For more than 50 years, Vanderbilt has been a global leader in the quest to understand, prevent, and treat diabetes
By Rachel Nuwer
Alan Cherrington still clearly remembers the day that unexpectedly led him to what is today the Vanderbilt University School of Medicine Basic Sciences, where he is now a professor of molecular physiology and biophysics. It was 1972, and Cherrington was a doctoral candidate at the University of Toronto. He was finishing work developing a novel experimental animal model that would offer greater insight for understanding human metabolism and already had a postdoctoral position lined up in Switzerland.
Those plans changed when Cherrington met Dr. Charles Rawlinson “Rollo” Park, a pioneering diabetes researcher from Vanderbilt who was the first to prove that insulin could stimulate the transport of glucose into cells. Park was chair of what was then called the Department of Physiology—now the Department of Molecular Physiology and Biophysics—and had come to the University of Toronto to give a guest seminar. But he was also on the lookout for promising recruits to bring back with him to Nashville.
In a one-on-one meeting with Cherrington, Park made a convincing case that the research being done at Vanderbilt was “world class” and that Vanderbilt was “one of the best places to come and study diabetes.” Park discussed his colleagues’ plans to establish the country’s first diabetes research center with support from the National Institutes of Health, and talked about his lab’s efforts to understand the molecular details of how diabetes causes glucose metabolism to go awry. He also highlighted the Nobel Prize in Medicine or Physiology that Dr. Earl Sutherland, a professor of physiology in the Vanderbilt School of Medicine, had just won the year before for decoding the mechanics of hormonal action.
Park ultimately delivered a proposition that would change Cherrington’s life: “Come to Vanderbilt.” Cherrington and his wife gave in, canceled their plans for Switzerland, and moved to Nashville instead. Their two-year stay turned into 52 years and counting—a decision that Cherrington views as one of the best he’s ever made.
Connecting the past to the present—and beyond
A direct line can be drawn from the pioneering diabetes research conducted at Vanderbilt in the early days and the world-class work that continues today—including through the recent recruitment of new investigators in diabetes-related basic and clinical science. “Decades of knowledge and know-how are concentrated here,” said Rafael Arrojo e Drigo, an assistant professor in molecular physiology and biophysics who was recruited in 2020.
“Diabetes involves or affects many different organs—the brain, liver, kidney, and pancreas—and it involves genetics, signaling pathways, physiology, developmental biology, and the environment,” said Dr. Alvin Powers, professor of molecular physiology and biophysics and medicine. It is a multifaceted disease with multiple causes that does not affect everyone in the same way.
Researchers such as Maureen Gannon, professor of molecular physiology and biophysics and medicine and associate dean for faculty development at the Vanderbilt University Medical Center, focus their investigations on understanding what drives the differences in how diabetes manifests in different people with the aim of better tailoring interventions. “Can we identify those people who would benefit from a certain treatment, instead of going through the trial and error of trying five different things before seeing what hits?” Gannon said. “Vanderbilt is in a really good position to lead in this area.”
Vanderbilt researchers study diabetes at every level, from the molecular underpinnings of insulin production and secretion across a cell’s lifetime, to the overlap between diabetes and comorbidities and complications like obesity, cardiovascular disease, aging, and Alzheimer’s disease. Researchers here are developing new paradigms for treating and preventing type 1 and type 2 diabetes, including through work on pancreatic islets, the clusters of cells in the pancreas that produce hormones that regulate blood sugar levels; techniques for preventing the immune system from destroying insulin-producing beta cells; investigations into the potential to revive “exhausted” beta cells in the pancreas; and studies on the mechanism of action for medical weight loss drugs like Ozempic.
They also conduct translational and population-based research in subjects like healthcare inequity, cost and delivery. “Talking about diabetes and its causes and clinical care must also include consideration of the social determinants of health and health equity,” Powers said.
A legacy of excellence
Vanderbilt became a leading institution for diabetes research thanks in large part to the efforts of early leaders like Park who actively recruited top-tier and up-and-coming scientists alike. Sutherland, for example, was recruited by Park and conducted some of his 1971 Nobel Prize-winning work on a molecular phenomenon called the second messenger theory while at Vanderbilt. Tetsuro Kono, who discovered the molecular transporters responsible for moving glucose into cells, and Dr. John Exton, who worked on gluconeogenesis—one of the ways the liver produces glucose—were two additional key recruits.
“A lot of early work done here was centered around how hormones work on cells,” said Roger Colbran, vice chair of the Department of Molecular Physiology and Biophysics. “To a large extent, efforts at Vanderbilt deciphered many key actions of hormones, including insulin and how it works to increase glucose flux into cells.”
In 1965, Dr. Oscar Crofford, a clinician and investigator who conducted research on how fat cells contribute to diabetes, became Vanderbilt’s first full-time diabetes specialist. He spearheaded and was the principal investigator for a pioneering clinical trial called the Diabetes Control and Complications Trial that proved that many diabetes complications could be mitigated by tightly controlling the patient’s blood glucose levels.
In addition to his research excellence, Crofford’s other claim to fame was the role he played in creating the Diabetes Research and Training Center, an NIH-supported hub that brings together basic and clinical scientists across different disciplines in the common pursuit of improving the understanding, prevention, and treatment of diabetes and its complications.
