Russell Debose-Boyd

This is just the tip of the iceberg, says Deisseroth, who has distributed optogenetic technology, free of charge, to more than 350 labs around the world. He is pressing ahead to refine new bio-optical switches that can inhibit as well as excite neurons and to apply the technology to better understand neural circuits in health and disease. Meanwhile, Deisseroth is board-certified by the American Board of Psychiatry and Neurology and continues to care for patients.

Russell DeBose-Boyd's story is about finding a way around the statin stalemate. Twenty million Americans take a statin every day to reduce their levels of “bad” cholesterol—low density lipoproteins, or LDLs. Statins dramatically cut LDL levels in some patients, says DeBose-Boyd, who is at the University of Texas (UT) Southwestern Medical Center, in Dallas. But the body responds to the plummeting cholesterol levels with a feedback system that tells the cells to compensate by making more cholesterol.

To understand the statin impasse, DeBose-Boyd studies HMG-CoA reductase, an enzyme that sets the rate of cholesterol synthesis. Statins block the enzyme but, paradoxically, also seem to drive up reductase levels, he says, by slowing their natural degradation. Blocked by statins, the accumulating enzyme convinces the cell's sensing system that cholesterol levels are crashing, and the cells respond by attempting to rev up synthesis. DeBose-Boyd hopes to make statins work better, or find entirely new drugs that control reductases better and make statins obsolete.

DeBose-Boyd's other story is how he found his way into science. He comes from a tiny farming community in rural Oklahoma and began his studies at Southeastern Oklahoma State University, in Durant, an institution not noted for producing protein biochemists. He followed his interests in biology to the University of Oklahoma Health Sciences Center, in Oklahoma City, where his Ph.D. mentor, glycoprotein biochemist Richard Cummings, recognized his talent. Cummings enthusiastically promoted DeBose-Boyd as a postdoctoral fellow candidate to the UT Southwestern Medical Center research duo of Michael Brown and Joseph Goldstein, who won the 1985 Nobel Prize in Physiology or Medicine for their discovery of the regulation of cholesterol levels by statins. That discovery set off the statin revolution but the exact mechanism and the paradoxical self-limit of statin efficacy stymied their lab for a decade.

Then DeBose-Boyd arrived and turned his attention to the interplay between statins and reductase. He worked his way around a major technical hurdle by discovering a regulated binding partner of reductase that allowed overexpression of the enzyme in sufficient quantities while preserving its natural degradation. This discovery permitted him to map out interactions between reductase and its binding partner and focus on reactions that lead to the enzyme's degradation. It soon became clear to Brown and Goldstein that DeBose-Boyd was someone to keep around UT Southwestern and they engineered his move to independent faculty status.

Photo: Courtesy of UT Southwestern

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