CIDR Seminar:
Speaker 1: Prof Nicholas King (Head of Discipline of Pathology, University of Sydney)
Title: Separating pathological from protective myeloid cell changes in response to infection
Abstract: The brain has a number of cellular defences that enable a quick response to infection, foremost among which, are cells of the myeloid lineage, including microglia and monocytes recruited from the bone marrow via the blood. However, the latter are frequently implicated in tissue damage associated with infection, and reducing the infiltration of these cells can dramatically improve disease outcomes. Microglia are relatively easy to define under homeostatic conditions, but difficult to distinguish from infiltrating monocytes over the course of disease, due phenotypic changes that occur in both cell types in response to infection. This makes it difficult to categorically define the identity, functions, interactions and relative contributions to disease of these cells. Using various models of infection, we are using clustering algorithms and temporal modelling approaches that have allowed us to make some progress on this problem, giving us a greater insight into the functional behaviour of these cells.
Biosketch: Nicholas King holds Medical and PhD degrees and is Professor and Head of Discipline of Pathology and Founding Director of a University of Sydney Core Facility, Sydney Cytometry. His long-standing research interests and principle contribution the field to date lies in how and why the immune response causes disease in response to infectious pathogens and specific approaches to intervention to ameliorate this.
Speaker 2: Dr Denuja Karunakaran (Associate Scientist, University of Ottawa Heart Institute)
Title: Beyond cell death: RIPK1 drives inflammation in atherosclerosis and immunometabolism in obesity.
Abstract: Chronic activation of the innate immune system drives inflammation and contributes directly to atherosclerosis, obesity and insulin resistance. RIP kinases (RIPK) are a member of serine/threonine family of kinases that have recently been shown to play an important role in cell death. We have previously shown that necroptosis, a pro-inflammatory form for programmed cell death, is activated in the vessel wall and drives atherosclerosis via activation of RIPK3 and its downstream target, MLKL. Here, we sought to determine upstream regulators of necroptosis in atherosclerosis and metabolic disease, and hypothesized that RIPK1, a key regulatory kinase upstream of NF-kB activation, apoptosis and necroptosis, drives immune cell inflammation in cardiometabolic diseases. Our studies identify a novel role for RIPK1 gene expression in atherosclerosis and obesity, and therapeutic knockdown of RIPK1 reduces disease progression. This seminar will explore the intricate yet distinct mechanisms by which genetic regulation of RIPK1 drives early atherosclerosis and diet-induced obesity.
Biosketch: Denuja Karunakaran, is an Associate Scientist at the University of Ottawa Heart Institute (UOHI), Canada. She completed her B. Biomed. Sci. (hons) and PhD in human platelet biology at Monash University, Australia. She then pursued the prestigious Heart Foundation Postdoctoral Fellowship at the University of New South Wales, Australia, followed by an Endowed Cardiovascular Genetics Postdoctoral Fellowship at UOHI. Her research interests include RIP kinases and microRNAs in inflammation, cell death and efferocytosis in coronary artery disease driven by psoriasis, thrombosis and obesity. She is a recent recipient of National Psoriasis Foundation Early Career Grant.