Events

Pharmaceutical Sciences Seminar Series

(Drug ACTION Specific Seminar)

• Nan Gao, PhD
• Rutgers University

Non-canonical Paneth cell functions regulate intestinal inflammatory response

Paneth cells are the primary source of C-type lysozyme, a β-1,4-N-acetylmuramoylhydrolase that enzymatically processes bacterial cell walls. Aberrant lysozyme production are hallmarks of inflammatory bowel disease (IBD) pathology. I will show experiments that demonstrate the impact of lack or ectopic lysozyme production on colonic inflammation. I will also show data about how Lyz1-deficiency modulates the gut bacterial composition and intestinal immune responses to bacterial molecular patterns. I will present biochemical and immunology evidence to suggest that Paneth cell lysozyme balances intestinal anti- and pro-inflammatory responses.

In addition, I will shed light on our recent finding that a direct engagement of intestinal lysozyme with enteric pathogens such as Salmonella promotes the release of bacterial virulence factors that are barrier-impairing and pro-inflammatory.

In the end I’ll discuss our ongoing work investigating the Paneth cell subsets that may be important for host responses to infection and inflammation.

Hosted by Ting Fu

2024 WARF Therapeutics Distinguished Lecture in Drug Discovery

• Jeffrey Aube, PhD
• University of North Carolina

New Approaches to Tuberculosis Therapeutics

Tuberculosis (TB) continues to be a major worldwide health problem, despite the existence of numerous drugs for its treatment. This is in part due to the long therapeutics times required to administer cocktails of front-line therapeutics and in part due to the emergence of even more challenging long-term strains. For these reasons, new therapeutic agents for the treatment of TB continue to be sought. In collaborative work with the laboratory of Carl Nathan (Weill–Cornell Medicine) and others, we have sought to find new chemotypes as potential anti-TB agents and to identify new biochemical targets for drug treatment. In this talk, I will describe our efforts in this area, beginning with early approaches to explore beta-lactam antibiotics as possible TB agents. More recent efforts have been focused on finding inhibitors of phosphopantetheinyl transferase (PptT). PptT carries out central biochemistry that is essential for mycobacterial survival; for this reason, it has been a long sought-target for antibacterial agent development. This story begins with our team’s discovery of the first effective small-molecule inhibitors of PptT, efforts to use bioisostere design to create a new series, and more recent chemotypes of PptT.

Hosted by Jennifer Golden