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rabindra.tharu.np@gmail.com
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Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains
Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, and recent evidence suggests that pathogenesis may be in part mediated by inflammatory processes, the molecular and cellular architectures of which are largely unknown. To identify and characterize selectively vulnerable brain cell populations in PD, we performed single-nucleus transcriptomics and unbiased proteomics to profile the prefrontal cortex…
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rabindra.tharu.np@gmail.com
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Human OX40L-CAR-T(regs) target activated antigen-presenting cells and control T cell alloreactivity
Regulatory T cells (T) make major contributions to immune homeostasis. Because T dysfunction can lead to both allo- and autoimmunity, there is interest in correcting these disorders through T adoptive transfer. Two of the central challenges in clinically deploying T cellular therapies are ensuring phenotypic stability and maximizing potency. Here, we describe an approach to…
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rabindra.tharu.np@gmail.com
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Neutrophil extracellular traps protect the kidney from ascending infection and are required for a positive leukocyte dipstick test
Lower urinary tract infection (UTI) is common but only rarely complicated by pyelonephritis. However, the mechanisms preventing extension to the kidney are unclear. Here, we identified neutrophil extracellular traps (NETs) in healthy human urine that provide an antibacterial defense strategy within the urinary tract. In both in vivo murine models of UTI where uropathogenic are…
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rabindra.tharu.np@gmail.com
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A spatially resolved single-cell lung atlas integrated with clinical and blood signatures distinguishes COVID-19 disease trajectories
COVID-19 is characterized by a broad range of symptoms and disease trajectories. Understanding the correlation between clinical biomarkers and lung pathology during acute COVID-19 is necessary to understand its diverse pathogenesis and inform more effective treatments. Here, we present an integrated analysis of longitudinal clinical parameters, peripheral blood markers, and lung pathology in 142 Brazilian…
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rabindra.tharu.np@gmail.com
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Nanoparticle delivery of innate immune agonists combined with senescence-inducing agents promotes T cell control of pancreatic cancer
Pancreatic ductal adenocarcinoma (PDAC) has quickly risen to become the third leading cause of cancer-related death in the United States. This is in part because of its fibrotic tumor microenvironment (TME) that contributes to poor vascularization and immune infiltration and subsequent chemo- and immunotherapy failure. Here, we investigated an immunotherapy approach combining delivery of stimulator…
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rabindra.tharu.np@gmail.com
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Repeated Omicron exposures redirect SARS-CoV-2-specific memory B cell evolution toward the latest variants
Immunological imprinting by ancestral SARS-CoV-2 strains is thought to impede the robust induction of Omicron-specific humoral responses by Omicron-based booster vaccines. Here, we analyzed the specificity and neutralization activity of memory B (B) cells after repeated BA.5 exposure in individuals previously imprinted by ancestral strain-based mRNA vaccines. After a second BA.5 exposure, B cells with…
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rabindra.tharu.np@gmail.com
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Targeting the transferrin receptor to transport antisense oligonucleotides across the mammalian blood-brain barrier
Antisense oligonucleotides (ASOs) are promising therapeutics for treating various neurological disorders. However, ASOs are unable to readily cross the mammalian blood-brain barrier (BBB) and therefore need to be delivered intrathecally to the central nervous system (CNS). Here, we engineered a human transferrin receptor 1 (TfR1) binding molecule, the oligonucleotide transport vehicle (OTV), to transport a…
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rabindra.tharu.np@gmail.com
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Natural killer cells promote neutrophil extracellular traps and restrain macular degeneration in mice
Neovascular age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Although it is known that nvAMD is associated with focal inflammation, understanding of the precise immune components governing this process remains limited. Here, we identified natural killer (NK) cells as a prominent lymphocyte population infiltrating the perivascular space of choroidal…
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rabindra.tharu.np@gmail.com
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Acyl-CoA binding protein for the experimental treatment of anorexia
Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced…
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rabindra.tharu.np@gmail.com
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Adjuvantation of a SARS-CoV-2 mRNA vaccine with controlled tissue-specific expression of an mRNA encoding IL-12p70
Messenger RNA (mRNA) vaccines were pivotal in reducing severe acute respiratory syndrome 2 (SARS-CoV-2) infection burden, yet they have not demonstrated robust durability, especially in older adults. Here, we describe a molecular adjuvant comprising a lipid nanoparticle (LNP)-encapsulated mRNA encoding interleukin-12p70 (IL-12p70). The bioactive adjuvant was engineered with a multiorgan protection (MOP) sequence to restrict…
