Stony Brook’s Seeliger, Foda team up in diabetes discovery

Stony Brook’s Seeliger, Foda team up in diabetes discovery

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Early in his career, Zach Foda, who graduated from Ward Melville High School in 2005, has done something his father, Hussein Foda, an award-winning pulmonologist and medical researcher, hasn’t accomplished in a medical and research career that spans over three decades.

An M.D.-Ph.D. candidate at Stony Brook, the younger Foda recently participated in a research project on diabetes that was published in the prestigious journal Nature. The study, led by David Liu, a Harvard professor of chemistry and chemical biology, found a new possible treatment approach for diabetes, inhibiting something called the insulin-degrading enzyme.

“The Journal Nature is one of the very highest-impact journals in the country and actually in the world,” said the pulmonologist father, who is a professor of medicine in the pulmonology critical care division at Stony Brook. Everything after this, he laughed, may be “downhill.” As a member of Markus Seeliger’s lab in the Department of Pharmacology, Zach Foda helped determine the three-dimensional structure of the inhibitor compound and showed how it was bound to the insulin-degrading enzyme.

Over 20 million people in the United States live with type II diabetes, a problem in which the body can’t make enough of the hormone insulin. The IDE removes insulin from the blood. People with diabetes typically inject insulin, take medicine to increase their sensitivity to the hormone or take other drugs to increase the insulin their bodies produce. Inhibiting the effect of this enzyme may enable insulin to remain active in the blood for a longer time.

Testing their compound in mice, Liu and his Harvard colleagues showed that the inhibitor increased insulin levels, which in turn lowered blood sugar. While this study is encouraging, scientists caution it could be some time before this approach goes through all of the screening steps to become an approved treatment for diabetes.

Seeliger and Foda became involved in this collaboration at the request of Liu. An expert in determining the structure of molecules, Seeliger studies the structure of inhibitors of enzymes called protein kinases, some of which are involved in cancer.

When Liu reached out to Seeliger in the fall of 2011, the Stony Brook researcher didn’t hesitate to join the latest collaboration. Liu is “a total rock star in the field,” Seeliger offered. “I was delighted when he contacted me out of the blue initially. It was a no-brainer to say, ‘Sure, we’d be interested.’” Liu praised his Stony Brook collaborator. Seeliger is “a highly talented, dedicated and scholarly biochemist and structural biologist,” Liu offered in an email. “He is a superb collaborator and an asset to our community.”

While Seeliger contributed an important element to the diabetes study, he focuses more of his work on other areas, including studying the structural nature of kinases and the drugs used to affect them. Kinases are “important drug targets,” Seeliger said.

“There are a lot of potential compounds out there that could become drugs for kinases, but most of them don’t work well enough. We want to help understand why they don’t work.”

Kinases are signaling molecules inside the cell. If they send an incorrect signal, a cell could die or develop cancer, Seeliger explained. The problem in targeting these kinases is that there are many similar signaling molecules and it’s “difficult to turn off one without turning another one off. We need a high specificity of kinase inhibitors.”

The “Holy Grail” for Seeliger in his research would be to find out how a drug binds to a receptor, and not just what the final configuration of the drug and the receptor are. Seeliger, who considers himself a visual person, said he is humbled by people who bake professionally. Being able to manipulate yeast, flour and other ingredients to create a moist and spongy bread is something that “impresses me.”

Seeliger, who lives in Stony Brook, is married to Jessica Seeliger, an assistant professor who is also in the pharmacology department at Stony Brook. The couple enjoy going to the beach and visiting Stony Brook Village. Seeliger is a scuba diver who has explored the waters around Long Island.

Seeliger credits Foda with doing much of the hands-on and computational work on the structural part of the diabetes study.

Foda recently married equine veterinarian Kiara Barr and is going back and forth between Long Island and Westchester, where his wife will work with and show horses until she moves to the University of Pennsylvania next year.

The elder Foda said he is “very excited” for his son’s early success and, as someone who chose to combine medicine and research, is also pleased with his son’s career choice. “I’m very proud of him.”