A passion for precision
The Department of Chemistry seeks new approaches to diagnosing and treating medical conditions
Researchers in the Department of Chemistry are searching for better methods to diagnose liver cancer and ways to treat diabetes and alcohol addiction. Two recent grants have helped to elevate the medical research being done within the department.
Calorimeter offers extreme accuracy
When it comes to diagnosing liver cancer and developing medications to fight HIV, being precise is key. A new device in the Center for Science and Technology measures minuscule amounts of heat generated or absorbed when two molecules interact, providing extreme accuracy. According to Ivan V. Korendovych, associate professor of chemistry, this piece of equipment could lead to new medications to prevent HIV, the virus that causes AIDS, and better liver imaging, which could eventually make it easier to diagnose liver cancer.
The isothermal titration calorimeter was purchased with a $100,000 grant from the National Institutes of Health (NIH) plus $50,000 in matching funds from the College of Arts and Sciences and the office of the vice president for research.
“This is a very fundamental kind of instrument that strengthens our position as a primary R1 (research) institution in the area,” Korendovych says. Syracuse University is one of only 131 universities in the country to hold an R1 distinction from the Carnegie Classification of Institutions of Higher Education. The classification is given to universities that devote a substantial amount of funds and resources to research, and those with a large number of faculty and students conducting research.
The calorimeter can precisely measure minuscule amounts of heat, which is produced or consumed in all chemical reactions. “It allows us to quantitatively measure interactions between molecules,” Korendovych says. “Because every interaction generates heat, it can be used for everything. (Potential uses) go from theoretical to very practical things.”
One application is testing protein-drug interactions. “A medication works because there is an interaction. It inhibits some biological pathway,” he says. Researchers measure the heat generated when two materials like a drug and a protein in human cells interact. The amount of heat released and measured by the calorimeter indicates the strength of the interaction and if the medication will work.
“We have some new ideas and approaches for medications preventing HIV that are in the works,” he says. “Testing the strength of a drug’s chemical reactions with the calorimeter is the first step toward producing such a drug.”
The lab’s work on liver cancer imaging addresses another pressing health concern. The five-year survival rate for liver cancer is less than 30 percent, according to the NIH. “It’s hard to take an image of the liver because it’s so dark,” Korendovych says. “We need new ways to create specific probes so tumors in the liver light up.”
Korendovych and colleagues are using Syracuse’s calorimeter to research how a molecular probe selectively binds to proteins produced on the surfaces of liver cancer cells. The research aims to help doctors diagnose liver cancer so treatment can begin earlier. “It’s in the early stages,” Korendovych says. “We have some interesting preliminary data.”
The lab’s work in this area was featured on a 2019 cover of ChemCatChem, an interdisciplinary international journal on catalysis chemistry.
The paper reported the lab’s research on Leflunomide, a drug that suppresses the immune system. Leflunomide is processed in the liver to produce its active form (called teriflunomide) using “normal” human proteins. Researchers found they could create new ways of activating this drug using artificially created proteins of AlleyCat family. (AlleyCat is an acronym for ALLostEricallY Controlled cATalysts). Their research could allow drug makers to create a more effective form of Leflunomide.
“We’re looking at ways to make drugs work better,” Korendovych says. “Drugs are processed into something else. What gets produced is what makes it work.”
Regulating appetite with enzymes
Three members of the BioInspired Institute are researching an enzyme that plays a key role in regulating hunger. James Hougland, associate professor, and John Chisholm, professor, of the chemistry department in A&S; and Shikha Nangia, associate professor, Department of Biomedical and Chemical Engineering in the College of Engineering and Computer Science, along with graduate students and research associates were awarded a three-year, $960,000 NIH grant in September.
The group is studying how the enzyme GOAT (ghrelin O-acyltransferase) modifies ghrelin, a hormone that plays a number of roles in regulating metabolism. “Ghrelin is what literally makes you hungry,” Hougland explains. “Between meals, the amount of ghrelin in your bloodstream goes up and tells your brain that it’s time to eat.”
Ghrelin plays a role in regulating hunger and energy metabolism; insulin secretion and signaling; and neurological signaling pathways involved in substance use disorders. That suggests the team’s research could aid treatment for obesity, Type 2 diabetes and alcohol addiction, Hougland says.
When GOAT is activated, it attaches a short fatty acid to ghrelin. “Our work focuses on understanding how GOAT does that and how to block GOAT from doing that,” he says. Once these mechanisms are understood, scientists will have a clearer picture of how to control appetite.
Each lab contributes unique expertise to the project. Hougland’s lab works on protein biochemistry; Nangia’s lab uses computational modeling to predict the structure of GOAT; Chisholm’s lab makes the molecules and synthesize chemical probes to test if GOAT has been activated.
“We are working at the molecular level of understanding ghrelin,” Hougland says. “Ideally we would love our work to lay the foundation to make a new drug to treat diseases related to ghrelin. Even if we can’t develop new therapeutic treatment, the molecules we are developing will work as tools to better understand how ghrelin works.”
A month before the NIH grant was awarded, the Journal of Biological Chemistry published an article on the group’s research developing a structural model for GOAT. The authors include Syracuse faculty as well as undergraduate and graduate students.
“What really excites me about working on this problem is it can have real and lasting impact on human health,” Hougland says. “We’re going to get to the answer a lot faster if we address the problem on different scales simultaneously. No one lab, no one scientist is going to know it all or solve it all.”
While the research being done by students and faculty might start small on the molecular level, the results could be catalysts for major medical breakthroughs. For more information, visit the Department of Chemistry.