Peter J. McGuire
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Cytochrome c oxidase dependent respiration is essential for T cell activation, proliferation and memory formation Open
T cell activation requires extensive metabolic reprogramming, but the specific requirement for mitochondrial respiration (MR) remains unresolved. While most studies have focused on aerobic glycolysis as the primary driver of proliferation …
Mitochondrial dysfunction enhances influenza pathogenesis by up-regulating de novo sialic acid biosynthesis Open
Mitochondrial dysfunction can trigger metabolic adaptations that resemble those induced by influenza A virus (IAV) infection. Here, we show that oxidative phosphorylation (OXPHOS) impairment, modeled by Ndufs4 deficiency, reprograms lung e…
Tipping the balance: innate and adaptive immunity in mitochondrial disease Open
Mitochondrial diseases (MtD) provide a unique window into the complex interplay between metabolism and immune function. These rare disorders, caused by defects in oxidative phosphorylation, result in bioenergetic deficiencies that disrupt …
Cytochrome c oxidase dependent respiration is essential for T cell activation, proliferation and memory formation Open
T cell activation, proliferation, and differentiation are fundamentally driven by shifts in cellular metabolism, with mitochondria playing a central role. Cytochrome c oxidase (COX, complex IV) is a key player in this process, as its activ…
Single-cell mapping of metabolic dependences using ATP as a biomarker Open
Metabolic dependences highlight a cell's reliance on specific pathways to meet its bioenergetic needs, with these pathways being interrogated using chemical inhibitors to assess their significance. While surrogate markers of bioenergetics …
Caspase-11 drives macrophage hyperinflammation in models of Polg-related mitochondrial disease Open
Mitochondrial diseases (MtD) represent a significant public health challenge due to their heterogenous clinical presentation, often severe and progressive symptoms, and lack of effective therapies. Environmental exposures, such bacterial a…
View article: Primary oxidative phosphorylation defects lead to perturbations in the human B cell repertoire
Primary oxidative phosphorylation defects lead to perturbations in the human B cell repertoire Open
Introduction The majority of studies on oxidative phosphorylation in immune cells have been performed in mouse models, necessitating human translation. To understand the impact of oxidative phosphorylation (OXPHOS) deficiency on human immu…
Inflammatory and interferon gene expression signatures in patients with mitochondrial disease Open
Background People with mitochondrial disease (MtD) are susceptible to metabolic decompensation and neurological symptom progression in response to an infection. Increasing evidence suggests that mitochondrial dysfunction may cause chronic …
View article: Pyruvate dehydrogenase complex integrates the metabolome and epigenome in CD8+ memory T cell differentiation in vitro
Pyruvate dehydrogenase complex integrates the metabolome and epigenome in CD8+ memory T cell differentiation in vitro Open
Modulation of metabolic flux through pyruvate dehydrogenase complex (PDC) plays an important role in T cell activation and differentiation. PDC sits at the transition between glycolysis and the tricarboxylic acid cycle and is a major produ…
PI3Kdelta coordinates transcriptional, epigenetic and metabolic changes to promote effector CD8 T cells differentiation Open
Activated PI3K-delta syndrome (APDS) is a primary immunodeficiency caused by heterozygous activating mutations of PIK3CD, resulting in dysregulated immunity, recurrent infections and lymphoproliferation, yet underlying mechanisms behind th…
Epitope-level profiling in children with mitochondrial disease reveals limitations in the antibacterial antibody repertoire Open
Overall, the antibacterial humoral response is distinctive in children with MtD, suggesting an important role for OXPHOS in B cell function.
Inflammatory and interferon gene expression signatures in patients with mitochondrial disease Open
Background: People with mitochondrial disease (MtD) are susceptible to metabolic decompensation and neurological symptom progression in response to an infection. Increasing evidence suggests that mitochondrial dysfunction may cause chronic…
View article: Pyruvate dehydrogenase complex integrates the metabolome and epigenome in memory T cell differentiation in vitro
Pyruvate dehydrogenase complex integrates the metabolome and epigenome in memory T cell differentiation in vitro Open
Background Modulation of metabolic flux through pyruvate dehydrogenase complex (PDC) plays an important role in T cell activation and differentiation. PDC sits at the transition between glycolysis and the tricarboxylic acid cycle and is a …
Additional file 4 of Inflammatory and interferon gene expression signatures in patients with mitochondrial disease Open
Additional file 4: Table S3. GSEA results using BTM terms.
Additional file 3 of Inflammatory and interferon gene expression signatures in patients with mitochondrial disease Open
Additional file 3: Table S2. GSEA results using GO terms.
Additional file 2 of Inflammatory and interferon gene expression signatures in patients with mitochondrial disease Open
Additional file 2: Table S1. Differential gene expression results from DESeq2.
Multiparameter stimulation mapping of signaling states in single pediatric immune cells reveals heightened tonic activation during puberty Open
Cellular stimulation via factors such as cytokines followed by multiparameter single-cell measurements is a powerful approach to interrogate cellular functions. However, transforming such high-dimensional data into biological insights pres…
View article: Comprehensive profiling of the human viral exposome in households containing an at‐risk child with mitochondrial disease during the 2020–2021 COVID‐19 pandemic
Comprehensive profiling of the human viral exposome in households containing an at‐risk child with mitochondrial disease during the 2020–2021 COVID‐19 pandemic Open
Background Viral infection is a major cause of morbidity in children with mitochondrial disease (MtD). As a result, families with children with MtD are highly adherent to risk mitigation behaviours (RMBs) advised by the Centers for Disease…
Pyruvate dehydrogenase is dispensable for T cell function in vivo Open
Interrupting a major pathway in intermediary metabolism leads to an accumulation of substrates and upstream metabolites, downstream product deficiency, changes in feedback inhibition or activation, and diversion to alternative pathways. Al…
View article: IFNγ regulates NAD+ metabolism to promote the respiratory burst in human monocytes
IFNγ regulates NAD+ metabolism to promote the respiratory burst in human monocytes Open
Interferon γ (IFNγ) is an essential and pleiotropic activator of human monocytes, but little is known about the changes in cellular metabolism required for IFNγ-induced activation. We sought to elucidate the mechanisms by which IFNγ reprog…
Undiagnosed COVID-19 in households with a child with mitochondrial disease Open
Background The impact of the COVID-19 pandemic on medically fragile populations, who are at higher risk of severe illness and sequelae, has not been well characterized. Viral infection is a major cause of morbidity in children with mitocho…