Nicole Stupka

Skeletal muscle repair and metabolism

Research overview

Nicole Stupka has a longstanding interest in the cellular mechanisms in skeletal muscle which promote adaptation to stress and enhance repair in order to improve tissue structure, function and metabolism. She is engaged in two key ongoing research themes instigated during her postdoctoral fellowship.

Firstly, investigating the consequences of nutrient excess on oxidative and endoplasmic reticulum stress responses in mature and regenerating skeletal muscle and the function the novel selenoprotein SEPS1 has in regulating these pathways. SEPS1 is highly expressed in skeletal muscle and polymorphisms have been implicated in diabetes, obesity and inflammation, although little is known about its underlying biochemistry and cell biology.

Secondly, to examine the role of secreted ADAMTS proteinases in extracellular matrix (ECM) remodelling during skeletal muscle development and regeneration, and to test the hypothesis that ADAMTS proteinases have therapeutic target potential for muscular dystrophy since appropriate ECM remodeling is essential for successful regeneration and optimal muscle function. As a result of her interest in oxidative stress and redox signalling, she has a cross-disciplinary collaboration with Analytical Chemistry to develop and validate novel approaches to measure cellular redox state (for example, reduced and oxidized glutathione).

Projects

1. The consequences of excess nutrients, specifically lipids, on oxidative and endoplasmic reticulum stress responses to in skeletal muscle and the downstream effects on metabolism and repair.
   
   
2. To characterize the function selenoprotein S (SEPS1) has in regulating cellular responses to oxidative and ER stress (with A/Prof Sof Andrikopoulos, Austin Health/The University of Melbourne, and Prof Ken Walder and Dr Nicky Konstantopoulos, School of Medicine, Deakin University).
   
   
3. The significance of extracellular matrix remodelling for skeletal muscle repair following injury and the role of ADAMTS enzymes in this process (with Dr Dan McCulloch, School of Medicine, Deakin University).
   
   
4. Development of innovative analytical techniques for glutatione and thiol determination and the validation of these technique in biological samples and cellular models of oxidative stress (with Dr Xavier Conlan, Dr Paul Francis and Prof Neil Barnett, School of Life and Environmental Science, Deakin University).

Now recruiting Honours and PhD students, please email expressions of interest to: nicole.stupka@deakin.edu.au

Figure 1: Elevated lipid levels activate oxidative and ER stress signaling pathways in diabetic skeletal muscle leading to dysfunction and compromised muscle health. We hypothesize that SEPS1 is a protective target gene and when upregulated promotes adaptation to improve muscle regeneration and metabolism.

Figure 2: To assess cellular redox state andoxidative stress, we use HPLC coupled with chemiluminscent detection to directly measure reduced and oxidized gluthatione in biological samples, for example cultured skeletal muscle cells.

Biography

Nicole Stupka began her research career studying the adaptations to acute exercise-induced muscle damage in healthy human subjects and the mitigating effect of gender on muscle damage responses and subsequent adaptation as part of an MSc (2000) in exercise physiology from McMaster University. She then completed a PhD (2006) in Skeletal muscle physiology from The University of Melbourne investigating calcineurin signalling as a therapeutic target to alleviate the pathology of Duchenne muscular dystrophy and to improve skeletal muscle regeneration. She then moved to Deakin with support of an NH&MRC Biomedical (Peter Doherty) Training Fellowship.

View Dr Nicole Stupka's publications