Collaborate 2 Cure
May 8, 2017



KU Clinical Research: Fairway Auditorium
4350 Shawnee Mission Parkway Fairway, KS 66205

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The Sweet Side of Mitochondrial Regulation


Currently, 5.4 million Americans are suffering from Alzheimer’s disease (AD).  The stress on the health care system and families is increasing with the cost for treating AD individuals reaching $183 billion in 2011 (Alzheimer’s Association fact sheet).  Furthermore, AD is the only major disease in which there is no good prevention methods, treatments, or a cure.  AD brains are diagnosed by fibrous aggregation containing a large proportion of the amyloid protein.  However, is the accumulation of these plaques the cause or physical manifestation of the disease? New ways of looking at AD are critical for understanding the biological mechanisms leading to AD pathology.  Accumulating evidence suggests that AD is caused by the age related impairment of mitochondrial function leading to increased reactive oxygen species production, cellular damage, and inflammation. One potential mechanism regulating metabolic function is O-GlcNAc signaling. O-GlcNAc is a ubiquitous protein modification consisting of a single N-acetylglucosamine moiety attached to serine/threonine residues found on cytoplasmic and nuclear proteins. O-GlcNAc dynamically cycles on and off proteins by the actions of O-GlcNAc transfease (OGT) and O-GlcNAcase (OGA) respectively in response to environmental changes. Disruptions in O-GlcNAc cycling are linked to AD, but how altered cycling of O-GlcNAc contributes to AD etiology is unclear.  We contend that O-GlcNAcylation is a key regulator of metabolic function and alterations in O-GlcNAcylation contribute to the development and progression of AD. Here, we report that sustained alterations in O-GlcNAcylation either by pharmacological or genetic manipulation alters metabolic function. O-GlcNAc elevation reduces cellular respiration and ROS generation, and elongates mitochondria in neuroblastoma cells. Sustained O-GlcNAcylation in mice brain and liver validates the metabolic phenotypes seen in cells, whereas, liver OGT knockdown elevates ROS levels, impairs respiration, and increases NRF2 anti-oxidant response. Elevated O-GlcNAc promotes weight loss, lowers respiration, and skews mice toward carbohydrate dependent metabolism. In summary, sustained elevation in O-GlcNAcylation coupled with increased OGA expression reprograms energy metabolism potentially impacting the development of AD.

Speaker- Chad Slawson, PhD

Chad Slawson is an assistant professor in the department of Biochemistry and Molecular Biology at the University of Kansas Medical Center.  Dr. Slawson received his undergraduate degree in Biochemistry from Indiana University and then his Ph.D. from the University of South Florida.  Next, he was a post-doctoral fellow at the Johns Hopkins School of Medicine.  Dr. Slawson joined KUMC in 2011.  Since his arrival, his laboratory has published 11 papers on the role of O-GlcNAc in human health and disease.  He has received funding from the National Institute of Health and the University of Kansas.

Mitochondrial Function of Complement 1q Binding Protein


The mitochondrial permeability transition (MPT) pore regulates necrotic cell death following diverse cardiac insults and, therefore, contributes to many cardiac pathologies. However, so far the only confirmed component of the pore is Cyclophilin D (CypD). Our laboratory has identified complement 1q-binding protein (C1qbp) as a novel CypD-interacting molecule and a negative effector of MPT-dependent cell death. C1qbp is an acidic homotrimer with proposed roles in inflammation, cancer progression, biogenesis of respiratory chain components and overall mitochondrial ultrastructure. However, its effects in the cardiac system remain untested, especially with regards to cardiac pathogenesis. This presentation will focus on our current studies examining the role of C1qbp in cardiac mitochondrial function/dysfunction and how its manipulation may modify the progression of cardiac disease.

Speaker- Chris Baines, PhD

Dr. Chris Baines is an Associate Professor in the Department of Biomedical Sciences and the Dalton Cardiovascular Research Center at the University of Missouri-Columbia. Chris’ main research interest is in mitochondria and their role in cardiomyocyte death and the progression of cardiac disease. Specifically, he is interested in identifying the molecular components of the mitochondrial permeability transition pore. Moreover, he is looking at the mechanisms of programmed necrosis in the heart, and how mitochondria fit into these pathways.