Joseph Burclaff, research assistant professor in the Joint Department of Biomedical Engineering, was recently awarded the 2024 AGA-Bristol Mayers Squibb Research Scholar Award in inflammatory bowel disease through the American Gastroenterological Association. Burclaff was selected for this prestigious award for his work studying the biological mechanisms underlying intestinal stem cell dysfunction. This award will support his focus on understanding how transcription factors may promote gut inflammatory responses like those seen in inflammatory bowel disease (IBD) patients.
Written by Kathleen Clardy for the Joint Department of Biomedical Engineering
The AGA-Bristol Mayers Squibb Research Scholar Award is provided to only one applicant per year and funds $300,000 over three years. The award will support Burclaff in studying how transcription factors affect how mitochondria function within the intestinal lining. Since many transcription factor regulators of mitochondria likely exist that have not been studied, Burclaff’s research will help fill a research need for a better understanding of how and when genes can cause exaggerated inflammatory responses.
“The gastrointestinal tract provides exciting ways to study stem cells since the lining of the stomach and intestine are continually replaced by adult stem cells which reside in the organs throughout your life to maintain the cell types that provide proper barrier function, break down and digest food, and protect the body from pathogens,” Burclaff explained. “Little is known about what controls the earliest changes as inflammatory bowel diseases (IBD) start to develop. Intestinal stem cells are critical for normal maintenance and repair of the gut lining, so any defect in stem cells may promote early damage and weaken injury repair, leading to IBD initiation.”
Previous studies show healthy areas of the intestinal lining of IBD patients show a decrease in mitochondrial activity and higher expression of pro-inflammatory genes. Since mitochondria are the energy-producing organelles that power the cells of the body, this decreased activity may inhibit normal maintenance and repair of the gut lining. Without this function, the gut lining is more prone to damage and injury, likely contributing to the initiation of IBD.
“I previously studied cultured intestinal stem cells from human donors and experimentally increased expression of SOX9, a transcription factor protein that controls genes that are expressed,” explained Burclaff. “I found high SOX9 decreases mitochondrial activity, which is important for stem cells to maintain the gut lining, and subsequently increases genes that promote inflammation.”
SOX9 driving changes that mimic IBD in healthy stem cells highlight a way that the healthy intestine may become susceptible to injury and impair wound responsiveness, leading to chronic inflammation. Previous research also connects high SOX9 expression within certain patients with Crohn’s disease, a common subset of IBD. Burclaff plans to study Crohn’s disease patient tissue samples to determine whether these factors also associate with this disease or predict treatment response.
“This may allow clinicians to predict Crohn’s disease risk before it occurs and provide new prevention strategies,” Burclaff said. “This award will directly set up future work testing whether these factors promote inflammation and present new therapeutic options for treating or preventing IBD.”
“The AGA Research Foundation is proud to fund these investigators and their ongoing efforts to advance GI research at a critical time in their careers. We believe the Foundation’s investment will ultimately enable new discoveries in gastroenterology and hepatology that will benefit patients,” said Michael Camilleri, MD, AGAF, chair of the AGA Research Foundation.
“The American Gastroenterological Association does so much to support patients and researchers,” Burclaff added. “This grant will support me as I begin studying IBD and immersing myself in disease-focused research. Not only will I be mentored by physician-scientists who directly treat IBD, but I’ll be studying patient samples and have the opportunity to meet patients themselves to see what impact my work may have on their future therapy.’
For more information about the AGA Research Foundation Awards Program, please visit gastro.org.
To learn more about Joseph Burclaff and his work on understanding how transcription factors are related to inflammatory bowel diseases, please visit this page.