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Dr. Alan R. Saltiel is Distinguished Professor of Medicine and Pharmacology, Maryam Ahmadian Endowed Chair in Metabolic Health, Director of the Institute for Diabetes and Metabolic Health at UC, San Diego, and Director of the UCSD/UCLA Diabetes Research Center. He received his bachelor’s degree in zoology from Duke University, and his Ph.D. in biochemistry from the University of North Carolina. Afterwards, he conducted postdoctoral research at the Wellcome Research Laboratories. Alan served on the faculty at Rockefeller University before joining Parke Davis Pharmaceutical Research in 1990, where he remained until 2001 when he accepted a position at the University of Michigan. He transitioned to his current positions in 2015. Alan has received numerous awards and honors, including the Rosalyn Yalow Research and Development Award from the American Diabetes Association; the Hirschl Award from Hirschl Trust; the John Jacob Abel, Goodman and Gilman, and Pharmacia-ASPET Awards from the American Society of Pharmacology and Experimental Therapeutics, and he was named a Fellow of the Society in 2022. In addition, Alan is an elected Fellow of the American Association for the Advancement of Science, an elected Member of the American Society of Clinical Investigation, and an elected Member of the National Academy of Medicine. In this interview, Alan shares more about his life and science.
People Behind the Science Podcast Show Notes
Life Outside of Science (3:21)
When he’s not working, Alan enjoys exercise and physical activity, including tennis and occasionally basketball. He also likes to read fiction and non-fiction, spend time with friends and family, and experiment with cooking Mediterranean cuisine.
The Scientific Side (8:23)
Alan studies how cells that are involved in metabolism decide to take up and store energy, burn energy, or release energy for other cells to use in response to hormones, nutritional cues, and metabolic stress. He is particularly interested in studying cells in liver and fat tissues and better understanding the pathways involved in controlling the metabolic activities of these cells.
A Dose of Motivation (9:38)
“It’s not your duty to finish the work, but neither are you free to neglect it.”
What Got You Hooked on Science? (14:00)
Science was interesting to Alan throughout high school and college, but he was slow to decide he wanted to pursue a career in research. Alan majored in Zoology in college, and he was particularly interested in signaling pathways and metabolism. However, he didn’t think he was smart or creative enough to become a scientist. He went to graduate school because it seemed like a natural next step, and he figured he could check it out and maybe find something else that might work out for a career. During graduate school and his postdoctoral fellowship, Alan began to discover that he could do science. By the middle of his postdoc, Alan was excited and energized by the questions he was answering, and it became clear to him that this was what he wanted to do for his career. He started his first faculty position at Rockefeller University in New York, and things were going pretty well for him. Another twist in Alan’s career path came in 1990 when his postdoctoral mentor moved to Michigan to become the president of research and development at a pharmaceutical company. When this mentor asked Alan if he would join him, initially Alan thought it wouldn’t be a good fit. After visiting the company, Alan decided that working in drug discovery could be an interesting opportunity after all. He made the jump to industry and worked there for about ten years before returning to academia.
The Low Points: Failures and Challenges (24:56)
In the 1990s, one focus in the field was trying to understand how signaling proteins that control metabolism are restricted in space within cells and how hormones accomplish specificity in their signals within cells. Alan’s lab used a screening procedure to find proteins that bound to their two proteins of interest. This approach was really useful, and they published their new findings in great papers. However, there were a few situations where they thought they had a really fascinating finding, but it turned out to be not very cool. For example, a postdoc in the lab worked on a project to identify a protein that was interacting with one of their proteins of interest. They got a positive result when they ran a screen for binding, and the result looked really exciting initially. Based on these promising results, they spent a year trying to figure out the nature and significance of this interaction, and what it could mean in the context of cell biology. Alan and this postdoc came up with grand ideas about a new pathway and a new way of controlling metabolism. While the interaction was real, ultimately, they had to admit that it wasn’t really interesting and didn’t really impact the biology of the cell in a meaningful way.
