Richelle Mychasiuk

Professor

Accepting PhD Students

PhD projects

Investigating the Role of the Circadian System in Traumatic Brain Injury
Investigating the Transition from Acute to Chronic Pain
The Effects of Orexin Modulation on Sleep, Glymphatic Function, and Recovery from Repetitive Mild Traumatic Brain Injury (TBI)

20092025

Research activity per year

Personal profile

Biography

I am Professor within the Department of Neuroscience at the School of Translational Medicine (STM), with an internationally recognised laboratory for the study of neurodevelopmental plasticity.  My laboratory uses extensive behavioural, epigenetic, imaging and neuropathological techniques to examine the influences of early experiences on long-term outcomes. We are particularly interested in understanding how early environmental manipulations (i.e. stress, drug exposure, diet) modify brain development and recovery from brain injury, as well as the risk for chronic pain and mental health disorders. In addition, we closely collaborate with the STM departments of Gastroenterology and Immunology as part of the new GIN (Gastroenterology-Immunology-Neuroscience) initiative which is designed to further understand the gut-brain-immune axis and rapidly translate research from the bench to the bedside.

I have held continuous national competitive funding throughout my academic career. As principal investigator, I was awarded an EL2 Investigator Grant from the NHMRC for $1.45M, a Canadian Institute for Health Research project grant for $1.2M, and a National Science and Engineering Research Council operating grant for $130K. I am the co-applicant on additional NHMRC Ideas grants examining the neurological consequences of traumatic brain injury (~$3M) neonatal infant abusive head injury ($1.2M), a CIHR Project grant ($600K), and a Chronic Pain Centre of Excellence for Canadian Veterans grant ($300K). I have also secured supplemental funding from three commercial/pharmacological sources (>$300K) and a co-PI on a 4th for $1.1M.

I was awarded the ‘Health Science Research Mentor Award’ from the
Faculty of Medicine (Calgary, CA) for my supervision of Honours students, in 2022 was nominated for Supervisor of the Year, at Monash University, and was the recipient of the Dean’s Award for Excellence in Diversity and Inclusion (Monash University, 2022).

Supervision interests

Investigating the Role of the Circadian System in Traumatic Brain Injury

Description 
Traumatic brain injury (TBI) is a complex and costly worldwide phenomenon that can lead to many negative health outcomes including disrupted circadian function. There is a bidirectional relationship between the immune system and the circadian system, with mammalian coordination of physiological activities being controlled by the primary circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN receives light information from the external environment and in turn synchronizes rhythms throughout the brain and body. The SCN is capable of endogenous self-sustained oscillatory activity through an intricate clock gene negative feedback loop. Following TBI, the response of the immune system can become prolonged and pathophysiological. This detrimental response not only occurs in the brain, but also within the periphery, where a leaky blood brain barrier can permit further infiltration of immune and inflammatory factors. The prolonged and pathological immune response that follows TBI can have deleterious effects on clock gene cycling and circadian function not only in the SCN, but also in other rhythmic areas throughout the body. This could bring about a state of circadian desynchrony where different rhythmic structures are no longer working together to promote optimal physiological function. There are many parallels between the negative symptomology associated with circadian desynchrony and TBI. This project will use preclinical models to examine mechanisms driving TBI-induced desynchrony in behaviour and neuropathology.

Investigating the Transition from Acute to Chronic Pain

Description 
Chronic pain initially presents itself acutely without indication that it will persist; making it difficult to catch before it develops and equally difficult to treat. Interestingly, the brain regions involved in acute vs. chronic pain differ. The regions involved in acute pain are primarily sensory, while chronic pain presents itself in regions of emotion. Our research aims to examine this transition from acute to chronic pain in an attempt to pinpoint where and why the shift occurs in order to better manage it.

The Effects of Orexin Modulation on Sleep, Glymphatic Function, and Recovery from Repetitive Mild Traumatic Brain Injury (TBI)

Description 
The system that is responsible for the clearance of macroscopic waste from the central nervous system is the glymphatic system. This waste removal system is radically inhibited during wakefulness, being 90% more active during sleep. The implications are astounding considering that sleep disturbances are regularly reported by traumatic brain injury (TBI) patients. The relationship between TBI and sleep problems could possibly explain the heightened neurodegenerative risk detected in epidemiological studies of TBI. The primary role of the neuropeptide orexin is to increase arousal levels and maintain wakefulness, thereby regulating the sleep-wake cycle. ORX-A is a nonselective agonist for the orexin receptors and is often used to treat narcolepsy; when ORX-A is administered sleep should be impaired, further limiting glymphatic function. Conversely, Suvorexant (SUV), a dual orexin receptor antagonist, is an FDA-approved drug that is administered orally for the treatment of insomnia. SUV inhibits binding of orexin A and B, thereby improving sleep. The specific purpose is therefore to examine sleep and glymphatic function following repetitive mild TBI, and whether or not short- and long-term neurological dysfunction is exacerbated when an orexin agonist is administered and ameliorated when an orexin antagonist is administered.

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being
  • SDG 4 - Quality Education
  • SDG 16 - Peace, Justice and Strong Institutions

Education/Academic qualification

Neuroscience, PhD

Award Date: 21 Jun 2012

Forensic Molecular Biology, Masters

Award Date: 30 Aug 2007

Psychology, BSc

Award Date: 1 Jun 2005

Cellular, Molecular, and Microbial Biology, BSc

Research area keywords

  • Mild traumatic brain injury
  • Neurodevelopmental plasticity
  • Concussion pathology

Collaborations and top research areas from the last five years

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