The search for the right recipe to help people feel better

A team of chemists - students and research fellows from the United States, Australia, Africa, China, India, Greece, and France - work side-by-side in a School of Pharmacy laboratory, manipulating and designing molecules. They are learning how drugs are developed from a world leader in drug discovery, Alexandros Makriyannis, a professor of medicinal chemistry and molecular and cell biology in the center for drug discovery at UConn.

Alexandros Makriyannis, a professor of medicinal chemistry and molecular and cell biology in the School of Pharmacy, works on discovering therapeutic drugs.

Makriyannis is intent on understanding the mechanisms by which therapeutic drugs produce their effects. He is working to synthesize new chemicals that will aid in the fight against drug addiction, to develop better pharmaceuticals to combat disease and to ease the pain caused by long-term conditions such as arthritis.

Makriyannis is one of the University's most successful researchers in obtaining research funding. Major funding for his research comes from the National Institutes of Health, with additional grants from the state of Connecticut and the pharmaceutical industry.

He currently directs a research group of 35 assistant professors, visiting scholars, postdoctoral fellows, and graduate students. He also has welcomed high school students into his labs.

"One of the attractive features of being a scientist is that science eliminates lots of barriers between people - barriers of country, religion and age - because everyone is excited about what they're doing and the potential for making discoveries," says Makriyannis.

It is the science that drives him, the challenge of learning and discovering something new. "You want to direct your efforts to something that will help people," he says. "I like to conduct research which has an anthropogenic content, where you can relate it to human beings ultimately. We do work with concepts, which are sometimes quite intricate; however, we want to ultimately apply our results to human beings."

At the heart of Makriyannis' research is an approach that involves designing new molecules that take on specialized biochemical properties. He has used various approaches to design the molecules, including computers and other experimental methods.

"We make them or 'cook' them," he says, "and the molecules we make have different potential uses, either as research tools or as therapeutic agents."

He says the challenge is to design a molecule that will attach to a human cell so that it turns certain cellular switches on or off, helping to improve a patient's health and well-being.

In collaborative research with the Brookhaven National Laboratories in New York, Makriyannis has developed a new molecule that acts as an imaging agent to allow a scanner to detect diseased tissue. He says this could have significant diagnostic capabilities involving early detection of some degenerative diseases, such as Huntington's chorea and Alzheimer's disease, long before there is massive degeneration in the patient.

The pioneering research is one of three major advances in Makriyannis' lab during the past several years in the field of molecular research with a class of molecules found in the hemp plant that interact with a biochemical system known as cannabinoids.

His work with cannabinoids research has also led to a new approach in treating pain caused by degenerating nerves that could provide help for individuals suffering pain caused by diabetes, shingles, or cancer.

This is a computerized, three-dimensional view of a new molecule that was developed in the UConn laboratory of Alexandros Makriyannis.

In another project, Makriyannis discovered a protein transporter, which has been shown to have a major role in regulating a number of body functions and activities. This is being used in the development of medications for the treatment of disease conditions such as multiple sclerosis and some complications in the body's circulatory system.

Since 1974, when he arrived in Storrs as an assistant professor of medicinal chemistry, Makriyannis has distinguished himself as a scientist, scholar, teacher and mentor. In 2002, he was the recipient of the Board of Trustees Distinguished Professor Award, the highest academic title for UConn faculty members.

His work also has been recognized by his peers. Last November he received the prestigious 2002 Research Achievement Award in Drug Design and Discovery from the American Association of Pharmaceutical Scientists, a group that serves as an educational, scientific and scholarly body for more than 11,000 pharmaceutical scientists.

During his career, Makriyannis has served as advisor and mentor to hundreds of students at the postdoctoral, graduate, and undergraduate levels. Many of his former students now hold top industry posts.

Stephen Fesik '81 Ph.D. among the first graduate students Makriyannis mentored, has distinguished himself as a scientist and is currently divisional vice president of cancer research at Chicago-based Abbott Laboratories. Bonds between the two remain strong: Fesik has returned to UConn to give talks, and his former professor has met with Abbott's scientists.

"Alex has a style that makes you think for yourself and then follow up. Through his guidance, I learned to think about science," Fesik says.
-- Claudia G. Chamberlain