccine for distribution in developing countries without the need of a cold-chain transport.