Description:

Alexis Demonbreun, Ph.D.
Research Assistant Professor
Department of Pharmacology and Center for Genetic Medicine

Title: Genetic modifiers of muscle disease as therapeutic targets

Abstract: Muscular dystrophy is a group of diseases characterized by progressive muscle wasting, membrane fragility, and fibrosis, often caused by mutations in membrane-associated and cytoskeletal proteins. In both mice and humans, disease severity is highly dependent on genetic background. Using a genome-wide scan and quantitative trait loci (QTL) mapping we identified two genes, Latent TGF-B binding protein 4 and annexin A6, as modifiers of fibrosis and membrane leak/repair. My current work is aimed at developing biologics to target these two genetically defined pathways to delay dystrophy progression and improve muscle function. 

Michaela Novakovic 
Ph.D. Candidate in Dr. Murali Prakriya Laboratory

Title: The role of astrocyte calcium signals in production of cytokines and modulation of synaptic function

Abstract: Astrocytes release cytokines in a growing list of pathologies that exhibit altered synaptic function, including Alzheimer’s Disease. However, it is unclear how these cytokines are produced and how they contribute to synaptic dysfunction. The goal of my project is to understand how cytokines are regulated by astrocytic store-operated calcium entry (SOCE) and how they affect synaptic function. My results show that astrocytes rely on SOCE for the production of multiple cytokines through regulation of transcription factors NFAT and NFκB. I am testing the effects of these cytokines on neuronal function through glutamate uncaging and calcium imaging with GCaMP6f. My preliminary results indicate that conditioned media from thrombin-stimulated astrocytes induces an increased glutamate response in spines. Understanding the role of astrocytic SOCE in inflammation will further our understanding of how astrocytes modulate neuronal function in health and disease.