Jae U. Jung

PIBBS MENTOR
Distinguished Professor
Fletcher Jones Foundation Professor
Hastings Foundation Professor
Chair of Department of Molecular Microbiology and Immunology
Director of USC Institute of Emerging Pathogens

Affiliated with Molecular Microbiology and Immunology, Keck School of Medicine and School of Pharmacy

Research Topics

  • cancer cell biology
  • cell cycle
  • growth & proliferation
  • cell death
  • membranes & transport
  • signal transduction
  • cancer biology
  • gene regulation & transcription
  • microbial & invertebrate genetics
  • immunology
  • virology

Research Images

Research Overview

My laboratory is conducting four different areas of research:


1.  Host-Pathogen Standoff


Hosts: The first step to mounting a protective immune response is the recognition of pathogens by cell surface receptors, called pattern recognition receptors (PRRs), including C-type lectin receptors, Toll-like receptors, NOD-like receptors, and cytoplasmic RIG-I-like helicases. After recognizing specific pathogen-associated molecular patterns, PRRs activate intracellular signaling pathways and trigger effector immune mechanisms as well as the initiation of adaptive immunity, ultimately resulting in the elimination of the pathogen from the infected host. Our focus in this section is to understand the PRR-mediated anti-microbial responses with a specific focus on the ubiquitination-dependent regulations of PRR responses.

Herpesvirus: To avoid the host innate and adaptive immune responses, herpesviruses have evolved elaborate mechanisms to target and modulate differing aspects of the host’s immune system. Understanding these herpesvirus-mediated immune evasion tactics is the primary goal of this avenue.

Interferon (IFN) and Influenza virus: Upon viral infection, the major defense mounted by the host immune system is activation of the IFN-mediated anti-viral innate immune pathway. In order to complete their life cycle, viruses must modulate host IFN-mediated immune response. We study how the host recognizes viral infection with a specific focus on the RIG-I, TRIMs, IFITMs, and IRFs, and how influenza virus escapes host IFN-mediated anti-viral response with a specific focus on the Influenza virus NS1 gene.

Human immunodeficiency virus: Since viruses are most vulnerable at the early stage of their life cycles, this stage should therefore offer the best opportunity for therapeutic interventions. Specifically, antiviral “host restriction” factors interfere with different stages of the HIV early life cycle to prevent persistent infection, which is a crux of this research topic. Among many host restriction factors, IFITM, LUBAC, and SAMHD1 are being studied.

Mycobacterium tuberculosis and phagocytosis: Mycobacterium tuberculosis (Mtb) is a major intracellular pathogen of humans, with 2–3 million deaths annually from tuberculosis, and an increasing number of multidrug-resistant TB cases. The research interest of this section lies in elucidating the crosstalk between phagocytosis and autophagy to build up the effective intracellular innate immune milieu against Mtb infection and Mtb-mediated evasion of this process.

2. Virus-Induced Malignancy and Epigenetic Regulation


This section is focused on understanding the molecular mechanisms of cancers induced by the gamma-2 herpesviruses, investigating the epigenetic regulation of viral gene expression, and developing animal models for human diseases. The gamma 2 herpesviruses include murine herpesvirus 68 (MHV68), primate herpesvirus saimiri (HVS), and human Kaposi’s sarcoma associated herpesvirus (KSHV). KSHV is associated with Kaposi’s sarcoma, which is a multifocal vascular tumor of mixed cellular composition and is the most common tumor in patients with AIDS. Infection of New World primates with HVS results in rapidly progressing malignant T cell lymphomas. Finally, MHV68 provides a small animal model to study viral persistent infection. Genomic, biochemical and immunological analyses of individual viral genes in cell culture and experimental infection of mouse and primate with recombinant herpesviruses are used to investigate viral epigenetic regulation, gene expression, persistence, pathogenesis, and vaccine development.

3. Programmed Cell Death


Upon viral infection, infected cells can become the target of host immune responses or can go through a programmed cell death (PCD). Apoptosis (“to kill itself”) has been a primary PCD mechanism to respond to viral infection. Autophagy ("to eat itself") is an emerging PCD pathway that is a highly regulated homeostatic process where worn-out proteins, malfunctioning organelles, and invading pathogens are swept up and degraded by tiny “vacuum cleaners, called autophagosomes.” Thus, apoptosis and autophagy are important innate safeguard mechanisms for protecting the organism against unwanted guests like pathogens to keep it healthy. Specifically, autophagy combats and defends infected cells by enhancing the degradation of intracellular pathogens. On the other hand, to avoid host’s autophagy-mediated immune responses, herpesviruses have evolved elaborate mechanisms to block differing aspects of autophagy pathway for their persistent infection. Thus, understanding herpesvirus-mediated apoptosis and autophagy evasion tricks is the primary goal of this section.

4. Therapeutic Strategy Development


Although hundreds of targets can be identified for any given pathology, it is crucial to identify a bona fide target responsible for the disease. Therefore, small-molecules or peptides are needed as probes to perturb a unique interaction and to confirm the usefulness of a target for therapeutics development. In conjunction with three sections described above, a major emphasis of this section is the discovery of novel targets and their therapeutic strategies. Current areas of target discovery and small molecule development are inflammation and acute lymphoblastic leukemia (ALL).