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CTN+ Postdoctoral Fellows Symposium

Saturday, May 3, 2025
7:45 - 9:00

Overview

Colloque des boursiers postdoctoraux du Réseau canadien pour les essais VIH des IRSC


Details

Meet the next generation of HIV and infectious disease researchers as they present an update on their CTN postdoctoral fellowships for 2024-2025. This is an excellent opportunity to see the future of research through the eyes of these young leaders. Anyone considering applying for a postdoctoral fellowship,or interested in shaping the new wave of research projects, should not miss this event. The recipients of the 2025-2026 CTN Postdoctoral Fellowships will also be announced during the session. Panelists: Dr. Monika M Kowatsch Down the Rabbit Hole: Calculating Lifetime Estradiol Exposure in a Cross-Sectional Study The sex hormone estradiol fluctuates with age and protects many body systems. Women living with HIV are more likely to experience states of low estradiol. Because assessing estradiol exposure at a single time point may not reflect or Inform on one’s exposure to the hormone, we propose a calculation to estimate lifetime estradiol exposure cross-sectionally. Dr. Hajar Miranzadeh HIV Infection of Human Glial Cells Causes Astrocyte Pyroptosis: Activation of Gasdermin B in NeuroHIV HIV-associated neurocognitive disorder (HAND) affects some people with HIV. In HAND brains, astrocytes showed high Gasdermin B (GSDMB) expression, with its cleavage causing plasma membrane rupture (PMR) and pyroptosis. Infected microglia showed minimal GSDMB expression. GSDMB levels in neural cells modulate their responses to HIV and contribute to neuroinflammation. Dr. Tanya Lazor Piloting an intervention for self-identified problematic cannabis use in people living with HIV Dr. Lazor will review her program of research which explores cannabis use among people living with HIV, including identification and application of an intervention for mitigating use among people in this population who have expressed an interest in modifying or reducing their use. *** Venez rencontrer la prochaine génération de chercheurs du domaine du VIH et des maladies infectieuses, qui font le point sur leurs bourses postdoctorales du RCE pour 2024-2025. Une occasion toute indiquée pour jeter un coup d’œil sur l’avenir de la recherche par les yeux de ces jeunes meneurs. Quiconque envisage de demander une bourse postdoctorale ou qui est intéressé à façonner la nouvelle vague de projets de recherche ne saurait rater cette occasion. Les bénéficiaires des bourses postdoctorales 2025-2026 du Réseau canadien pour les essais VIH seront également annoncés au cours de la séance.


Speaker

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Monika M. Kowatsch
Postdoctoral Fellow
University Of British Columbia

Down the Rabbit Hole: Calculating Lifetime Estradiol Exposure in a Cross-Sectional Study

Tanya Lazor
Postdoctoral Fellow
Centre For Addiction And Mental Health / CTN

Piloting an intervention for self-identified problematic cannabis use in people living with HIV

Hajar Miranzadeh Mahabadi
University Of Alberta

HIV Infection Causes Astrocyte Pyroptosis: Activation of Gasdermin B in NeuroHIV

Abstract

HIV-associated neurocognitive disorder (HAND) affects subset of persons with HIV (PWH). HAND is characterized by multifactorial mechanisms, including neuroinflammation, mitochondrial dysfunction and glial activation together with the release of viral proteins, which trigger neuronal injury/death, underpinning the associated neurological signs and symptoms. Inflammasome activation results in the activation and release of cytokines, associated with induction of pyroptosis, an inflammatory type of cell death driven by cleaved gasdermin proteins, causing plasma membrane rupture (PMR). Gasdermin B (GSDMB) transcripts and proteins including Ct-GSDMB were highly expressed in the brains of PWH with HAND. Immunofluorescence studies showed increased GSDMB expression in glial cells, chiefly in oligodendrocytes and astrocytes in brains with concurrent neuroinflammation from PWHs. Cultured HIV-infected human astrocytes displayed proteolytic cleavage of GSDMB, resulting in the appearance of Ct-GSDMB fragment that was accompanied by release of lactate dehydrogenase (LDH), indicative of PMR. We also found that the Nt-GSDMB domain containing exon-6 mediated PMR with concomitant mitochondrial damage that was evident as loss of membrane potential (TMRE). In contrast, HIV-infected microglia exhibited minimal GSDMB expression and did not undergo PMR and LDH release, despite productive HIV replication. In cultured primary human neurons, neurite length was decreased significantly following exposure to supernatants from HIV-infected primary microglia that confirmed neurotoxic soluble factors were released by infected microglia while supernatants from HIV-infected astrocytes did not alter neurite length. Among SIV-infected nonhuman primates, GSDMB immunoreactivity including Ct-GSDMB was evident in the brains of animals with encephalitis. Thus, GSDMB was expressed in specific glial cells within human brains and mediated pyroptosis in HIV-infected astrocytes. GSDMB expression levels in different neural cells can modulate their responses to HIV infection and contribute to neuroinflammation.

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