Gary Cline, PhD, professor (endocrinology); director, Analytical Core, Mouse Metabolic Phenotyping Center; and co-director, Clinical Metabolism Core, Yale Diabetes Research Center, has retired, effective July 1, 2021.
“Much of my decision to retire has to do with a growing family. We have grandchildren that we want to be closer to so we're thinking of moving to be closer to them,” explained Cline. “Retiring also gives me the time to pursue other interests, like environmental studies and ecology. I'd like to pursue that more, and just be out, exploring nature, camping, canoeing, and other outdoor activities.”
Cline earned his Bachelor of Science degree in biochemistry from the University of Missouri-Columbia, during which time he served in the United States Coast Guard. After his honorable discharge in 1984, he earned his PhD in chemistry from the University of Missouri-Rolla in 1988. Cline came to Yale School of Medicine (YSM) for his postdoctoral fellowship in the Department of Chemistry under the tutelage of Martin Saunders, PhD. The original plan was to stay in New Haven for two years, but a chance meeting with Gerald I. Shulman, MD, PhD (George R. Cowgill Professor of Medicine (Endocrinology) and Cellular & Molecular Physiology), changed that timeline.
“I was working with Dr. Saunders in the chemistry department doing some very basic and fundamental chemistry, and using different stable isotopes to investigate chemical rearrangements, and combining the experimental empirical observations with high-level, theoretical calculations,” said Cline. “Part of that work involved a lot of NMR and MS time. At the time, the NMR and Mass Spec facilities were shared resources, so people every Friday morning would meet together, and put in their request for time. One of those people that was putting in a request for time was Jerry Shulman. We shared ideas about what we were doing with our research and he asked if I would be interested in helping run some samples for him. I said I was happy to do that.”
After a few months, Cline was recruited over to YSM and joined Shulman’s lab as an associate research scientist. Shulman had recently arrived at Yale.
“I was in the process of establishing gas chromatographic-mass spectrometer methods at Yale so that we could use stable isotopes to assess glucose, lipid, and protein metabolism in humans instead of radiolabeled isotopes, which were the only type of isotopes used at Yale at that time,” explained Shulman. “In those days, the only gas chromatographic-mass spectrometer available at Yale for these stable isotope analyses was located in the Department of Chemistry, so I had to bring my samples up to Science Hill for these analyses and run them myself. This is where I first met Gary and learned of his interest in biology and biochemistry. Given his strong background in physical/organic chemistry and my interest in developing new GC-MS and LC-MS/MS methods to probe intracellular metabolism in humans and animal models of metabolic disease, it was an easy decision to invite Gary to join my team. It was this chance meeting that led to a wonderful and successful 35-year collaboration.”
At the time, the lab, due to Cline’s contribution, was developing the mass spectroscopy by doing a lot of in vivo work with animal systems. “A major distinguishing aspect of the work, was that it involved everything from the cell work to animal work, to humans, and so we did a lot to develop the methodologies to run the gamut from cell culture to in vivo spectroscopy in animals and humans. I was fortunate to step into this translational research from animals to people,” said Cline.
His work was also instrumental in achieving National Institutes of Health sponsorship for Yale’s Mouse Metabolic Phenotyping Center (MMPC), which Cline led the Analytical Core. Their work complemented the efforts of the Diabetes Research Center.
“All of this is really a team effort, and I was just very fortunate to be able to work with Jerry Shulman, Inger Magnuson, Doug Rothman, Bob Sherwin, Bill Tamborlane, Sonia Caprio, and many, many others. It was just worked out to be a good opportunity, and I happened to be there at the right time,” Cline commented.
Through this work at the MMPC, Cline met David H. Wasserman, PhD, Annie Mary Lyle Chair; professor (molecular physiology and biophysics); and director, Mouse Metabolic Phenotyping Center at Vanderbilt School of Medicine. The pair shared best practices on running their respective MMPCs.
“I knew Gary by reputation, but met him for the first time in Washington D.C. at the first meeting of the Mouse Centers Consortium in September of 2001. It was about five days before 9/11. Gary came with Jerry Shulman as part of the Yale contingency to this consortium,” recalled Wasserman. “I've had the pleasure of knowing him and working with him since that time. Gary was an asset to the Mouse Centers Consortium and having the opportunity to work with him was a rewarding experience. l’ve come to realize that it’s the people I’ve met in my life in science that I will remember most. Gary’s commitment to excellence and his openness in sharing new ideas made him amongst my most valued colleagues.”
“Gary’s background in chemistry created an important place for him in the diabetes research community. He brought sophisticated chemical theory and practice to studies of physiology in vivo. This was important to the program at Yale and in a broader sense to advances to the field of metabolism. He was a physical scientist who was willing to tackle physiology. This made him a powerful resource,” Wasserman continued.
Due to his background in biochemistry, Cline does look at diabetes from the molecular level, from intracellular questions up to integrated physiology. “Gary has been an important member of the metabolism research community at Yale and, indeed, across the world. He has had longstanding partnerships with members of the Endocrine Section to develop innovative techniques combining classical and novel metabolic tracers with advanced imaging techniques. These new methods, in turn, have allowed detailed study of metabolic pathways in animal models and in people. His efforts have helped us better understand basic processes of carbohydrate and fat metabolism and how normal physiology becomes dysregulated in diseases such as diabetes and obesity. Ultimately, these studies have been and will be key building blocks towards better therapies for patients,” said John Wysolmerski, MD, section chief (endocrinology & metabolism).
