April 03, 2013

Carrie Bebermeyer

Saint Louis University Professors Receive Honors for Their Contributions to Science

Awardees Made Their Marks with Fruitflies, Catalysts and Cholesterol

Three Saint Louis University scientists -- Dale Dorsett, Ph.D., Grigoriy Yablonsky, Ph.D. and Angel Baldan, Ph.D., will be honored by the Academy of Science-St. Louis at the organization's 19th annual awards dinner, held to celebrate the top scientists and engineers in the St. Louis region. The April 24 event is hosted by the 157-year-old academy as a part of its mission to promote the advancement and understanding of science and technology in the region. This marks the first time SLU has had three awardees in the same year.

Dale Dorsett, Ph.D.

Dale Dorsett, Ph.D., professor of biochemistry and molecular biology, will receive the Fellows Award in recognition of outstanding achievement in science. Because of his pioneering work over the last 30 years, we better understand a fundamental molecular mechanism by which gene expression is regulated during development.

Dorsett has spent much of his career studying cohesin, a protein complex that ensures that new daughter cells have the correct number of chromosomes when a cell divides, and which also influences gene expression. In fact, he’s been called “The Godfather of Cohesinopathies.”

In the course of his study, Dorsett’s work shed particular light on Cornelia de Lange syndrome, an inherited genetic disorder that is characterized by distinctive facial appearance, low birth weight, slow growth, small stature and small head size. Those who have the disorder also frequently experience medical issues like gastro-esophageal reflux disease, heart defects, seizures and vision and hearing problems.

Dorsett found that his work took him beyond the laboratory and out into the community when he was asked to talk with parents of children diagnosed with Cornelia de Lange Syndrome (CdLS). He served on the board of directors for the CdLS foundation for six years, and now serves on the organization’s research committee. And, he’s participated in a large symposium held every two years for the families of children recently diagnosed with the disorder.

One of the parents came up to me afterwards and said, ‘I think I’m going to go home and throw away my fly swatter.’

--Dale Dorsett, Ph.D.

Though most of Dorsett’s research has been done using the fruit fly Drosophila melanogaster, his discoveries have a significant impact for our understanding of human gene regulation and provide critical insight into the cause and potential treatment for a class of human inherited disease.

The value of lessons learned from the fruit fly was not lost on some of the parents Dorsett spoke with at one of the symposiums.

“I was invited to talk one year, because, at the time, I was one of the few people who even knew about cohesin,” Dorsett said. “So, I gave a little talk, and explained how it was discovered in fruit flies and how we are studying its function. I explained how studying flies shed light on human genetics. A fly is basically a stripped down human being, genetically speaking.

“One of the parents came up to me afterwards and said, ‘I think I’m going to go home and throw away my fly swatter.’”

Using Dorsett’s Drosophila model, drugs with the potential to treat Cornelia de Lange syndrome in humans are being rapidly and inexpensively tested in the fly to discover if any may be good candidates for a clinical trial.

In his latest finding, Dorsett’s research suggests that the cohesin protein complex controls the transcription of most genes in our cells, a much broader role than scientists previously believed the protein played.

Grigoriy Yablonsky, Ph.D.

Grigoriy Yablonsky, Ph.D., associate research professor of chemistry, will receive the James B. Eads Award for outstanding achievement in technology. Yablonsky is a world-recognized expert in the area of chemical kinetics, catalysis and chemical engineering with achievements in both academia and industry.

Yablonsky loves his work because it stands at the crossroad of several fields.

“It’s chemistry, it’s mathematics, it’s chemical engineering, it’s physics.

“Chemistry is about the transformation of molecules,” Yablonsky said. “The most amazing thing happens in the presence of a catalyst. Catalysts are mysterious substances. Just a small amount of a catalyst accelerates reactions.”

And, the catalyst is a big deal when it comes to industry. Catalysis drives 90 percent of all industry questions related to chemistry, Yablonsky says.

“This is especially true when it comes to sustainable energy. In order to find alternative sources of energy, we need a catalyst. So catalysts are answers to today’s biggest industrial questions.

“My colleagues and I work with industry. We are working on problems of complete and partial oxidation. It may accelerate progress in processes of combustion or production of plastics, for example.

In fact, catalysis is a driving force of sustainable development. It is also an extremely interesting academic question.”

’To stay in place, you have to run.’ It means that to keep up, we must invent something new, we must be creative for commercialization. 

