Department of Chemistry

School of Natural Sciences and Mathematics

Superman may have X-ray vision, but can he diagnose what's physically wrong with you in a single glance?

Coming up with the proper mix of compounds that will allow physicians to see what's going on inside their patients is no easy task. Just ask A. Dean Sherry, Ph.D., professor of chemistry at The University of Texas at Dallas (UTD), who develops and tests contrast agents used in magnetic resonance imaging (MRI).

With a simple injection, Sherry said scientists soon will be able to look at tissues and cells in a way doctors never have before and obtain a world of information without invasive techniques.

The imaging agent will leave no trace and produce no after-effects, having successfully delivered internal images, such as a pH map of your body or perhaps a map measuring individual oxidative stress.

Sherry, who holds the Cecil H. and Ida Green Distinguished Chair in Systems Biology #1, and has a joint appointment at UT Southwestern Medical School as a professor of radiology, has more than 30 years of experience and is considered a leader in the field. He recently won a grant for $180,000 from the Houston-based Welch Foundation for his research on “Lanthanide-Based CEST Agents for Metabolic Imaging.”

“Imaging agents are used clinically so that when people get an MRI now, they may actually inject you with something called gadolinium. Gadolinium is really an irradiating substance that I’ve studied for years,” Sherry said.

Gadolinium is FDA-approved, clear like water and not radioactive. Once injected, gadolinium accumulates in the abnormal tissue and causes them to become very bright or enhanced on the MRI.

“There’s a pretty big market for drugs like this,” he said.

Sherry founded a side enterprise, Macrocyclics, a UTD spinoff that stores and produces chemical compounds used in pharmaceutical and academic research.

“Our lab and other labs have continued to work on new agents. And we have some totally new products now called responsive agents. And these we may someday put into humans and they will tell us something about metabolism,” Sherry said.

He gave an example.

“If your liver is overproducing glucose, we’d like to be able to put an imaging agent in there to quantify that just by imaging.

“If you are diabetic, what’s the proper drug to give you to slow down the process? These imaging agents are becoming more versatile and more informative than the first generation,” he said.

Kidneys

Magnetic resonance contrast agents from the Sherry lab show a typical pH gradient in the functioning kidney of a live mouse.

In his work, Sherry says he enjoys the best of both worlds. On the chemistry side, he is designing and researching drugs and on the radiology side he is testing them and seeing what the drugs can reveal in animals.

“It's really fun because the design of new agents is just basic chemistry, and that's what we do here in the labs at UTD. But the advantage I enjoy is that we can then go to the medical school and use a variety of medical imaging devices to test our compounds in animals and just see what we can learn about the whole animal that's useful," Sherry said.

In the beginning…

Hired as an inorganic chemist at UTD, Sherry quickly developed an interest in biochemistry.

“I began teaching biochemistry. At first, I was team-teaching with Mike Patrick, one of the early Cell and Molecular Biology faculty members, and I just grew to love the subject. It’s all about the chemistry of life – basic metabolism in your cells is just small-molecule chemistry," Sherry said.

During those early years, Sherry said his exposure to metabolism had a big impact on his research.

"It provided me some insights that most other inorganic chemists working in this field do not enjoy,” he said.

Sherry said that the interdisciplinary interaction makes UTD special.

“There aren’t many labs – in the world, really– that do what we do.

“Thanks to my background, it kind of makes me unique because I’m a chemist by training but yet I understand insights into the human body and metabolism as well. I enjoy it because I feel that my research can make an impact in society," he said.

Eye-opening discovery

About four years ago, one of Sherry’s graduate students made a very important discovery.

“A student brought an nuclear magnetic resonance spectrum of a molecule one day that really opened my eyes. I noticed this highly shifted water peak and that basically led to a whole new way of thinking about contrast agents.

“You never know when a student or post doc is going to come in with a spectrum that you can’t explain. It’s something unusual. But the trick of science is to recognize it. To recognize that this is unusual and that there’s something important here.

“So the challenge really is to maintain an open, inquisitive mind and expect the unexpected. That’s how you make great discoveries,” Sherry said.

As a result, Sherry and his lab team built up the body of knowledge on imaging agents and expanded the field's vocabulary in the same breath.

“This discovery told me that there was another way to produce contrast in an image besides gadolinium. And it’s called CEST – chemical exchange saturation transfer – and the term that we introduced – someone else introduced the term CEST in another application – was the idea of using paramagnetic complexes as CEST agents so we came up with this word, PARACEST. A beautiful word, and it’s something that we invented.

“Now my whole lab is working on nothing but PARACEST agents.

"We have learned that if you are clever and alter the chemistry of these molecules slightly, you can develop agents for targeting specific metabolic events, such as glucose production in the liver. One can also use PARACEST agents to measure tissue pH levels, so we turned that into an imaging method to find out what parts of your body are more acidic than they should be.  I think that is going to be important, particularly in cancer research, because tumors tend to get acidic,” Sherry said.

New imaging agents

Currently, Sherry's lab is developing an agent to help identify and perhaps treat something that’s been in the news of late: oxidative stress.

Redox is a shortened word for oxidation/reduction. We live in an oxygen-rich environment and all of our metabolic processes are oxidative where one ultimately converts oxygen from the air into water, he said.

“In the process of doing this, through metabolism, you make a bunch of reducing implements. So every time that happens in a biological reaction, if there is an oxidation occurring then there also is a reduction occurring. So electrons get transferred from one thing to another. And the balance of this is very important.

"Are you more highly oxidized or are you more highly reduced?” he asked.

The answer is coming soon.

  • Updated: July 24, 2013