Discovery and development of Selonsertib, a first in class inhibitor of ASK1 for the treatment of nonalcoholic steatohepatitis
Time: 10:00 am
- Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that is expected to become the leading cause of cirrhosis and liver transplantation.
- There is a large unmet need for therapies that can reverse liver fibrosis due to NASH, there are no approved drugs.
- Apoptosis signal regulated kinase 1 (ASK1) is a serine threonine kinase that couples oxidative stress to the activation of pathways that promote hepatocyte apoptosis, inflammatory cytokine production and fibroblast activation.
- A drug-discovery campaign was initiated to identify novel small molecule inhibitors of ASK1, leading to the discovery of selonsertib, which is undergoing testing now.
David Breckenridge is a Senior Director of Biology at Gilead Sciences Inc. and oversees research and strategy for fibrotic diseases including nonalcoholic steatohepatitis (NASH) and diabetic kidney disease (DKD). Over his 10 years in industry, Dr. Breckenridge has led projects from early discovery through phase 1 clinical development and has supported multiple discovery and development efforts across fibrosis, inflammation and oncology. He was the project lead for Selonsertib, a novel first in class inhibitor of ASK1, which is currently in phase 3 clinical trials for NASH and being developed for additional fibrosis indications such as DKD. He attained a BSc. in biochemistry from Dalhousie University and a PhD in Biochemistry from McGill University. Dr. Breckenridge conducted post-doctoral research in the department of Molecular, Cellular and Developmental Biology at the University of Colorado at Boulder where he focused on molecular mechanisms of apoptosis.
Three short stories on survival in the age of CRISPR/Cas9
Time: 4:00 pm
- Dr. Edgell will briefly describe his lab’s role in the development of genome-editing nucleases derived from mobile genetic elements, particularly from the I-TevI endonuclease, and how fusion of I-TevI to different DNA-binding proteins creates novel genome-editing nucleases.
- Improvements to the functionality of the popular Cas9 nuclease by making hybrid TevCas9 nucleases to control deletion length made during genome editing will also be highlighted, as will applications of the TevCas9 nuclease in algal genome engineering and microbiome control.
David Edgell earned his BSc in Biochemistry & Microbiology at the University of Victoria and PhD from Dalhousie University in Ford Doolittle’s laboratory. He then went on to complete post-doctoral studies with Marlene Belfort and David Shub at the Wadsworth Center, New York State Department of Health and State University of New York (SUNY) at Albany. In 2003, he joined the Department of Biochemistry, Schulich Medicine & Dentistry as an Assistant Professor and was appointed as an Associate Professor in 2009. He is currently Acting Chair of the Department of Biochemistry. Dr. Edgell is the recipient of several awards including a Postdoctoral Fellowship from the Canadian Institutes of Health Research; an Early Researcher Award, Government of Ontario; a New Investigator Award from the Canadian Institutes of Health Research; the Dean’s Award of Excellence, Junior Faculty, Schulich School of Medicine & Dentistry; and a Faculty Scholar Award. Dr. Edgell maintains an active research program in the areas of genome engineering and synthetic biology. His research is supported by grants from the Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and Ontario Genomics.