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The Hunt for New Drugs to Treat Infectious Diseases

By Jen A. Miller

TomshoFor JOHN W. TOMSHO PhC’98, PhD, assistant professor of chemistry and biochemistry, taking a position at USciences, wasn’t exactly a new adventure. It was more like a homecoming since he earned his undergraduate degree here.

As an undergraduate student, “it’s a huge [advantage to have] access to your professors and do state-of-theart, cutting-edge research,” he said. “It’s amazing and almost unheard of anywhere else.”

The mission of his lab’s research, which has been sponsored by the W. W. Smith Charitable Trust and the Milton Lev Memorial Faculty Research Fund, is to discover new drugs. “We’re doing research specifically looking for drugs that we can use to treat infectious diseases,” he said. “Right now, we are focusing on new antibiotics and new antivirals.” Some key targets: HIV, malaria, influenza, and tuberculosis.

In one prong of his lab’s research, he’s incorporating boronic acids into small molecule drug design. Boron hasn’t typically been part of the equation in drug development, but Dr. Tomsho sees potential there.

“I’m making them play with the body a little bit better so these molecules get to where they need to go,” he said. “Once they’re there, they have some unique chemistry that they can do.”

By preparing analogs of natural substrates, existing drugs, or natural products that have antibacterial or antiviral activities, he hopes to improve on them and add a new tool to the medicinal chemist’s toolbox in the process.

Another area of research is developing an in vivo system for the discovery of inhibitors of protein-protein interactions, specifically an interaction that plays a key role in influenza.

“We think if we can disrupt this protein-protein interaction, we can make influenza less virulent,” he said. “You won’t get as sick for as long, and you won’t be able to spread it as easily to other people.”

Influenza only has 10 genes, and current therapies target two of them— and the influenza viruses currently circulating are starting to develop resistance to these therapies. The target of his therapy is a “gene relatively left alone because it’s very inaccessible for traditional medicinal chemistry approaches,” he said.

quoteThe third prong of his lab’s research focuses on Lariatin A, a small peptide natural product of a soil bacterium that shows activity against tuberculosis. His lab is engineering E. coli to produce this synthetically inaccessible natural product with the hope that it can be readily prepared in the laboratory.

“We’re taking the natural machinery and subverting it to make it do what we want it to do,” he said. “If this is successful, these peptides are very resistant to heat, they are very stable, and they do have a lot of drug-like potential that we could use down the road as we go forward.”

Dr. Tomsho earned his undergraduate degree in pharmaceutical chemistry at USciences and came back because “I was looking for an institution that would allow me to do a mix of research and teaching,” he said. His wife (LYNN PELLEGRIN TOMSHO BC’98) and brother (RICHARD TOMSHO MPT’00) earned degrees here as well.

He knew how crucial his undergraduate training was to his professional development and wanted to be in a place that offered that opportunity to current students. “This is a really interesting and unique place. You have the ability to do undergraduate research to a high level, which is really hard to get,” he said.

Read more about the exciting research conducted at USciences:

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