Crofford and others lobbied Congress to mandate funds for diabetes research, and, in 1973, these efforts contributed to the National Institutes of Health announcing the creation of a series of Diabetes Research Centers. Vanderbilt’s DRTC was the first of what are now 17 such centers around the country. Working with Dr. Rod Lorenz, a pediatric endocrinologist who studied how to best deliver insulin to and care for diabetes patients, Crofford ensured that the DRTC had a strong clinical focus to complement and enhance the basic science research headed by Park, Sutherland, and others.
The DRTC quickly became a major draw for even more diabetes-related talent to come to Vanderbilt, especially because of the center’s mission to facilitate career development of junior investigators. The DRTC is now home to five diabetes-related training grants for medical and graduate students and postdoctoral fellows, one of which was just renewed in August. “This T32 grant, which provides funding to support students and postdoctoral fellows who are working at the interface of engineering and diabetes, fits perfectly into our efforts to train the next generation of scientists in diabetes,” Powers said.
The DRTC also awards seed money for early-stage diabetes-related projects with an emphasis on work proposed by new investigators in the field. The center sets aside funding for enrichment programming as well, including hosting guest seminars and mini meetings, such as Vanderbilt’s annual Diabetes Research Day.
When Dr. Daryl Granner, a leading pioneer in molecular biology, was recruited to replace Park as chair of the Department of Physiology in 1984, he added a new emphasis on developing cutting-edge molecular biological and biophysical tools to study gene expression and other signaling processes. After Crofford’s retirement, Granner became the director of the DRTC and oversaw the creation of several research cores—facilities with expert-managed technologies in specialized techniques like genomics and microscopy.
In 2001, the DRTC got another upgrade when then-Associate Professor and Professor David Wasserman from the Department of Molecular Physiology and Biophysics were awarded an NIH grant to create a new center that would provide experimental services in mouse models of diabetes and related metabolic diseases. Since then, the Vanderbilt Mouse Metabolic Phenotyping Center has performed sophisticated experimental services in collaboration with investigators across the U.S. Wasserman served as the VMMPC director from its founding until his death last June. Under his leadership, around 250 visiting researchers came to learn phenotyping techniques from Vanderbilt facility.
Julio Ayala, associate professor of molecular physiology and biophysics, was selected to replace Wasserman earlier this fall. He said that Wasserman’s efforts to share the VMMPC’s expertise amplified Vanderbilt and the DRTC’s role in driving diabetes and metabolism research around the world. “That excellence continues today,” Ayala said.
A culture of collaboration
Vanderbilt and VUMC split into separate entities in 2016, but researchers at both institutions have continued strong collaborations. In some ways, Ayala said, diabetes research has been “the glue to maintain those interactions.” The DRTC has more than 140 members from 15 departments across both campuses.
The blend of basic and clinical science also highlights the DRTC’s “commitment to bringing these two overarching approaches together,” said Dr. Nancy Carrasco, the Joe C. Davis Chair of the Department of Molecular Physiology and Biophysics. Both basic and clinical research “are essential to making fundamental scientific breakthroughs that can be translated into newer, better strategies for improving patient health,” Carrasco said. This unified approach amplifies the impact that either research avenue could have on its own: Being proximate to clinicians helps basic researchers stay focused on problems that are relevant to patients and doctors, and interacting with basic researchers gives clinicians a deeper knowledge of the underpinnings of the diseases they’re treating.
According to Gannon, these interactions are also boosted by a genuine spirit of collaboration that permeates the diabetes community at both Vanderbilt and VUMC. “I was a skeptical New Yorker when I came here, but it really is true that we have a culture of collaboration and collegiality,” she said. “You can’t move forward in understanding diabetes and finding new pathways for prevention and cures if everyone is in their own lab not talking to anyone.” Gannon said that Vanderbilt and VUMC researchers “share ideas, help each other, give advice, and critique each other,” and, as a result, of the more than 500 diabetes- and obesity-related papers published by Vanderbilt groups in the last five years, half had more than one DRTC investigator as an author.
Vanderbilt has continued its role as a leader in diabetes research on the national and international level as well. DRTC members have been heavily involved with both the Juvenile Diabetes Research Foundation and the American Diabetes Association. According to Cherrington, the president of the American Diabetes Association is “the authority figure around the world in diabetes”—a position that he, Crofford, and Powers have all held.
Vanderbilt’s campus continues to bring researchers from multiple institutions together. From 2001 to 2015, Dr. Mark Magnuson, professor of molecular physiology and biophysics, headed the NIH-funded Beta Cell Biology Consortium, a group of researchers who sought to understand how beta cells develop and eventually fail. That program’s success led to a second, currently active consortium, the Human Islet Research Network, whose investigators now work to better understand immunology and other aspects of type 1 diabetes. HIRN comprises investigators from Vanderbilt and other institutions, which has helped spread Vanderbilt’s influence to a broader group of scientists.
As Arrojo e Drigo said, “If you were to draw a map and link all the diabetes researchers in the U.S., a lot of them would link to Vanderbilt in one way or another.” He predicts that, in the coming years, those links will only become richer.
“That’s why I originally came here: to be in a place that’s always been and continues to be at the forefront of diabetes research,” Arrojo e Drigo said.
Diabetes is a terrible disease that causes suffering and death in a growing number of people throughout the world. And yet there is hope thanks to the tireless work of diabetes and metabolism researchers, work that has led to profound breakthroughs that have improved patients’ lives throughout the last century. And if the growing impact of a new generation of drugs that treat diabetes is anything to go by, the next century promises even a bigger revolution.