AIMRC Seminar: Review of Year Five AIMRC Pilot Projects

The Arkansas Integrative Metabolic Research Center will host Year Five Pilot Project Awardees Jeff Lewis, an associate professor of biological science, and Megan Rexius-Hall, an assistant professor of metabolic research, at 11:50 a.m. on Wednesday, Sept. 2, in Bell Engineering 2269. In this talk, they will discuss the results of their research. Two projects will be discussed:

Project Title

Global functional effects of post-translational protein modifications revealed through high-throughput CRISPR screens.

Abstract: When the environment changes abruptly, cells coordinate rapid response mechanisms such as post-translational protein modification to modulate protein activity. One such mechanism is reversible lysine acetylation, which until relatively recently was thought to solely regulate transcriptional processes. The surprising discovery of thousands of acetylated proteins in diverse organisms suggests a much broader role, but the function of acetylation remains unknown for the vast majority of proteins. One major tool used to interrogate the in vivo function of protein acetylation is the use of lysine substitution mutants that 'mimic' either acetyl-lysine or unacetylatable lysine. While a valuable approach, the pace of progress has been painfully slow, with one lysine per protein being tested at a time. Using brewer's yeast as a model, Lewis' lab developed a high-throughput CRISPR-based approach that examined about 8,000 lysine sites simultaneously under different physiological conditions, thus identifying hundreds of novel likely regulatory acetylation events.  

Biography: Jeff Lewis is a Southern California native who was introduced to research by David Low as an undergraduate at UC-Santa Barbara, where he worked on virulence gene regulation in uropathogenic E. coli. Despite the frigid winters, he fell in love with the University of Wisconsin during a recruitment visit and remained there to earn a Ph.D. in Microbiology in the lab of Jorge Escalante-Semerena. As a doctoral student, he studied the genetics and biochemistry of catabolism of unique carbon sources in Salmonella enterica. He made the jump to the dark side (eukaryotes) as a postdoctoral fellow in the lab of Audrey Gasch (UW-Madison as well), studying the genomics of yeast stress defense, and never looked back. Lewis' lab is currently interested in understanding how organisms sense and respond to stressful environments, and why certain genetically unique individuals are more susceptible or more resilient to stress.

Project Title

Engineering Pulmonary Hypertension In Vitro Using Clinical Pressure Waveforms

Abstract: Pulmonary arterial smooth muscle cells (PASMCs) play a central role in the vascular remodeling that drives pulmonary hypertension (PH), responding dynamically to changes in their mechanical and biochemical microenvironment. However, conventional in vitro models often rely on static culture conditions that fail to capture the dynamic pressure, oxygen, and mechanical cues experienced by PASMCs in vivo. To address this limitation, the Rexius-Hall laboratory developed an in vitro platform that enables controlled exposure of PASMCs to clinically relevant dynamic pressure waveforms while regulating oxygen tension. Current work has focused on the development, integration, and characterization of the platform and establishing reproducible microenvironmental control. Future studies will use this engineered system to determine how dynamic pressure and oxygen tension in combination regulate PASMC metabolism, reactive oxygen species production, proliferation, and viability. Overall, this platform provides a framework for dissecting the interactions between mechanical and metabolic stressors that contribute to PH-associated dysfunction.

Biography: Megan Rexius-Hall is a Robert E. Babcock Sr. Endowed Assistant Professor in the Ralph E. Martin Department of Chemical Engineering. She received her Ph.D. in Biomedical Engineering from the University of Illinois Chicago, co-advised in the Department of Biomedical Engineering and the Department of Pharmacology. She completed postdoctoral training in the Laboratory for Living Systems Engineering at the University of Southern California. Her work has been recognized with an AHA Postdoctoral Fellowship and NIH NHLBI Pathway to Independence Award (K99/R00). Rexius-Hall leads the Microphysiological Engineering Group (MEG), focusing on combining cell biology, materials science, and microfabrication techniques to engineer microphysiological systems with integrated functional metrics. Rexius-Hall envisions future research contributions using engineered microphysiological systems and in-depth functional and molecular analyses to uncover the mechanistic underpinnings of injury and disease states, identify druggable targets, and conduct preclinical drug screening.

This event is supported by NIGMS of the National Institutes of Health under Award Number 2P20GM139768. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Pizza and beverages will be served. Please contact Kimberley Fuller, fullerk@uark.edu, for more information.

For those unable to attend in person, this seminar will also be available via Zoom.