Assistant Professor in the Department of BMI, Dr. Patrick Giguère
Dr. Patrick Giguère started his research program in July 2015. He combines pharmacological, biochemical and structural approaches to develop therapeutics strategies targeting G protein-couples receptors (GPCRs) function, with enhanced therapeutic potential, while reducing their deleterious side effects.
What is your background?
After completion of my B.Sc. in Biochemistry, I was first introduced to the world of GPCR during my Ph.D. studies under the supervision of Dr. Jean-Luc Parent at the University of Sherbrooke working on thromboxane receptors. I was then recruited to the laboratory of Dr. David Siderovski at the University of North Carolina at Chapel Hill (UNC-CH), where I carried out postdoctoral studies working on a newly discovered G protein regulator, called GPSM3. This protein is selectively expressed within immune cells and was found to have critical role in the sequelae of autoimmune disorder such as rheumatoid arthritis. Following my postdoctoral training, I joined the laboratory of Dr. Bryan L. Roth, in the Department of Pharmacology of UNC-CH. Dr. Roth is an internationally recognized leader in GPCR signaling and drug discovery. During my time in the Roth lab, I acquired extensive expertise in drug discovery, molecular pharmacology and structural biology. I participated to the discovery that the presence of a sodium ion and water molecule network in a conserved cavity within class A GPCRs has an important role in GPCRs functionality.
Tell us about your research?
Living organisms sense and react to changes in their environment via cell surface receptors that collect extracellular stimuli, integrate these signals, and respond accordingly. The largest family of receptors expressed in vertebrates are called G protein-coupled receptors (GPCRs). They are by far the most extensive validated class of therapeutic targets with more than 30% of prescribed drugs. Over the last decade, pharmacological concept has evolved remarkably after the finding that different ligands, at the same receptor, can selectively activate and prefer certain signalling pathways among all pathways activated by balanced ligands. This intrinsic property of ligands, known as “functional selectivity”, has opened up the way for the generation of pharmacologically distinct drugs with enhanced therapeutic potential, while reducing their deleterious side effects. My research seeks to use a combination of pharmacological, biochemical, and structural approaches to develop a new level of understanding of GPCR molecular recognition, pharmacological and functional selectivity and develop novel classes of GPCR therapeutics.
What are some applications of your work?
One of our active working models is on opioid receptors. Opioids are among the oldest and most prescribed and abused medications. Endogenous opioids act through the activation of the three classical opioid receptors (μ, κ and δ-OR) and the related nociception/orphanin FQ peptide receptor (NOP). Substances addressing the opioid receptor system are widely used pharmaceuticals for treatment of chronic pain and addictive disorders. Mental health or addiction problems, including depression, anxiety disorders, schizophrenia, substance and non-substance abuse, are the leading causes of disability in Canada. Given the difficulties associated with opioid therapy (overdose, tolerance, addiction, respiratory depression and constipation) there is a need for safer narcotic analgesics representing one of the specific objectives of my lab. The ultimate objective of my research is to generate distinct therapeutics that will uniquely modify their pharmacology in a medically meaningful way increasing their therapeutic efficacy with reduced harmful side effects.
What got you interested in GPCR pharmacology?
Since I was around 10 years old, I have been passionate about science. I was fascinated about all aspects of living organisms and always been curious to understand how things work. When teenager, I struggled between mechanics and science. I decided to tackle the most complex machine! Once I started my bachelor in biochemistry, I knew I was at the right place and have the aptitude to success in this path. After being mentored by exceptional scientists during my undergraduate studies, I started working on G protein-coupled receptors and devoted my career to this exceptional diverse family of receptors. While having similar topography of seven transmembrane helices, each receptor is unique and represents a challenge to work with. Moreover, these receptors are involved in all physiological processes and many pathological dysfunctions and thus represent a formidable drug target to treat diseases. My postdoctoral studies opened my eyes on how exciting it is to build new tools to answer unaddressed question and the powerful of drug pharmacology. Having a diversify background, my acquired knowledge now serves me well to tackle these receptors and unlock what I believe will be the future therapeutics.
What’s the most interesting thing about you that we wouldn’t learn from your resume?
I have strong determination, while facing out some adversity through my path, I have always been determined and believed in my skills. Science takes a huge place in my life but my priorities is and will always be my family. Married to a wonderful wife, father of two tornado kids made in USA and owner of a dog, I enjoy spending time home with family and doing outdoor activities. . I am a good handy man. I can fix and build almost everything I want around the house, it just takes time! I love to have many projects on the burner. I enjoy everything that can turn off my brain to think about science, which is quite challenging sometime. I’m a big hockey fan, I don’t miss a game, but sorry, my team is the Habs! I like fiction movies where you totally disconnect from the reality. I like different types of music but my favourites are soft rock from the 80’-90’. I’m fascinated by scuba diving; spending 7 years in North Carolina gave me the chance to explore wonderful wrecks and unique environment, can’t wait to discover the great lakes area!