The TG2/LRP1 Pathway: A Remarkable Mechanism for Antigen Presentation and More
- Prof. Chaitan Khosla, Stanford University
- Sponsored by Stanford Department of Chemistry
- 3:00-4:00 pm, In-person, Stanford University, Sapp Center Auditorium (STLC 111), 376 Lomita Drive, Learn more
In our search for an explanation to the spectacular efficiency of gluten antigen presentation to the T cells that cause celiac disease, we discovered an unexpected phenomenon. With help from an endocytic receptor, a post-translational protein modifying enzyme partitions its catalytic cycle by binding to its substrate on one side of the cell membrane and releasing its product on the other. Dubbed the TG2/LRP1 pathway, my lecture will focus on the chemical mechanism of this phenomenon, its role in the pathobiology of celiac disease, and the exploitation of these insights to advance a novel experimental medicine for celiac disease therapy into clinical trials. I will conclude by describing corollary efforts in collaboration with Bianxiao Cui’s laboratory that leverage our insights into the TG2/LRP1 pathway to prototype a different experimental medicine for the treatment of deadly fibrotic diseases.
About the Speaker
Chaitan Khosla is a professor in the departments of Chemistry and Chemical Engineering at Stanford University. His research interests lie at the chemistry-biology interface. Chaitan received his PhD in 1990 at Caltech. After completing postdoctoral studies at the John Innes Centre in the UK, he joined Stanford University in 1992. Over the past 30+ years he has mentored ~150 doctoral and postdoctoral trainees, a vast majority of whom have gone on to successful careers in academia, government or the biopharma industry across the globe. The Khosla lab’s current research interests are diverse and collaborative; they range from understanding the mechanistic and evolutionary logic of polyketide biosynthesis on enzymatic assembly-lines to fundamental and translational investigations into the pathobiology of disorders with high morbidity such as celiac disease, Alzheimer’s disease and organ fibrosis. Chaitan served as the founding director of Stanford’s ChEM-H Institute from 2012 to 2020 and presently serves as the founding director of its Innovative Medicines Accelerator. He is an elected member of the American Academy for Arts and Science, the U.S. National Academy of Engineering, and the U.S. National Academy of Sciences. Recent honors include the 2026 Abeles and Jencks Award from the American Chemical Society.