My research focuses on the molecular/mechanistic understanding of how sex steroid signaling and neuroinflammation interact and contribute to striatal and cortical modulation of dopamine and how dopamine-related behaviours (psychotic-like symptoms, memory and cognition) are altered by sex steroids in male and female rats of different ages. The goal is to transfer this knowledge to human studies to develop or enhance sex...view more
My research focuses on the molecular/mechanistic understanding of how sex steroid signaling and neuroinflammation interact and contribute to striatal and cortical modulation of dopamine and how dopamine-related behaviours (psychotic-like symptoms, memory and cognition) are altered by sex steroids in male and female rats of different ages. The goal is to transfer this knowledge to human studies to develop or enhance sex steroid based and immune-related treatments for the cognitive and psychotic symptoms of schizophrenia in an age and gender specific manner.
PhD (Neuroscience) Manchester University, UK
MSc (Chemical Pathology), University of Cape Town, SA
Honours (Pharmacology), University of Cape Town, SA
BSc (Botany, Biochemistry), University of Cape Town, SA
My Research Activities
Preclinical studies ask how sex steroid-related, dopamine-related (and other neurotransmitter systems) and immune-related gene and protein expression in the midbrain (and other brain regions) are altered in the maternal immune activation (MIA) model in offspring with high and low inflammation. We can measure inflammation markers and sex steroids in the periphery and relate this to behavior and to gene and protein expression in different brain regions, and we can do this in both genders and longitudinally (i.e juvenile, adolescence, adulthood). It is unknown whether schizophrenia patients move in and out of high inflammation status and how this relates to cognitive decline and psychotic episodes or how it is related to antipsychotic treatments or if it changes with changing circulating hormone levels. I will address these questions in the MIA model.
Significance: Understanding sex steroid-induced schizophrenia-related behaviours in the context of neuroinflammation and the dopamine neurotransmitter system in midbrain, cortex and striatum in both sexes will provide new knowledge that will lead to new treatment targets with a focus on individualized treatment (i.e. by sex and inflammatory status).
The midbrain, although critical to dopamine regulation is surprisingly understudied in the context of schizophrenia, especially in the postmortem field. We use a postmortem midbrain cohort in the Schizophrenia Research Laboratory with 30/30 cases/controls. Our research has identified dysregulation of multiple DA-related transcripts (Purves-Tyson, Translational Psychiatry 2017) and high and low immune groups in this cohort. As I identify further molecular targets in the MIA model, these will be interrogated in the schizophrenia midbrain cohort. In a converse fashion, we plan to sequence the transcriptome in this 30/30 control/schizophrenia midbrain cohort to allow the brains to inform the pathways and molecules we investigate/manipulate in the MIA model. This would provide the first database of the molecular signature of schizophrenia in the midbrain.
My Research Supervision
Areas of supervision
1. The interaction between sex steroids and neuroinflammation and their role in the dopamine dysregulation in the maternal immune activation rat model and underlying psychosis and cognitive deficits in schizophrenia
2. Determining the molecular underpinnings of improved cognition induced by estrogen receptor modulation
Honours: GABAergic-related Gene Expression in the Midbrain in Schizophrenia and a Rodent Maternal Immune Activation Model
PhD: Altered N-Methyl-d-Aspartate Receptor composition and gene expression in dorsolateral prefrontal cortex of schizophrenia cases with elevated inflammatory markers
PhD: Understanding the role of androgens and dopamine in the pathogenesis of schizophrenia