Jerry L. Nadler

12-Lipoxygenase (12-LOX) plays a key role in the hyperinflammatory response caused by SARS-CoV-2

Melinee D’silva, M Vaughan, David J. Maloney, Sachin A. Gupte et autres

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant global morbidity and mortality. The severe disease outcomes are often associated with a hyperinflammatory response known as a "cytokine storm." The mechanisms underlying this exaggerated immune response remain incompletely understood. …

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Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries

Alicia Huerta‐Chagoya, Joohyun Kim, Ravi Mandla, Yingchang Lu et autres

BACKGROUND: Polygenic risk scores (PRSs) improve prediction of the development of type 2 diabetes over the use of clinical risk factors alone; however, they perform poorly in populations of non-European ancestry, limiting their global clinical utility. We aimed to deliver comprehensive and …

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Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries

Alicia Huerta‐Chagoya, Joohyun Kim, Ravi Mandla, Yingchang Lu et autres

Background: Polygenic risk scores (PRSs) improve prediction of the development of type 2 diabetes over the use of clinical risk factors alone; however, they perform poorly in populations of non-European ancestry, limiting their global clinical utility. We aimed to deliver comprehensive and …

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12-Lipoxygenase Drives Hyperinflammatory Responses and Enhances COVID-19 Severity 9032

Chandra Shekhar Bakshi, Melinee D’silva, Jerry L. Nadler, Dave Meloney

Abstract Description The COVID-19 pandemic remains a significant global challenge, with comorbidities like obesity and diabetes exacerbating the severe outcomes. However, the mechanisms driving heightened susceptibility in these populations are poorly understood. SARS-CoV-2 infection disrupts lipid metabolism pathways regulated by Phospholipase A2 …

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OR34-04 Human Pancreatic Islet Immuno-Metabolism Response after Cytokine Administration

Melinee D’silva, Beata Małachowska, Yunping Qiu, Juan Manuel Sepúlveda-Sánchez et autres

Abstract Disclosure: M. D'silva: None. B. Malachowska: None. Y. Qiu: None. J. Sepulveda: None. R. Chang: None. S. Sidoli: None. J.L. Nadler: None. I.J. Kurland: Scorpion Therapeutics. An important early hallmark of Type I Diabetes Mellitus (T1D) is beta-cell dysfunction, a critical …

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Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits

Lynne E. Wagenknecht, Tin Louie, Christopher A. Haiman, Carolina G Downie et autres

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Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits

Lauren E. Petty, Hung‐Hsin Chen, Eitan Frankel, Wanying Zhu et autres

Here, we present a multi-omics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits conducted to date in Hispanic/Latino populations (nmax = 63,184). We conduct a meta-analysis of 16 type 2 diabetes and 19 lipid trait GWAS, identifying 20 …

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12-Lipoxygenase Inhibition Improves Glycemia and Obesity-associated Inflammation in Male Human Gene Replacement Mice

Kerim B. Kaylan, Titli Nargis, Kayla Figatner, Jiayi Wang et autres

Obesity-associated inflammation is characterized by macrophage infiltration into peripheral tissues, contributing to the progression of prediabetes and type 2 diabetes. 12-lipoxygenase (12-LOX) catalyzes the formation of pro-inflammatory eicosanoids and promotes the migration of macrophages, yet its role in obesity-associated inflammation remains incompletely …

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Joint analysis of the nPOD-Virus Group data: the association of enterovirus with type 1 diabetes is supported by multiple markers of infection in pancreas tissue

Sarah J. Richardson, Teresa Rodríguez-Calvo, Jutta E. Laiho, John S. Kaddis et autres

Abstract Aims/hypothesis Previous pathology studies have associated enterovirus infections with type 1 diabetes by examining the enterovirus capsid protein 1 (VP1) in autopsy pancreases obtained near diabetes diagnosis. The Network for Pancreatic Organ Donors with Diabetes (nPOD) has since obtained pancreases from …

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12-Lipoxygenase inhibition improves glucose homeostasis and obesity-associated inflammation in human gene replacement mice

Kerim B. Kaylan, Titli Nargis, Kayla Figatner, Jiayi Wang et autres

ABSTRACT Obesity-associated inflammation is characterized by macrophage infiltration into peripheral tissues, contributing to the progression of prediabetes and type 2 diabetes (T2D). The enzyme 12-lipoxygenase (12-LOX) catalyzes the formation of pro-inflammatory eicosanoids and is known to promote the migration of macrophages, yet …

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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

Victor Lim, Donald W. Bowden, Ko Willems van Dijk, Lars Lind et autres

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12-Lipoxygenase inhibition delays onset of autoimmune diabetes in human gene replacement mice

Titli Nargis, Charanya Muralidharan, Jacob R. Enriquez, Jiayi E. Wang et autres

Type 1 diabetes (T1D) is characterized by the autoimmune destruction of insulin-producing β cells and involves an interplay between β cells and cells of the innate and adaptive immune systems. We investigated the therapeutic potential of targeting 12-lipoxygenase (12-LOX), an enzyme implicated …

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