Suzanne Matsuura, Research Associate II, joins the laboratory.
Suzanne’s research focuses on the use of magnetic-electro-nanoparticles (MENP), coated with the anti-retroviral drug Tenofovir, as a delivery system to cross the BBB and treat HIV-1 infection in brain pericytes with the eventual aim of eradicating latent HIV reservoirs in the brain.
Suzanne’s laboratory expertise with molecular biology techniques and the handling of mammalian or bacterial cell culture comes from her previous work with Dr. Walter Scott (SV40 and HIV-1-RT systems) and Dr. Noriyuki Kasahara (viral vectors for cancer treatment). Formal training includes a Master of Science in Microbiology and Bachelor of Science in Biology and Chemistry.
She has been described as a ‘career technician with solid technical abilities and diligent work ethic’, but has been most appreciated by co-workers through the years for her compulsive baking.
Suzanne began working in the laboratory in January of 2019.
Oandy Naranjo joins the laboratory as a PhD student
Oandy, born in Cuba but a Miami native, received his Bachelor’s Degree in Biochemistry and Molecular Biology at Boston University in 2018. During his research as an undergraduate in the Department of Biology he worked on understanding Phagoptosis, a novel form of cell death that occurs in the ovaries of Drosophila melanogaster. In July of 2018 he started the Biomedical PhD program at the Miller School of Medicine and in December joined our lab. He is now working on understanding the role that platelet derived growth factor beta has on the integrity of the blood brain barrier and how that could change the course of HIV infection.
Oandy, welcome to the lab!
Martina’s paper accepted in Molecular Pharmaceutics
Congratulations to Martina for her paper that was accepted in Molecular Pharmaceutics (If 4.556) an undergraduate student in the laboratory! The paper is a collaborative work with Dr. Dhar (BMB) and Dr. Nair (FIU).
Velichkovska M, Surnar B, Nair M, Dhar S, Toborek M. Targeted mitochondrial CoQ10 delivery attenuates antiretroviral-drug-induced senescence of neural progenitor cells. Mol Pharm. 2019 Feb 4;16(2):724-736. doi: 10.1021/acs.molpharmaceut.8b01014.
HIV infection is associated with symptoms of accelerated or accentuated aging that are likely to be driven not only by HIV itself, but also by the toxicity of long-term use of antiretroviral drugs. Therefore, it is crucially important to understand the mechanisms by which antiretroviral drugs may contribute to aging. The aim of this study was to investigate the hypothesis that antiretroviral drugs cause increased reactive oxygen species (ROS) generation that results in mitochondrial dysfunction and culminates in promoting cellular senescence. In addition, we applied targeted nanoparticle (NP)-based delivery to specifically enrich mitochondria with coenzyme Q10 (CoQ10) in order to enhance antioxidant protection. The studies employed neural progenitor cells (NPCs), as differentiation of these cells into mature neurons is affected both during HIV infection and in the aging process. Exposure of cultured NPCs to various combinations of HIV antiretroviral therapy (ART) induced a more than two-fold increase in mitochondrial ROS generation and mitochondrial membrane potential, a more than 50% decrease in oxygen consumption and ATP levels, a 60% decrease in SIRT3 expression, and a 42% decrease in cell proliferation relative to control levels. These alterations were accompanied by a 37% increase in beta-galactosidase staining and telomeres length shortened to more half of the length of controls as assessed by quantitative telomere-FISH labeling, indicating accelerated NPC senescence in response to ART exposure. Importantly, targeted nanoparticles delivered by CoQ10 effectively attenuated these effects. Overall, these results indicate that ART promotes cellular senescence by causing mitochondrial dysfunction, which can be successfully reversed by supplementation with mitochondria-targeted CoQ10.
Luc’s and Joon’s manuscript accepted in Brain
Congratulations to Luc and Joon as their manuscript was accepted in Brain (IF 10.848)! They equally contributed to this excellent paper.
Bertrand L*, Cho HJ*, Toborek M. Blood-brain barrier pericytes as a target for HIV-1 infection. Brain. 2019 Mar 1;142(3):502-511. doi: 10.1093/brain/awy339.
Pericytes are multifunctional cells wrapped around endothelial cells via cytoplasmic processes that extend along the abluminal surface of the endothelium. The interactions between endothelial cells and pericytes of the blood-brain barrier (BBB) are necessary for proper formation, development, stabilization, and maintenance of the BBB. BBB pericytes regulate paracellular flow between cells, transendothelial fluid transport, maintain optimal chemical composition of the surrounding microenvironment, and protect endothelial cells from potential harmful substances. Thus, dysfunction or loss of BBB pericytes is an important factor in the pathogenesis of several diseases that are associated with microvascular instability. Importantly, recent research indicates that BBB pericytes can be a target of HIV-1 infection able to support productive HIV-1 replication. In addition, BBB pericytes are prone to establish a latent infection, which can be reactivated by a mixture of histone deacetylase inhibitors in combination with TNF. HIV-1 infection of BBB pericytes has been confirmed in a mouse model of HIV-1 infection and in human post-mortem samples of HIV-1-infected brains. Overall, recent evidence indicates that BBB pericytes can be a previously unrecognized HIV-1 target and reservoir in the brain.
Structural and molecular BBB pericyte connections within the neurovascular unit. (A) BBB pericytes (yellow) and endothelial cells (red) share the basement membrane (sky blue) or are in direct contacts. In addition, BBB pericytes are surrounded by glial cells (astrocytes, green; microglia, dark blue) and neurons (purple). (B) BBB pericytes and endothelial cells communicate with each other by direct contact (gap and adherens junctions) or through signaling pathways, such as platelet-derived growth factor B (PDGF-B)/PDGFRβ and transforming growth factor-β (TGF-β)/type 2 TGF-β receptor (TGFβR2
Marie Tournebize completed her research internship
As every year, this summer we also hosted an exchange student from France. Marie Tournebize studies Biology at Ecole Supérieure de Biologie-Biochimie-Biotechnologies (ESTBB) at the Université Catholique de Lyon. She completed her 4 month internship (from May 2018 to September 2018) in our laboratory. Her main mentor was Luc and the subject of her study was "HIV-induced vasculopathy and its impact on stroke". We were very pleased with her work and research progress. We thank Marie for her internship in our laboratory and wish her the best in the future.
Update: Marie is a coauthor of our recent Nature Communications paper: Bertrand L, Méroth F, Tournebize M, Leda AR, Sun E, Toborek M. Targeting the HIV-infected brain to improve ischemic stroke outcome. Nat Commun. 2019 May 1;10(1):2009. doi: 10.1038/s41467-019-10046-x.