In December 2024, seven Internal Medicine pre- and postdoctoral researchers were honored with American Heart Association (AHA) fellowship awards. Our story about the five other AHA award recipients can be found here. We regret the omission of the following two award winners and are pleased to share their stories here.
In last year’s AHA award cycle, fewer than 30 percent of proposals were awarded funding. Michelle Tamplin, MS, PhD, postdoctoral research scholar, and Omar Rabab’h, MBBS, graduate research assistant and PhD candidate, were among those select few. The purpose of these prestigious AHA pre- and postdoctoral awards is to “enhance the training of applicants who are not yet independent” and in many cases to help recognize the unique challenges that clinicians experience in balancing research and clinical activity, flexibly allowing applicants to develop academic careers in research alongside fulfilling clinical service commitments.
Michelle Tamplin, MS, PhD, is a postdoctoral research scholar in the lab of Isabella Grumbach, MD, PhD, in the Division of Cardiovascular Medicine. Tamplin received a two-year, $161, 248 AHA postdoctoral fellowship award, and, with it, will use models of NADPH oxidase 2 (NOX2) inhibition to determine whether mitigation of oxidative stress in vivo protects microvessel structure and function and prevents cognitive decline after radiation therapy.
“Radiation-induced brain injury is observed in up to 90% of patients within 6 months of their radiation therapy (RT) for brain tumors or metastases. It significantly reduces quality of life after cancer treatment but has yet to be conclusively characterized in vivo,” Tamplin said. “One proposed mechanism for its development is progressive radiation damage to the microvessels, especially the microvascular endothelium, in the surrounding normal tissues which were exposed to off-target radiation.”
She explained that although studies have shown mitigation of oxidative stress may offer neurological protection after RT, it is unclear whether redox modulation (effectively balancing oxidation levels) in the brain’s endothelium is sufficient to prevent microvessel damage and cognitive decline. The lab hypothesizes that inhibiting NOX2-mediated oxidative stress in vivo will protect against “neurovascular uncoupling, microvessel rarefaction, ischemia, and cognitive decline” following cranial RT, making post-radiation recovery more comfortable and safer for patients in the long term.
If this study can establish the extent to which oxidative stress causes this dysfunction, identifying a new target for the prevention of radiation-induced cognitive impairment would prove to be a lifesaving tool in the future of cancer research.
In acknowledgment, Tamplin said, “I would like to thank my mentor, Dr. Isabella Grumbach, for her tremendous support and guidance. I also thank Grumbach lab members Anthony Vitale, Denise Juhr, and Dr. Olha Koval, as well as Drs. Bryan Allen and Michael Petronek from the Department of Radiation Oncology, for their assistance with the experiments and insightful scientific discussions. Their teamwork and encouragement make these studies not only possible, but also a lot of fun. A huge thank you also goes to our administrative staff–Dee Gansemer, Angie Hester, and Lori Strommer, to name a few–whose efforts help us focus more on the science, and less about the admin, side of grants.”
Omar Rabab’h, MBBS, and PhD candidate in Ryan L. Boudreau, PhD’s lab in the Division of Cardiovascular Medicine, received a two-year, $69,548 predoctoral AHA fellowship award . Rabab’h plans to study the regulation and dynamics of intercalated disc transcriptomes with the goal of identifying patterns in heart conditions.
Intercalated discs (ICDs) help cardiac cells communicate and work together, and their dysfunction can lead to a variety of heart diseases. Rabab’h explained that ICDs may also be sites where proteins are made locally in heart cells, prompting further study; researchers have found that ribonucleic acids (RNAs) are enriched at these ICDs, but only a few of these RNAs have been identified.
To learn more, the Boudreau lab developed a technique called “ICD-seq” to collect and study these ICDs from heart tissue. In ICD-seq, laser capture microdissection isolates the subcellular ICDs, then isolates and sequences their RNA. The lab found unique RNAs at the ICDs, many of which encode vital proteins involved in normal heart function, as well as some sequences that bind to proteins associated with heart disease. Studies in human heart tissue showed similar results to those in mice, indicating that these processes are conserved and important for full contextual understanding of cardiac pathologies.
“Our hypothesis is that select subsets of functionally related messenger RNAs (mRNAs) are trafficked to, anchored, and translated at the ICD via conserved mechanisms dependent on microtubules, molecular motors, and RNA-binding proteins. We believe that these processes are perturbed during cardiac stress, contributing to downstream detriments in heart function,” Rabab’h explained.
With the award, he plans to identify the specific RNA sequences, also termed “RNA ZIP codes,” that determine which RNAs go to ICDs and which do not. He also aims to identify the proteins that bind and help move these RNAs to ICDs, and to assess how ICD RNA profiles “re-wire” in cardiac stress and disease, using samples from mouse models of hypertrophy and heart failure as well as samples from humans with non-failing and failing hearts.
“I want to especially thank Dr. Boudreau for his support, guidance and insightful feedback, and Dr. Jared McLendon for his invaluable instruction, as well as the members of the Boudreau lab.”
Research initiatives like these enable UI Health Care to engage in groundbreaking research aimed at enhancing patient outcomes and eliminating obstacles to high-quality care. Congratulations to these exceptional researchers!
As always, if you have good news to share, let us know.