Seminar
Professor, Department of Pharmacology & Toxicology, University of Arizona
"RNA Binding Proteins and Neurodegenerative Diseases"
Host: Andrew Paek
RNA binding proteins and dysregulation of RNA metabolism are an emerging theme in neurodegenerative diseases. We will discuss the RNA binding protein Fused in Sarcoma (FUS) whose mutations are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Our laboratory has characterized the wild-type and disease-causing mutants of FUS using a variety of approaches including proteomics, biochemistry, cell biology and genetic models. Our recent studies show that the ALS/FTD mutations of FUS suppress protein translation and dysregulate mRNA decay. We will also discuss the post-translational modifications, particularly acetylation, of FUS that regulate its subcellular localization, RNA binding, and formation of protein-RNA condensates.
When
11 a.m. to 12:15 p.m. Nov. 16, 2021
Location
ENR2 Room S107
Postdoc, Molecular & Cellular Biology, University of Arizona
"Not all kinases act as a switch: condition specific signaling through Protein Kinase A"
Host: Andrew Capaldi
Models of cellular processes are frequently based on all-or-nothing statements. E.g. a kinase may be active and phosphorylate all of its targets – or not. In this presentation, I showcase results that highlight the need for a more refined perspective. To improve our understanding of Protein kinase A (PKA) signaling in S. cerevisiae, we determined novel PKA-substrates by phospho-proteomics. Interestingly, we found that some of these proteins are also phosphorylated under a condition where PKA was believed to be inactive. We demonstrated that the phosphorylation level in this condition is highly correlated to a measure of in vivo substrate quality we derived. Based on these results, we propose a model in which substrates of the same kinase yield condition-dependent sets of phosphorylated proteins, which are a function of kinase activity and substrate quality. We are now exploring the molecular basis for PKA-substrate quality.
When
11 a.m. to 12:15 p.m. Nov. 23, 2021
Location
Zoom Link TBA
Host: Daniela Zarnescu
"Mechanisms of nucleostasis in neuronal health and disease"
Maintenance of nuclear pore complex (NPC) and nuclear envelope (NE) structure, organization, and function is essential for cellular function. The NPC and NE critically controls multiple cellular processes including nucleocytoplasmic transport (NCT), gene expression, genome organization, and maintains nuclear – cytoplasmic compartmentalization. Alterations to the composition and function of the NPC have recently emerged as an early and significant contributor to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS) and related neurodegenerative diseases. However, the molecular events leading to this pathological phenomenon remain largely unknown. Using induced pluripotent stem cell (iPSC) derived neurons (iPSNs), postmortem human tissues, and super resolution structured illumination microscopy (SIM), I have comprehensively defined a significant injury to the nuclear pore complex (NPC) as one of the earliest events in ALS pathophysiology. This injury is characterized by the reduction of specific nucleoporins, beginning with POM121, from the neuronal NPC. Mechanistically, I have uncovered that aberrant nuclear accumulation of the ESCRT-III protein CHMP7 initiates NPC injury in ALS to functionally impact nucleocytoplasmic transport, nuclear TDP-43 function and localization, and overall neuronal survival. Critically, reduction of CHMP7 protein mitigates NPC injury and downstream pathogenic events in ALS iPSNs. Collectively, this work has identified a new pathway implicated in neurodegenerative disease pathophysiology that can be therapeutically targeted to alleviate prominent pathogenic cascades.
When
11 a.m. to 12:15 p.m. Oct. 26, 2021
Location
https://arizona.zoom.us/s/83888998594
Session is password protected. Contact dslay@arizona.edu.
"Molecular networks and enzymes that play a central role in COVID-19 mortality"
Floyd (Ski) Chilton, Professor, School of Nutritional Sciences and Wellness, The University of Arizona
Host: Guang Yao
When
11 a.m. to 12:15 p.m. Oct. 19, 2021
Location
ENR2 Room S107
Host: Ryan Gutenkunst
When
11 a.m. to 12:15 p.m. Oct. 5, 2021
Location
ZOOM
When
11 a.m. to 12:15 p.m. Sept. 28, 2021
When
11 a.m. to 12:15 p.m. Oct. 12, 2021
Location
ENR2 Room S107
The University of Arizona
Molecular & Cellular Biology
Host: Guang Yao
When
11 a.m. to 12:15 p.m. Sept. 14, 2021
Location
ENR2 Room S107
Associate Professor, Plant Sciences
The University of Arizona
Host: Ross Buchan (MCB)
When
11 a.m. to 12:15 p.m. Sept. 21, 2021
Location
ENR2 Room S107
The University of Arizona
Host: Andrew Paek
When
11 a.m. to 12:15 p.m. Sept. 7, 2021
Location
ENR2 Room S107