Mentors and the butterfly effect: triggers for discovering signalling by proteinases via proteinase-activated receptors (PARs) and more.

Contributors: Morley Hollenberg Research Group
Clin Invest Med. 2012 Feb 1;35(6):E378-91.


The essential role of proteinases as regulatory digestive enzymes, recognized since the late 1800s, has been underscored by the discovery that more than 2% of the genome codes for proteinases and their inhibitors. Further, by the early 1970s it was appreciated that in addition to their digestive actions, proteinases can affect cell function: (1) by the generation or degradation of peptide hormones and (2) by the direct regulation of signalling by receptors like the one for insulin. It was the discovery in the 1990s of the novel G-protein-coupled ‘proteinase-activated receptor’ (PAR) family that has caused a paradigm shift in the understanding of the way that proteinases can regulate cell signalling. This overview provides a perspective for the discovery of the PARs and my laboratory’s role in (1) understanding the molecular pharmacology of these fascinating receptors and (2) identifying the potential pathophysiological roles that the PAR family can play in inflammatory disease. In this context, the overview also portrays the essential impact that seemingly minor comments/insights provided by my lifelong mentors have had on kindling my intense interest in proteinase-mediated signalling. The ‘butterfly effect‘ of those comments has led to an unexpectedly large impact on my own research directions. Hopefully my own ‘butterfly comments’ will also be heard by my trainees and other colleagues with whom I am currently working and will promote future discoveries that will be directly relevant to the treatment of inflammatory disease.



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Congratulations to first place winner Doug Brown!

Congratulations to PhD grad student Doug Brown for his First Place win at the 2018 University of Alberta Student Falling Walls Lab Competition! Doug’s First Place award also gains him an entry and an all-expenses-paid trip to the highly competitive and prestigious Falling Walls Lab Conference in Berlin, November 8-9, 2018!

Fifteen student presenters pitched their innovative and globally-important research ideas in a short 3 minute presentation to a panel of science and tech-business savvy judges and a large cheering audience on September 19, 2018, at the University of Alberta in a high-stakes “TEDTalk” meets “Dragon’s Den” style. The competition was very strong but Doug gave an inspired speech on breaking down the walls of metastatic cancers using new lipid nanoparticle technology that he is helping to develop during his graduate studies in Dr. John Lewis’ laboratory.

The Sept 19th UofA Falling Walls Lab competition will be featured on Global News on the evening of Sept. 20th, around 6:15 pm. Check it out!

Doug will be taking his pitch to the Falling Walls Lab competition in Berlin, Germany this November where he will compete with many other inspirational students at this international event.

This is doubly exciting for the Lewis lab because John Lewis recently won the UofA Falling Walls Venture competition that was held on Aug 29, 2018 and he will be competing in the Berlin Falling Walls Venture!

Good luck to both Doug and John at the Falling Walls Finale in Berlin!

- Perrin Beatty