Comprehensive Cancer Center, Lab 332 (Wojna Lab) Department of Microbiology and Medical Zoology, University of Puerto-Rico-School of Medicine Medical Sciences Campus P.O. Box 365067, San Juan, P.R. 00936-5067
(787) 758-2525, X-2819
• B.S. Biology, Univ. of Puerto Rico, Río Piedras, P.R. 2005 • Ph. D. Microbiology and Medical Zoology, Univ. of Puerto Rico, Medical Sciences, P.R. 2016 • Post-doc Mechanisms of HIV-associated neuronal dysfunction, Univ. of Puerto Rico, Medical Sciences, 2018 • Post-doc Monocyte immune responses in neurodegenerative disorders, Univ. of Puerto Rico, Medical Sciences
Chronic inflammation affects people living with HIV (PHW) and leads to the development of HIV-related and non-HIV-related comorbidities including metabolic syndrome, cardiovascular disease, opportunistic infections, HIV-associated neurocognitive disorders (HAND), among others. HAND is of special concern because it affects 20-50% of HIV-positive patients despite the efficacy of modern combined antiretroviral therapy (cART) and improved quality of life, and there are no effective therapies available. Some mechanistic aspects associated with HAND include increased peripheral monocyte and macrophage activation; secretion of pro-inflammatory cytokines, chemokines, and viral proteins; invasion of HIV-infected cells, and proinflammatory factors into the central nervous system (CNS); infection of microglia; activation of CNS resident cells; and neuronal injury. The specific roles of peripheral monocytes/macrophages (Mφs) in the neuropathogenesis of HIV are not fully understood. Our research project aims to determine how dysregulation of the innate immune responses in Mφs contribute to inflammation, neuronal dysfunction, and cognitive impairment in PWH. We are establishing human 3D brain organoids co-cultured with patient-derived monocytes, to model immune cell invasion to the CNS and study monocyte-neuron interactions in vitro. Our approach includes a combination of several techniques including: flow cytometry, immunoassays, single-cell RNA sequencing, and CRISPR/Cas9, to characterize monocyte populations, neuronal damage markers and disrupted signaling mechanisms. We will expand the brain organoids techniques to study other neurodegenerative diseases, such as Alzheimer’s disease, and develop additional 3D cultures, as part of our collaborations.
Cantres-Rosario YM, Ortiz-Rodríguez SC, Santos-Figueroa A, Plaud M, Negron K, Cotto B, Langford TD and Melendez LM. (2019) HIV Infection Induces Extracellular Cathepsin B Uptake By Neurons, Triggering Apoptosis And Synapse Loss. Scientific Reports 9:8006. doi: 10.1038/s41598-019-44463-1
Rosas-Vidal LE, Lozada V, Cantres-Rosario YM, Vega-Medina A, Melendez L, and Quirk GJ. (2018) Alteration of BDNF in the medial prefrontal cortex and the ventral hippocampus impairs extinction of avoidance. Neuropsychopharmacology. doi:10.1038/s41386-018-0176-8
Cantres-Rosario YM, Acevedo-Mariani FM, Perez-Laspiur J, Haskins WE, Plaud M, Cantres Y, Skolasky R, Mendez-Bermudez I, Wojna V, Melendez LM. (2017) Microwave & Magnetic Proteomics of Macrophages from Patients with HIV-Associated Cognitive Impairment. PLoS ONE Jul 26;12(7): e0181779. PMID: 28746408.
Martínez-Rivera FJ, Pérez-Laspiur J, Santiago-Gascot ME, Alemán-Reyes AG, García-Santiago E, Rodríguez-Pérez Y, Calo-Guadalupe C, Otero-Pagán I, Ayala-Pagán RN, Martínez M, Cantres-Rosario YM, Meléndez LM, Barreto-Estrada JL. (2017) Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids. PLoS ONE Jul 18;12(7): e0180409. PMID: 28719635.
Cantres-Rosario YM, Hernandez N, Negron K, Perez-Laspiur J, Leszyk J, Shaffer S, et al. (2015) Interacting partners of macrophage-secreted cathepsin B contribute to HIV-induced neuronal apoptosis. AIDS: 29:1. PMCID: PMC4636939
Zenón F, Cantres-Rosario Y, Adiga R, Gonzalez M, Rodriguez-Franco E, Langford D, et al. (2015) HIV-infected microglia mediate cathepsin B-induced neurotoxicity. J Neurovirol, 21(5):544-58. PMCID: PMC4618197
Rivera LE, Colón K, Cantres-Rosario YM, Zenón FM, Meléndez LM (2014) Macrophage Derived Cystatin B / Cathepsin B in HIV Replication and Neuropathogenesis: 111–120. PMCID: PMC4122617
Cantres-Rosario YM, Plaud-Valentín M, Gerena Y, Skolasky RL, Wojna V, et al. (2013) Cathepsin B and cystatin B in HIV-seropositive women are associated with infection and HIV-1-associated neurocognitive disorders. AIDS 27: 347–356. PMCID: PMC3593054
Rodriguez-Franco EJ, Cantres-Rosario YM, Plaud-Valentin M, Romeu R, Rodríguez Y, et al. (2012) Dysregulation of macrophage-secreted cathepsin B contributes to HIV-1-linked neuronal apoptosis. PLoS ONE 7: e36571. PMCID: PMC3365072