Through the MMPC, Cline also became friends with Maren R. Laughlin, PhD, senior advisor for Integrative Metabolism in the Division of Diabetes, Endocrinology and Metabolic Diseases at the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases, who considered Cline a ‘joy to work with.”
“He's very responsible, he always pitches in to work with everybody. He's a kind, lovely, warm person,” said Laughlin. “He's an outstanding technologist who produces reliable results. He is a smart engineer, and a quantitative chemist. The MMPC works as a consortium with a mission to help scientists all across the country, and Gary rose to every occasion and made himself valuable in many different ways. Gary definitely helped create a friendly, collaborative, productive community. Everybody trusts and likes to work with Gary.”
Laughlin tapped Cline’s expertise to teach a course through the consortium on tracer technology, which he did for over 15 years, for about 100 students annually. The duo also partnered on beta cell and pancreas imaging. Overall, Laughlin has been impressed with Cline’s breadth of expertise.
“You don't usually find one person who can be innovative in many different kinds of technology. Gary is not only highly proficient, but he also takes on difficult, highly significant research projects. In order to measure pancreatic beta cell mass in people, he implemented challenging time-dependent PET approaches and developed novel ways to analyze the data. Along with Richard Carson [PhD] and Jason Bini [PhD], he actually identified a neuroimaging agent that appears to work well for the very difficult task of imaging the beta cell.”
Growing up, he was always interested in science. Fascinated by the famous French explorer Jacques Cousteau, Cline and his brothers would roam the woods of rural Missouri, and find fossils in dry creek beds. Back then, Cline hadn’t imagined a career in endocrinology and metabolism.
“When I started working in metabolism in 1988 or 1989, I thought everything was known, and it fairly quickly became clear how much was still to be discovered,” he said. “I think we have a tendency to think that at this point that everything is still known, but in reality, there's so much that we still need to sort out, there's a lot of challenges left to work on, to really understand how the body works, and endocrinology is a major part of that, regulating the body to stay healthy.”
Richard Kibbey, MD/PhD, associate professor of medicine (endocrinology) credits Cline for shepherding his career. “I've known Gary since 2002. He took me under his wings and showed me the ropes and taught me a lot about beta cells. I was a complete newbie to the field, so he got me started on the basics of how to work with beta cell lines and how to measure insulin secretion. Much more complicated, he also introduced the field of stable isotope labeling and metabolic flux. We worked very hard on a project using NMR to measure ATP synthesis in real time in living beta cells in response to glucose that was foundational for a manuscript on the role of mitochondrial GTP in glucose sensing that we was published in Cell Metabolism. He's always been there to provide not only technical insight but also to remind me of the big picture in metabolism,” said Kibbey.
Wasserman also credited Cline’s contributions to the field. “Gary had a very productive and had many contributions as a primary investigator in the area of pancreatic biology and the metabolism of the insulin-secreting beta cells, and in imaging the pancreas. No one was imaging the pancreas, and Gary took that on, and with his knowledge and the facilities there, he made significant inroads into better understanding an untouched area of beta cell biology. I think he would be most proud of his contributions in that area,” said Wasserman.
His departure leaves a huge hole in the section. “We'll have to see how it goes, but it's going to be a major, major shakeup,” said Kibbey. “In addition to being a great captain, mentor, and friend, he really was instrumental in supporting so many projects, groups, instruments, ideas, whatever, so I'll miss him. I'll really miss him.”
“While his presence will be missed in the Endocrine Section, his gracious and patient tutoring of many trainees over the years will allow his work to go forward in many exciting directions,” said Wysolmerski.
Shulman noted that Cline’s footsteps would be impossible to fill. “For the past 35 years, Gary has been a critical member of an interdisciplinary team of scientists that have allowed us to address critical questions relating to the regulation of intermediary metabolism in humans and transgenic rodent models of metabolic disease. These studies have provided us with new insights into the pathogenesis of insulin resistance and type 2 diabetes which in turn has led to the identification of new therapeutic targets and drugs for the treatment of diabetes, lipodystrophy, nonalcoholic fatty liver disease, and non-alcoholic steatohepatitis that would not have happened without him. Although we will try our best I think it will be impossible to fill Gary’s footsteps – he is one of a kind. However, I am hopeful that Gary will still be interested in future collaborations as an Emeritus Professor of Medicine, while he explores nature, pursues environmental studies, and spends more time with his grandchildren,” said Shulman.
Cline and his wife of 39 years, Rebecca, have three children, Jeremy, Patrick, and Emily. Upon his retirement, Cline was granted emeritus status from Yale University.
Yale’s Section of Endocrinology & Metabolism works to improve the health of individuals with endocrine and metabolic diseases by advancing scientific knowledge; applying new information to patient care; and training the next generation of physicians and scientists to become leaders in the field. To learn more about their work, visit Endocrinology & Metabolism.