A Shining Success! (27:09)
Alan and his lab members have been really interested in the role of inflammation in controlling the action of insulin in obesity. Individuals who are obese commonly become resistant to insulin, and Alan thought inflammation may be a key part of the mechanism for the development of insulin resistance. In studying the inflammation pathways, they discovered a molecule that was important for translating inflammation to insulin resistance, and they thought this molecule was the link between obesity and insulin resistance. Additional experiments confirmed their findings. They also identified a drug that could inhibit the molecule that was already approved for use to treat asthma. The drug was effective in animal models and it underwent a clinical trial, which showed that it could help control blood sugar in humans. Alan thought they had the whole story, but there were some nagging details about the pathway that still didn’t make sense. After presenting their work at a scientific conference, someone from the audience approached Alan during the coffee break with some questions. This conversation gave Alan the nudge he needed to bring the project back to the lab and have the group do a deep dive on what exactly was happening. Finally, they were able to fill in the missing pieces, and the story they uncovered about the mechanism was even more interesting than the initial story they put together. Seeing the process all the way through from the initial discovery of the molecule, unraveling the mechanism, and running a clinical trial for a drug treatment over a period of about ten years was really rewarding.
Book Recommendations (4:34)
Thinking, Fast and Slow by Daniel Kahneman, The Inner Game of Tennis by W. Timothy Gallwey, Between Parent and Child by Dr. Haim G. Ginott
Most Treasured Travel (31:20)
In the early 2,000s, Alan visited the city of Naples and the island of Capri in Italy for scientific meetings. During the trip, he enjoyed a luncheon overlooking the sea in the village of Positano, a tour of Pompeii, exploring the grottos of Capri, and boating in the Bay of Naples in addition to the wonderful scientific discussions at the meetings. These kinds of trips are best when you can explore the destination with an insider who can show you all of the cool local places.
Quirky Traditions and Funny Memories (33:30)
Over the course of his career, Alan has had opportunities to meet many wonderful scientists, many of whom have become great friends. These people are zealots about their science, but they are also active, interesting people who do lots of different things. When he and his colleagues get together at conferences, they enjoy the scientific sessions, but they also hike, play tennis, and engage in some good natured teasing. In his current lab, Alan has a weekly journal club where the students and postdocs present a paper for the group to discuss. At the beginning of each session, the presenter has to spend about five minutes talking about scientific history. This has helped raise awareness in the group of some of the important people in their field, the personalities of famous scientists, the circumstances surrounding important discoveries or the development of a key lab instrument, and the role of chance and serendipity in scientific discoveries. The lab has really enjoyed this tradition.
Advice For Us All (38:05)
Find your own way. Not everyone approaches work and science in the same way, and there isn’t one single best approach. Find the questions that you are most excited about. If you aren’t excited about the questions, then they are either not the right questions for you, or this may not be the right career for you.
Guest Bio
Alan is a cell biologist who researches the hormone insulin and how it relates to obesity, diabetes and other metabolic disorders. He and his lab members are investigating how metabolically active cells control energy storage and utilization in response to hormones and nutrients in health and disease. Diabetes and obesity arise from dysregulation of energy metabolism. In order to make progress towards new treatments, we require a better understanding of the underlying molecular mechanisms. To this end, the Saltiel lab investigates the molecular events involved in the regulation of nutrient uptake and storage by insulin, as well as regulation of mobilization and utilization by catecholamines and glucagon. The lab seeks to understand how energy metabolism is controlled in fat and liver cells, and how these cells talk to each other, with special attention to mechanisms underlying the specificity of the actions of hormones, and the inflammatory links between obesity and diabetes. Alan holds 19 patents, has published more than 300 original papers, and has successfully developed drugs for diabetes and cancer.
Support for this episode of People Behind the Science was provided by Innovative Research, Inc.