Clinician-scientist continues groundbreaking discovery in diabetes research

Today’s research continues to rapidly accelerate, driven by the availability of new cutting-edge tools tied to single-cell sequencing, proteomics, and highly evolved computer-based bioinformatic analyses.

Even before coming to UCSF, Suneil Koliwad, MD, PhD, was in awe of the discoveries of Gerold “Jerry” Grodsky, PhD, now professor emeritus in the UCSF Diabetes Center. Grodsky’s pioneering work that illuminated the mechanisms involved in the synthesis, storage, and secretion of insulin, has made him among the most celebrated scientists in the world of diabetes research. Today, Koliwad follows in Grodsky’s footsteps as chief of the Division of Endocrinology and Metabolism and the Gerold Grodsky, PhD/JAB Distinguished Professor of Diabetes Research at UCSF. 

An anonymous donor and friend of the UCSF Diabetes Center established Koliwad’s professorship in Grodsky’s honor in 2010. Last year, the individual generously elevated this support to a distinguished professorship.  

“Because of the new Grodsky professorship, I'm able to lead the clinical mission of the Division of Endocrinology and Metabolism while continuing to pursue an ambitious research program,” says Koliwad. “This support provides me with crucial resources at exactly the right time.” 

Koliwad decided to dedicate his career to preventing type 2 diabetes when he was a combined internal medicine and pediatrics resident at Baylor College of Medicine. There, he saw firsthand the burgeoning epidemic of obesity that was looming on the horizon. He came to UCSF in 2003, first to pursue a fellowship in diabetes, endocrinology, and metabolism, and later accepting a postdoctoral fellowship in the UCSF-affiliated Gladstone Institute of Cardiovascular Disease.  

During his postdoctoral research, Koliwad discovered that the ability of macrophages – a type of immune cell – to store dietary fat within fat tissues in obesity was a determinant of the development of a form of inflammation linked closely to the progression of type 2 diabetes. On the heels of this groundbreaking work, he chose to begin his faculty career and start his own research lab at the UCSF Diabetes Center.  “Coming to the UCSF Diabetes Center was a chance to continue a history of game-changing research that was heavily influenced by Jerry,” says Koliwad, whose lab today on UCSF’s Parnassus Heights campus investigates cellular and molecular drivers of obesity, insulin resistance, diabetes, and the impact of excessive fat accumulation in multiple organs. Grodsky’s foundational discoveries at UCSF almost six decades ago, which has informed the design of an artificial pancreas and transformed the treatment and lives of people with diabetes, occurred more by chance than design. Grodsky was not a clinician, and initially, he had no patients to learn from. Instead, he began studying insulin in the Metabolic Research Unit (MRU) at UCSF because he was a chemist, and insulin was “the purest protein that you could get in a bottle.” From there, his interest in insulin grew into a singular scientific focus.

Collaboration and cross-disciplinary research were not always a part of UCSF’s culture, according to Grodsky, who came to the university in the early 1960s. “Any collaborations at that time between a scientist with a PhD background and a clinician happened only because two people decided they liked each other, trusted each other, and wanted to work together,” he says. “Not because universities encouraged it.”

In fact, most medical schools then had very little cross-fertilization between basic scientists and clinicians, but Grodsky managed to make it happen, as did others in the MRU. In fact, he and his clinician colleagues worked together to make some of the seminal discoveries about what disrupts insulin's actions in the body during the earliest stages of diabetes. Their findings were particularly crucial to understanding the effects of those actions on the pancreas, where insulin is made, and the liver, a key metabolic organ that responds to insulin. Diabetes occurs either when the pancreas doesn’t make enough insulin or when organs like the liver no longer respond to it properly.

“In those days, diabetes was a hidden disease,” Grodsky explains. “People didn’t want to talk about the fact that they had diabetes. We had no Diabetes Center of any kind. I was a biochemist doing what seemed most natural to me: choosing a protein – insulin – because it was the best model I could find for my research.”

The whole field has benefited from the fact that Jerry viewed insulin as a very approachable molecule for synthetic chemistry,” says Koliwad. “When I started as an assistant professor, I was surprised to find out that a professorship was going to be attached to the position. When I saw that it was in Jerry’s name, I thought, ‘OK, this is not by chance. This is fate.’

Grodsky and his group used a novel radioimmunoassay technique, which they pioneered in humans, to reveal that insulin is released in phases by the pancreas. This was a significant finding and led to the understanding that insulin, for diabetes patients who were not manufacturing it for themselves, would have to be pumped into the body in stages to have the desired effect.

For the first time, scientists were able to measure small amounts of proteins, like insulin, in biological fluids. “Almost every Monday, we'd get the results of the experiments from the week before. Nobody had ever been able to do what we were doing. It was an exciting time for me and my lab,” recalls Grodsky.

Koliwad appreciates the connection between what was happening in Grodsky’s world in the 1960s and what is going on now. Today’s research continues to rapidly accelerate, driven by the availability of new cutting-edge tools tied to single-cell sequencing, proteomics, and highly evolved computer-based bioinformatic analyses – just as Grodsky’s research was hastened by the development of a new radioimmunoassay technique and, later, by the expansion of molecular biology.

In his new leadership role as chief of the Division of Endocrinology and Metabolism, Koliwad seeks to build on strong collaborations across UCSF to help his team achieve scientific breakthroughs that will improve the lives of his patients. The name of the game at UCSF these days, according to Koliwad, is collaboration. “It is central to what we do and how we approach complex problems on behalf of our patients,” he says. For his team, it includes partnerships with UCSF Health, the Diabetes Center, the Cardiovascular Research Institute, the Bakar ImmunoX initiative, the Bakar Computational Health Sciences Institute, the newly emerging Bakar Aging Research Institute, and the Benioff Center for Microbiome Medicine.

There is remarkable continuity between what I am doing in my lab now and what Jerry did during his career,” says Koliwad. “The fact that this professorship in diabetes research is named in Jerry’s honor brings that continuity full circle for me.