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Targeting E3 Ubiquitin Ligases as Potential Therapeutic approaches for Autoimmune/Inflammatory/Infectious Diseases

July 11, 2018

Dr. Jian Zhang

Regulation of innate immune system sensing of C. albicans infection (R01 AI123253)
Dr. Jian Zhang, received a R01 grant from the National Institute of Allergy and Infectious Diseases to study how Cbl-b controls invasive fungal infection. Fungal infections claim an estimated 1.5 million lives every year and constitute a severe health threat, especially to people with an impaired immune status. Despite the availability of several anti-fungal drugs, invasive candidiasis still has a high mortality rate ranging from 45% to 75%. High morbidity and mortality are primarily due to lack of early and accurate diagnostic tools, limited anti-fungal drugs and fungal drug resistance. It is imperative to further understand host-pathogen interactions and the mechanisms of immune resistance to fungal spread, and to develop alternative immune-based strategies to combat candidemia. Dr. Zhang’s group identified how an E3 ubiquitin ligase called Cbl-b as a potential target in the host in fungal diseases. His study, "Regulation of innate immune system sensing of C. albicans infection,” explores how Cbl-b controls fungal recognition. His ultimate goal is to develop a host-derived immune therapy to invasive fungal infection. 

Nedd4 in T helper cell development and autoimmunity (R01 AI090901)
The National Institute of Allergy and Infectious Diseases has awarded Dr. Jian Zhang, a R01 grant. The study, “Nedd4 in T helper cell development and autoimmunity,” will investigate ways to mediate and treat autoimmune diseases. Nedd4 is required for the development of T helper (Th) 17. This molecule, if it is aberrantly activated or expressed, mediates certain autoimmune diseases such as multiple sclerosis. The discovery of Nedd4 in Th17 cell development suggests that Th17 responses can be regulated. As a therapeutic target, the molecules Nedd4 could eventually treat autoimmune diseases mediated by pathogenic Th17 cells.

Role of protein ubiquitination in sepsis (R01 AI121196)
Sepsis with its complications is a major challenge in contemporary medicine. Approximately 250,000 cases of sepsis lead to fatalities in the USA annually at huge costs for the healthcare system. Depending on the standards of medical care, the worldwide mortality rates in septic humans range from 30% to 70% with an aggregate mortality rate of ~50%. The disease process is also not fully understood, with treatment still proving highly challenging. Dr. Jian Zhang has been awarded a R01 grant entitled “Role of protein ubiquitination in sepsis” from The National Institute of Allergy and Infectious Diseases. This project will investigate how the enzyme Cbl-b modifies the function of the microbial sensor NLRP3. Understanding the role of Cbl-b in regulating the NLRP3 inflammasome-mediated signaling pathway will provide novel insights and therapeutic strategies to combat sepsis.