Dr Steve Kassem

RESEARCHER PROFILE

Postdoctoral Fellow

+61 2 9399 1128


Dr Steve Kassem completed his BSc at the University of Sydney in Neuroscience and Psychology. He then went on to complete his honours year at the Brain and Mind Research Institute, looking into the morphological changes of chronic stress on neurons, glia and gray matter. Where he published work revealing the composition of gray matter represented by its cellular bodies, and how changes to these cellular bodies resulted in concomitant changes in gray matter volume. Subsequently, he went on to complete his PhD, in a dual supervision, at the University of Sydney and the University of NSW, looking into the effects chronic stress and its morphological changes had on learning behaviours and their neural circuits. In addition, he modernised the Golgi Stain, a histological method over a century old and recognised as the gold standard to visualising the neuron, it fell out of common use due to it not being compatible with modern techniques, however, it now called the Ultra-Rapid Golgi or URG stain, and has revealed to be fluorescent and not only compatible but advantageous when combined with modern techniques. For his PhD, he won the Peter Bancroft Award for research excellence and a thesis which did not require emendment. Dr Kassem is an avid supporter of science communication and in 2017 joined NeuRA originally under the media and communications department, coming from his management role with the Sydney Science Festival, however as of 2018, Dr Kassem was appointed a postdoctoral fellowship to work with Scientia Professor George Paxinos AO, bringing his novel histological and MRI skills to Prof Paxinos’ work on visualising and defining the brain.

 

 

Projects Dr Steve Kassem is currently involved with

CURRENT PROJECTS

Caress the Detail: A Comprehensive MRI Atlas of the in Vivo Human Brain

This project aims to deliver the most comprehensive, detailed and stereotaxically accurate MRI atlas of the canonical human brain.

In human neuroscience, researchers and clinicians almost always investigate images obtained from living individuals. Yet, there is no satisfactory MRI atlas of the human brain in vivo or post-mortem. There are some population-based atlases, which valiantly solve a number of problems, but they fail to address major needs. Most problematically, they segment only a small number of brain structures, typically about 50, and they are of limited value for the interpretation of a single subject/patient.

In contrast to population-based approaches, the present project will investigate normal, living subjects in detail. We aim to define approximately 800 structures, as in the histological atlas of Mai, Majtanik and Paxinos (2016), and, thus, provide a “gold standard” for science and clinical practice. We will do this by obtaining high-resolution MRI at 3T and 7T of twelve subjects through a collaboration with Markus Barth from the Centre for Advanced Imaging at the University of Queensland (UQ). The limited number of subjects will allow us to image each for longer periods, obtaining higher resolution and contrast, and to invest the required time to produce unprecedented detail in segmentation.

We will produce an electronic atlas for interpreting MR images, both as a tablet application and as an online web service. The tablet application will provide a convenient and powerful exegesis of brain anatomy for researchers and clinicians. The open access web service will additionally provide images, segmentation and anatomical templates to be used with most common MR-analysis packages (e.g., SPM, FSL, MINC, BrainVoyager). This will be hosted in collaboration with UQ, supporting and complementing their population-based atlas.

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Caress the Detail: A Comprehensive MRI Atlas of the in Vivo Human Brain

THE ULTRA-RAPID-GOLGI STAIN

ARTICLE IN THE CONVERSATION

RESEARCH TEAM

DR TERI FURLONG Postdoctoral Fellow

DR CHRISTODOULOS SKLIROS PhD Fellow

KEIRA MCCLOSKEY Research Assistant

KATERINA ARVANITAKIS Research Assistant

PUBLICATIONS

A novel, modernized Golgi-Cox stain optimized for CLARITY cleared tissue.

Kassem MS, Fok SYY, Smith KL, Kuligowski M, Balleine BW

This is the first application of a Golgi-Cox stain to cleared brain tissue, it is investigated and discussed in detail, describing different methodologies that may be used, a comparison between the different clearing techniques and lastly the novel interaction of these techniques with this ultra-rapid stain.

Neuregulin 1 Deficiency Modulates Adolescent Stress-Induced Dendritic Spine Loss in a Brain Region-Specific Manner and Increases Complement 4 Expression in the Hippocampus.

Clarke DJ, Chohan TW, Kassem MS, Smith KL, Chesworth R, Karl T, Kuligowski MP, Fok SY, Bennett MR, Arnold JC

One neuropathological feature of schizophrenia is a diminished number of dendritic spines in the prefrontal cortex and hippocampus. The neuregulin 1 (Nrg1) system is involved in the plasticity of dendritic spines, and chronic stress decreases dendritic spine densities in the prefrontal cortex and hippocampus. Here, we aimed to assess whether Nrg1 deficiency confers vulnerability to the effects of adolescent stress on dendritic spine plasticity. We also assessed other schizophrenia-relevant neurobiological changes such as microglial cell activation, loss of parvalbumin (PV) interneurons, and induction of complement factor 4 (C4). Adolescent male wild-type (WT) and Nrg1 heterozygous mice were subjected to chronic restraint stress before their brains underwent Golgi impregnation or immunofluorescent staining of PV interneurons, microglial cells, and C4. Stress in WT mice promoted dendritic spine loss and microglial cell activation in the prefrontal cortex and the hippocampus. However, Nrg1 deficiency rendered mice resilient to stress-induced dendritic spine loss in the infralimbic cortex and the CA3 region of the hippocampus without affecting stress-induced microglial cell activation in these brain regions. Nrg1 deficiency and adolescent stress combined to trigger increased dendritic spine densities in the prelimbic cortex. In the hippocampal CA1 region, Nrg1 deficiency accentuated stress-induced dendritic spine loss. Nrg1 deficiency increased C4 protein and decreased C4 mRNA expression in the hippocampus, and the number of PV interneurons in the basolateral amygdala. This study demonstrates that Nrg1 modulates the impact of stress on the adolescent brain in a region-specific manner. It also provides first evidence of a link between Nrg1 and C4 systems in the hippocampus.

Stress-induced grey matter loss determined by MRI is primarily due to loss of dendrites and their synapses.

Kassem MS, Lagopoulos J, Stait-Gardner T, Price WS, Chohan TW, Arnold JC, Hatton SN, Bennett MR

Stress, unaccompanied by signs of post-traumatic stress disorder, is known to decrease grey matter volume (GMV) in the anterior cingulate cortex (ACC) and hippocampus but not the amygdala in humans. We sought to determine if this was the case in stressed mice using high-resolution magnetic resonance imaging (MRI) and to identify the cellular constituents of the grey matter that quantitatively give rise to such changes. Stressed mice showed grey matter losses of 10 and 15 % in the ACC and hippocampus, respectively but not in the amygdala or the retrosplenial granular area (RSG). Concurrently, no changes in the number or volumes of the somas of neurons, astrocytes or oligodendrocytes were detected. A loss of synaptic spine density of up to 60 % occurred on different-order dendrites in the ACC and hippocampus (CA1) but not in the amygdala or RSG. The loss of spines was accompanied by decreases in cumulative dendritic length of neurons of over 40 % in the ACC and hippocampus (CA1) giving rise to decreases in volume of dendrites of 2.6 mm(3) for the former and 0.6 mm(3) for the latter, with no change in the amygdala or RSG. These values are similar to the MRI-determined loss of GMV following stress of 3.0 and 0.8 mm(3) in ACC and hippocampus, respectively, with no changes in the amygdala or RSG. This quantitative study is the first to relate GMV changes in the cortex measured with MRI to volume changes in cellular constituents of the grey matter.

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