2025 SPARK grants spur research efforts across departments

The Department of Medicine’s Steffan Nawrocki, PhD, and Jennifer Stern, PhD, both landed Spark Grants from the University of Arizona College of Medicine – Tucson earlier this fall.

The two each got the maximum award of $45,000.

A professor in the newly reinstated Division of Translational Medicine, Dr. Nawrocki’s funded study is titled “Dual brain-penetrant histone deacetylase (HDAC) and autophagy inhibitors for glioblastoma therapy” — glioblastoma being the most aggressive and common form of brain cancer. The award is in partnership with Kristin Huntoon, DO, PhD, a Department of Neurosurgery assistant professor who joined the college’s faculty in August 2024 as a fellowship-trained brain and spine tumor neurosurgeon from Emory University and MD Anderson Cancer Center.

A Division of Endocrinology assistant professor, Dr. Stern’s study is titled, “The role of glucagon signaling in the cholesterol lowering effects of plant-based fiber consumption.” It continues her research into caloric restriction, glucagon signaling and its effects on healthy aging. She won the award with investigative partner Frank Duca, PhD, associate professor of integrative biology and physiology at the University of Minnesota.

Other Spark awards

“This year, we awarded five Spark grants,” said Nicole Schmidt, PhD, the college’s assistant director of research and graduate studies, who oversees the Spark and FUTURRE grant programs for the college.

The other awards — including winners’ home departments, amount and study titles — went to:

• Erika Eggers, PhD (Physiology), and Lalitha Madhavan, MD, PhD* (Neurology) – $45,000 – “Retinal visual dysfunction – A window into the Parkinsonian brain”

• Elise Erickson, PhD (Physiology), and E. Fiona Bailey, PhD (Physiology) – $34,063 – “Breathing for two: Inspiratory muscle strength training for supporting healthy blood pressure in pregnancy” 
• Anita Koshy, MD* (Neurology) and Sarah Ewald, PhD (University of Virginia Department of Microbiology, Immunology and Cancer Biology) – $45,000 – “Defining how human neurons control a common brain parasite” 

(*Dr. Madhavan has a dual appointment in the DOM’s Division of General Internal Medicine, Geriatrics & Palliative Medicine, and Dr. Koshy has one in Immunobiology and the DOM’s Division of Infectious Diseases.)

Winning notices for this year’s Spark awards, begun in 2022, went out in late October and early November. The awards are designed to provide nine-month, quick-start funds to spark new and collaborative research, Schmidt said. Funding is provided to generate preliminary data in preparation for submission of competitive federal grant applications. Investigators are welcome to apply for these grants via the AZ Cultivate competition space. The RFA (request for proposals) is usually open from late summer to early fall each year via this portal. The number of grants awarded depends on the annual budget, she added.

Dual attack on brain cancer

Dr. Nawrocki emphasized the formidable challenges posed by brain cancers, including its aggressive biology and the difficulty of delivering treatment regimens across the blood-brain barrier. This protective barrier is a natural shield the brain employs to protect itself from harmful substances, but also limits the penetration of promising therapeutics.

HDAC inhibitors are a class of drugs that block the action of histone deacetylase enzymes that are approved for treating certain cancers such as lymphomas, but have shown only modest activity against glioblastoma. Dr. Nawrocki said, although HDAC inhibitors do stimulate cancer cell death, they also can activate a pro-survival pathway called autophagy** that helps the cell survive by recycling intracellular components. This dual action has led many in the field to propose that combination therapies targeting HDACs and autophagy simultaneously may produce more meaningful anti-tumor effects.

(**Autophagy is the body’s natural process for cleaning out damaged cells, recycling old components like proteins and organelles, and generating energy to maintain health and survive stress.)

The Spark Grant project matches Dr. Nawrocki’s expertise in designing brain-penetrant small molecules that inhibit autophagy with that of Dr. Huntoon, who is co-chair for several committees on the Tumor Section of the American Association of Neurological Surgeons. This study builds on Dr. Nawrocki’s prior work demonstrating that inhibition of autophagy disrupts breast cancer brain metastasis.

“Essentially, cancer cells are very smart and they want to survive,” he said. “When we hit them with an HDAC inhibitor, they activate autophagy to try to generate the energy needed to survive. We are shutting down that process and, in doing so, we see synergistic anti-cancer activity when we block HDACs, and also block autophagic degradation. Here, we’re developing these novel drugs that do both simultaneously, and that's what we want to test in this grant.”

High-fiber diets, lower LDLs and longer life

Dr. Stern’s grant focuses on understanding mechanisms behind how a high-fiber diet increases glucagon, a hormone naturally produced by the pancreas that regulates insulin in the blood, which may not only help lower weight but cholesterol levels as well.

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Obesity, she notes, increases likelihood of high cholesterol levels in the blood — particularly LDL or “bad” cholesterol — leading to fat buildup, or atherosclerosis, in arteries, which increases risk of heart attack, stroke and cardiovascular disease, the U.S.’s leading cause of death, often due to genetics (familial hypercholesterolemia) or lifestyle.

“Still, only about 50% of people who might benefit from cholesterol-lowering medication are currently taking these medications,” Dr. Stern said. Her lab has established that glucagon receptor agonism — via compounds that boost glucagon signaling — effectively and robustly lowers cholesterol in obese mice and that increasing fiber intake can lower cholesterol in both humans and rodents.

“Mechanisms by which increasing fiber intake and glucagon receptor agonism lower cholesterol are overlapping, suggesting that the cholesterol-lowering effects of high-fiber intake could be mediated through enhanced glucagon signaling at the liver,” she added.

She and Dr. Duca will evaluate the role of glucagon signaling in mediating the lipid-lowering effects of plant-based fibers. These studies hold the potential to identify glucagon as a novel player in the regulation of the gut-liver axis, increasing the potential for the development of novel lipid-lowering therapeutics.

All the studies — including Dr. Stern’s and Dr. Nawrocki’s — will wrap up their work by next summer and lay the groundwork for applications for further research funding via the National Institutes of Health and other sources.

ALSO SEE:
“‘Hallmarks of Aging’ a topical dynamo at 2nd SOAR in DOM Forum” | Posted Nov. 26, 2025
“University of Arizona scientist links calorie restriction, glucagon and healthy aging” | Posted Oct. 30, 2025
“Study identifies potential pathway to reducing breast cancer brain metastases” | Posted June 17, 2024