-- Grigoriy Yablonsky, Ph.D.,

Yablonsky’s theory of complex steady-state and non-steady state catalytic reactions is used by research teams around the globe. Bridging chemical kinetics and mathematics, Yablonsky developed a new paradigm for decoding certain types of catalytic reactions based on rigorous relationships between observed reaction behavior and complex reaction mechanism.

He also created a theory for the advanced worldwide experimental technique (Temporal Analysis of Products-TAP) developed in St. Louis by John T. Gleaves, a chemical engineer at Washington University. This technique is used to characterize the kinetics and chemical conversions of heterogeneous catalysts.

Emphasizing the importance of practical innovation, Yablonsky paraphrases the Red Queen in Lewis Carroll's Through the Looking-Glass. “’To stay in place, you have to run.’ It means that to keep up, we must invent something new, we must be creative for commercialization. We must somehow find a catalyst, characterize it, produce it, and it must be stable.

“It’s not only science, but it’s art.”

Born in Russia, Yablonsky worked at the Russian Institute of Catalysis before spending the last 17 years in St. Louis. Besides his academic work, he’s written autobiographical stories in Russian – funny stories, he says.

The humor carries over to his scientific writing. The first line of his textbook is a joke.

“Chemistry is a complex science, especially for chemists,” he writes in Kinetics of Chemical Reactions, which he co-authored.

“I like jokes for scientists. People should know: science is not boring.”

His advice for future scientists? “I think you have to find one, just one, interesting problem to solve.”

And, though Yablonsky may be a jack-of-all-trades, from literature to mathematics, he knows what makes a person a scientist at heart.

“Who is a scientist? A person who is thinking about science before sleep. If you are thinking about other things, you may be a banker, a politician or a writer. But if you’re thinking about an interesting scientific problem, you may be a scientist.”

Angel Baldan, Ph.D.

Angel Baldan, Ph.D., assistant professor of biochemistry and molecular biology, will receive the Innovation Award for a young scientist who has demonstrated exceptional potential for future accomplishments. His findings suggest potential new approaches to manage patients at risk for cardiovascular disease; new insight into the statin therapy; and improved effectiveness and safety of cholesterol-lowering medication.

Creativity, Baldan says, is about bringing together previously disconnected concepts. It’s also about thinking differently about things we already know so we can make new connections.

“So, I have had many ideas. Most are wrong or crazy. But some pan out,” Baldan said. “For every hypothesis that works, there are several that don’t.

“As someone once said, ‘Success is going from failure to failure with great enthusiasm.’”

Baldan’s work focuses on the microRNA miR-33. In 2010, he found that the gene plays a key role in regulating cholesterol metabolism by modulating the levels of HDL (the “good cholesterol”). And, in 2012, he found that that the gene accomplishes this by also regulating bile metabolism.

Now, he’s trying to untie another knot in the cholesterol metabolism conundrum. Because, as most scientists will tell you, for each answer you find, you’re likely to receive a new batch of questions.

“We’ve seen that this microRNA controls expression of sterol transporters,” Baldan said. “There’s this model in the field that says that if one accelerates the mobilization of cholesterol via HDL and bile secretion, excess cholesterol could be removed from the body. In theory, that should reduce cardiovascular disease by reducing the burden of cholesterol in the arteries.

If you work on cool projects, you'll have competition.

--Angel Baldan, Ph.D.

"Then, we’ve shown that when we lower the expression of miR-33, both HDL levels in blood and the loss of sterols through the bile increase. The next logical step was to see if this treatment prevents cardiovascular disease in a mouse model of cardiovascular disease. The answer? No, it doesn’t."

“Everything pointed this way. But we didn’t see what we expected. Now, we’re trying to understand why the treatment failed to prevent atherosclerosis. Many questions remain to be answered.

“We hypothesize that there are yet to be discovered homeostatic pathways that compensate for the reduction in miR-33, thus preventing a sustained, effective outcome of the treatment.”

As he turns his attention to solving this piece of the puzzle, Baldan is aware that his findings are taking him down roads being traveled by other labs. Harvard and NYU are studying similar questions, giving the search for answers to these questions a sense of urgency and professional competition. Baldan interprets the interest in the miR-33 area of study as a sign that they are on to something with big potential.

“If you work on cool projects, you’ll have competition,” Baldan said.

Luckily, Baldan has a proven track record in innovative approaches to scientific questions that will serve him well as he tackles this next question.

Dinner tickets and tributes for the April 24 event are available through the Academy of Science-St. Louis website www.academyofsciencestl.org or by contacting Lynn Cook at 314-289-1402.

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