Jian-Dong Li, M.D., Ph.D.
Inflammation and Immunity
Georgia State University
J. D. Li studies the biological processes of inflammation – how and why it begins, and how it can be alleviated in everything from an annoying stuffy nose to chronic conditions such as rheumatoid arthritis and potentially fatal pulmonary obstruction disorder.
In 2013, Li published findings that showed inflammation could be relieved by inhibiting the molecule PDE4B (phosphodiesterase 4B). When PDE4B levels decreased, there was a corresponding increase in CYLD – an enzyme that tells the body’s cells to reduce inflammation. This approach was a marked change from previous studies, which attempted to reduce the flow of signals that spur inflammation, yielding undesirable side effects.
With Li’s discovery comes the promise of new anti-inflammatory drugs, potentially to be manufactured by ROCK Pharmaceuticals, of which Li is a cofounder. New drugs would be welcome alternatives to steroids, which can have serious side effects. Among the promising drug candidates the company would like to produce and market is Vinpocetine, used in Europe and Asia for decades as a treatment for memory loss, now being shown effective as an anti-inflammatory.
- Inducible negative feedback regulation of inflammation. Building on the recent finding that CYLD, a deubiquitinase, acts as an inducible negative feedback regulator for inflammation. New insights into the tight regulation of inflammation may lead to the identification of novel therapeutic targets. Future studies will focus on identifying the novel molecular targets of CYLD and the underlying signaling mechanisms involved in inflammatory and infectious diseases, as well as investigating the mechanisms by which CYLD is induced.
- Regulation of host survival in S. pneumoniae and influenza infections. Streptococcus pneumoniae (S.p.) is a major cause of morbidity and mortality worldwide. It is a major cause of community-acquired pneumonia (CAP) and also considered as a significant cause of a secondary infection associated with influenza virus infections. It is unclear why the mortality rate remains very high at an early stage. CYLD plays a critical role in potentiating the S. pneumoniae-induced lethality. Research focuses on investigating the molecular targets and the underlying signaling mechanisms by which CYLD regulates S. pneumoniae-induced lethality.
- Regulation of mucus overproduction in bacterial infections. Mucus overproduction is a hallmark of upper respiratory tract infections. How mucus is up-regulated remains largely unknown. Li’s lab has identified several positive signaling pathways involved in mucus overproduction, and is now working to determine the negative regulators involved in preventing overactive mucus overproduction and further exploring their translational potential.
- Development of novel therapeutic agents for inflammatory and infectious diseases. Developing Vinpocetine into an anti-inflammatory therapeutic agent and developing novel therapeutic agents for inhibiting mucus overproduction and reducing lethality.
Li’s multidisciplinary research comprises molecular genetics, cell biology, biochemistry, molecular biology, immunology, chemical biology, pharmacology, functional genomics and proteomics, and transgenic animals, so he was attracted to the collaborative environment at Georgia State. His instincts were right: One of his major findings was a joint effort with fellow Eminent Scholar Binghe Wang.