My work revolves around signal transduction, particularly as it pertains to the hormone insulin and its ability to promote the uptake and storage of carbohydrates and lipids. As an undergraduate student I became interested in hormones, how they do what they do. This is an important topic to a teenager.

“…[MAP kinase] didn’t tell us anything about diabetes, but the molecule became a template for the discovery of drugs for cancer, inflammation, and other proliferative diseases.”

We started working on the MAP kinase pathway over 17 years ago. I worked in signal transduction and insulin, and MAP kinase had just been discovered by Tom Sturgill as a potentially important intermediate in insulin action. My lab started looking at the enzyme, to figure out what activated it and how it was regulated. We found that many extracellular signals (like Nerve Growth Factor) could turn it on, and I suspected that it might not be that important in insulin’s actions, but perhaps could play a crucial role in growth control—maybe even be important in cancer. After I moved to Parke Davis, I realized we had an opportunity to look for small molecules that would block the activation of the upstream activator MEK, since such molecules would give us a handle on the role of MAP kinase in all kinds of biological processes. We searched for molecules and found a few, including one really good one that was very specific but did not have great pharmaceutical properties. In other words, it didn’t look like much of a drug candidate, but did look like a great research tool. We then examined its effects on processes that we thought might or might not involve MAP kinase. The compound blocked the growth and differentiation of some cells, but not others, and had no impact whatsoever on the metabolic effects of insulin. So in a sense, it didn’t tell us anything about diabetes, but the molecule became a template for the discovery of drugs for cancer, inflammation, and other proliferative diseases.

After we published the first few papers on the compound, I received virtually hundreds of requests for it. I made the compound available to everyone who wanted it, and it quickly became an important research tool. Soon afterward I kind of lost interest in the MAP kinase field, and focused most of my lab back on important signaling pathways in insulin action. We’re still pushing forward trying to investigate the pathways that control how insulin increases the uptake and storage of sugar in fat and muscle cells.

Well, when I first started my career in signal transduction, it wasn’t referred to as signal transduction. Most of us started working on receptor biology, trying to figure out how receptors were coupled to intracellular changes. Since then there has been an explosion in the field of signal transduction, which now encompasses how processes as diverse as secretion, gene expression, vesicle trafficking, metabolism, etc. are regulated between cells. My lab now mainly focuses on the intersection of signal transduction and vesicle trafficking.

Playing point guard for the New York Knicks. As a matter of fact, it’s kind of surprising that I’m not doing it right now; it would only occupy half a year anyway, because the season just lasts from October to June, leaving me plenty of time for science. I know there are some people who would be concerned about my age, not to mention speed, strength, agility, shooting ability, and so on, but these are minor issues. Hopefully someone from the Knicks organization will read this interview and give me a call.

By that time I suppose my hoops career will be slowing down, so I’ll have to be a bit more focused on the lab. Right now many of us are trying to figure out the key determinants of specificity of signaling, thinking a great deal about time and space in cells. I suppose we’ll soon have identified most of the scaffolding proteins and interaction domains, and will be thinking more about signaling in a physiological setting, with the goal of using more computer modeling to figure out where the hubs and nodes are in pathways, and how crosstalk modulates hormone sensitivity.

Alan R. Saltiel, Ph.D.
University of Michigan Life Sciences Institute
Ann Arbor, MI, USA