Joanne Murphy-Ullrich, Ph.D., Professor Emerita, Molecular and Cellular Pathology, has been inducted into UAB's chapter of the National Academy of Inventors. Murphy-Ullrich was recognized at an induction ceremony at the UAB Collat School of Business on October 11.
The National Academy of Inventors (NAI) honors the most accomplished inventors and patent holders nationwide, focusing on academic institutions and governmental and nonprofit research institutes. The NAI has more than 4,000 individual inventor members and Fellows spanning more than 250 institutions worldwide. UAB’s Bill L. Harbert Institute for Innovation and Entrepreneurship has long recognized NAI membership and officially established UAB’s NAI chapter in 2022 to recognize and encourage UAB’s community of inventors.
Murphy-Ullrich joined the Department of Pathology as assistant professor in 1991. In 1995, she was promoted to associate professor, and in 2000, she was named professor. After 37 years of service to UAB, Murphy-Ullrich retired in 2023. As a renowned researcher, she had a hand in several significant discoveries, including the identification of a cellular de-adhesive role for matricellular extracellular matrix (ECM) proteins. This function controls cell adhesion, migration and cell survival, a process called intermediate cell adhesion. She and her team discovered the role of thrombospondin-1 (TSP-1) as an activator of latent TGF-β, elucidating molecular mechanisms and the role of this pathway in disease pathogenesis (fibrosis, cancer, glaucoma, wound healing). Her lab showed the importance of this pathway in diabetic complications, including hypertensive cardiomyopathy and diabetic nephropathy, and in various vascular, pulmonary, and wound healing disorders and was involved in drug development efforts through the Alabama Drug Discovery Alliance with Southern Research.
"Our intellectual property developed from extensive basic science studies in the mid to late 1990s where we identified a four amino acid sequence in the inactive (latent) form of a fibrotic and immune regulatory growth factor, TGF-beta, that was important for binding to the extracellular matrix protein, thrombospondin-1 (TSP-1)," said Murphy-Ullrich. "This binding of TSP-1 to latent TGF-beta converts the growth factor to its biologically active form. Active TGF-beta is a major driver of fibrosis and is involved in tumor mediated immune suppression. We used the four amino acid peptide as a competitive blocker of TSP-1 binding to prevent activation. Over the years, we showed that this peptide (leucine-serine-lysine-leucine or LSKL) can prevent fibrosis in the kidney and in the heart in diabetic and hypertensive rodents."
"In 2011, we were awarded a grant from the Alabama Drug Discovery Alliance to identify a small molecule based on LSKL. Working alongside the drug discovery team at Southern Research, we identified new small molecules with better drug-like properties that mimic LSKL and showed activity in delaying progression of multiple myeloma. Currently, we are working with Orange Grove Bio and Station 41 to continue this drug development pathway. One of our therapeutic targets is renal fibrosis. To this end, Orange Grove Bio has established a new company based on this target that is called DomainOne Therapeutics. Targeting the TSP-1/latent TGF-beta pathway represents a disease-context specific approach to controlling inappropriate TGF-beta activity, while sparing the necessary, beneficial levels of TGF-beta activity."