In Memory of Dr. Marc G. Caron

It is with grief and fondness that we memorialize Dr. Marc G. Caron, Ph. D., who passed away unexpectedly on Monday, April 25, 2022. Dr. Caron was a Canadian/American scientist who was the James B. Duke Professor of Cell Biology, Professor of Neurobiology and Professor of Medicine at Duke University Medical Center. During his 50-plus year scientific career, he authored more than 650 publications and served as Editor-in-Chief of Endocrine Reviews, Associate Editor of Biochemistry and as a Board Member for JBC, JCI and several other prestigious journals. A native of St-Cyrille de L’islet, Quebec, Canada, Marc completed his undergraduate studies in Biochemistry at Laval University Quebec in 1969 and obtained a Ph.D. in Biochemistry from the University of Miami in Miami, Florida in 1973. He then moved to Durham, North Carolina to conduct post-doctoral training at Duke University Medical Center from 1973-1975. In 1975, he joined the Department of Physiology at Laval University as an Assistant Professor. After just two years at Laval University, Marc chose to return to Duke University where he quickly rose through the ranks to become a Full Professor and the James B. Duke Professor of Cell Biology. Among his many honours, Dr. Caron was an Investigator of the Howard Hughes Medical Institute from 1992 to 2004, a member of the American Academy of Arts & Sciences and a fellow of the American Association for the Advancement of Science. In 2005, he received the Julius Axelrod Award from the American Society for Pharmacology and Experimental Therapeutics. The Julius Axelrod award recognized his major impact towards understanding the pharmacological actions of drugs and his contributions to the field by mentoring and training of pharmacologists that have become recognized leaders in the field. As expected, and given his illustrious career, it is not surprising that there are already several excellent eulogies that have been written to commemorate him and to describe various aspects of his significant scientific and personal impact (Caron and Dzirasa, 2022; Kuhn and Krishnan, 2022; Lefkowitz and Amara, 2022; Roth, 2022; Bohn LM, unpublished). For the audience of International Journal of Neuropsychopharmacology, we chose to focus on Marc’s contributions to the field of neuropsychopharmacology and his impact on the field through his mentorship and training of so many scientists who are actively involved in biomedical research. Marc made major contributions to distinct yet complimentary fields of research: the field of GPCR biology and the field of neurotransmitter receptors and transporters, with a special focus on the dopamine system. His contributions to the field of GPCR’s began in the 1970’s where he was instrumental in pioneering the biochemical techniques that allowed the pharmacological characterization, purification and cloning of the β2-adrenergic receptor in 1986. His laboratory and others went on to clone many other important GPCRs demonstrating that GPCRs represent a superfamily of transmembrane receptor proteins. Dr. Caron was also a leader in the identification and characterization of G-protein-coupled receptor kinases (GRKs) and β-arrestins. Studies from his laboratory further showed that β-arrestins were not only involved in receptor desensitization, but that they were also involved in GPCR endocytosis and in the activation of non-canonical intracellular signaling pathways beyond the G-proteins. In parallel to his work on GPCRs, Dr. Caron also made seminal contributions to the field of neurotransmitter transporters. Most notably his laboratory generated the first genetically modified mouse lacking the dopamine transporter (DAT-KO). His studies provided a previously unknown important understanding of the role of dopamine transport in the regulation of dopamine homeostasis relevant to neuropsychiatric disease. His laboratory (with various collaborators) further generated and characterized mice with knockout mutations of other key monoaminergic regulators including NET, VMAT2, GRK2, GRK6, β-arrestin-2, and TPH2. Much insight about the contributions of these proteins in regulating neurotransmission has been gained over the years through the detailed and ongoing characterization of these animals. This work has been the topic of many highly-cited review articles and included in Neuro/Pharm/Physiology textbooks. In the 2000’s, his lab focused on dopamine receptor signaling and pioneering studies from his team identified a novel mode of signaling for dopamine D2 receptors involving β-arrestin2. His group showed that selectively targeting this D2/β-arrestin2 pathway, using biased compounds, might lead to identification of better antipsychotics with reduced adverse effects. The concept of biased signaling has been an important topic of research of many scientific groups for the past 15-20 years. The Caron group was at the forefront of the field of β-arrestin signaling contributing to key important publications and studies within the field of biased signaling. In addition to all of these fundamental scientific contributions, Marc was an outstanding scientific mentor. He encouraged collaborations within the lab and facilitated collaborations across the globe. He encouraged complete, multidisciplinary studies in his publications and told his trainees that a good paper would be cited regardless of the journal’s name. He was happy to publish in journals that were connected to societies, and it was often his postdocs that sought the “big-name” journals. There were many manuscripts where Marc would gather the authors together in his office to read the manuscript aloud, “with feeling”. His insightful edits elevated many papers beyond the original scope that his trainees envisioned. Marc also created a welcoming, supportive, inclusive and diverse lab. During our years of training in the lab, we were lucky to have colleagues with diverse scientific specializations representing several nationalities and cultures. One particular group of trainees often outnumbered the others because of Marc’s French-Canadian Heritage. His lab would attract an unusually high number of Canadian and francophone trainees. At any given time, there would be at least 2-3 Canadian and/or french-speaking trainees. He supported the success of his trainees by helping them secure independent grant funding and allowed trainees to serve as senior author on papers of students and postdoctoral fellows that they trained and supervised. He shared biological reagents (and mouse models) with no strings attached. He would drop everything to connect trainees with experts in the field to advance science. This was all done from an angle of love for science and genuine support for the success of everyone who passed through the lab. On a personal level, Marc was a devoted family man and would always make time for family meals and function. This aspect was extended to his trainees, where Marc, his late wife Pauline and the rest of his family would open their house to newly arrived trainees to make them feel welcome in Durham, an aspect that was greatly appreciated especially by foreign trainees who were new to North Carolina and the US. This sense of community has led many of the trainees to speak of the greater Caron Lab Family. To conclude, Dr. Marc G. Caron is remembered as a most gifted experimentalist and an awe-inspiring mentor who opened exciting new vistas in neuropsychopharmacology and opportunities for his trainees. For his loss, we extend our sincerest condolences and heart felt grief to Dr. Marc G. Caron’s beloved family, his dear friends, and his vast number of scientific colleagues. Few are as well loved and missed as Dr. Marc G. Caron. May Marc and Pauline rest together in peace.

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