Development of a targeted protein degradation platform to accelerate translational research at UW–Madison

This project positions the UW–Madison to be at the forefront of a new area of drug discovery and development by establishing a targeted protein degradation platform in the Medicinal Chemistry Center to modulate activity of target proteins for both basic biological research and translational applications. Numerous human diseases are caused by the dysfunction of specific proteins. Having small molecule compounds that can remove a specific disease-causing protein would be of significant therapeutic value such as in treatment of cancers or infectious diseases.

CRISPR and RNAi have been used extensively in biological studies for knocking out or knocking down a specific gene. Compared to these genetic tools, small molecules can act quickly, reversibly and are easily administered. However, until very recently, there has not been a general strategy to develop small molecules that can remove any specific protein.

Targeted protein degradation using cell permeable bifunctional small molecules has emerged as a revolutionary technology for drug discovery. It has become an exciting therapeutic option to confront diseases involving overexpressed, mutated or viral disease-causing proteins by engaging the body’s natural protein disposal system.

PRINCIPAL INVESTIGATOR
Weiping Tang, professor of pharmaceutical sciences and director of the UW Medicinal Chemistry Center

CO-PRINCIPAL INVESTIGATOR
Allan Brasier, professor of medicine and executive director of UW Institute for Clinical and Translational Research

CO-INVESTIGATORS
Shannon Kenney, professor of oncology

Jeff Johnson, professor of pharmaceutical sciences

Bo Liu, professor of surgery

Manish Patankar, professor of obstetrics and gynecology

Wei Xu, professor of oncology

Spencer Erickson, associate scientist in the School of Medicine and Public Health

John Feltenberger, associate scientist in the School of Pharmacy

COLLABORATORS
Richard Anderson, professor of medicine

Alan Attie, professor of biochemistry

Arash Bashirullah, professor of pharmaceutical sciences

Vincent Cryns, professor of medicine

Anthony Gitter, assistant professor of biostatistics and medical informatics

Jennifer Golden, assistant professor of pharmaceutical sciences

Randy Kimple, associate professor of human oncology

Paul Marker, professor of pharmaceutical sciences

Judith Smith, associate professor of pediatrics

Yongna Xing, associate professor of oncology

Jing Zhang, professor of oncology

Xinyu Zhao, professor of neuroscience