Katie L. Burnham
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View article: Pediatric Critical Illness Endotypes Reveal Distinct Outcomes and Immune Pathways Shared Across Cause of Illness
Pediatric Critical Illness Endotypes Reveal Distinct Outcomes and Immune Pathways Shared Across Cause of Illness Open
View article: Evidence for enhancer activity in intron 1 of TNFRSF1A using CRISPR/Cas9 in human induced pluripotent stem cell-derived macrophages
Evidence for enhancer activity in intron 1 of TNFRSF1A using CRISPR/Cas9 in human induced pluripotent stem cell-derived macrophages Open
View article: Trans-eQTL mapping prioritises USP18 as a negative regulator of interferon response at a lupus risk locus
Trans-eQTL mapping prioritises USP18 as a negative regulator of interferon response at a lupus risk locus Open
Although genome-wide association studies have provided valuable insights into the genetic basis of complex traits and diseases, translating these findings to causal genes and their downstream mechanisms remains challenging. We performed tr…
View article: A consensus blood transcriptomic framework for sepsis
A consensus blood transcriptomic framework for sepsis Open
Sepsis is a life-threatening condition driven by a maladaptive host response to infection. To establish a standardized blood transcriptomic subtype model, we aggregated blood transcriptomics data from two major sepsis cohorts: the Molecula…
View article: Single-cell level characterization of B cell depletion and repopulation following rituximab in systemic lupus erythematosus
Single-cell level characterization of B cell depletion and repopulation following rituximab in systemic lupus erythematosus Open
Objective Rituximab, a CD20 + B cell depletion therapy, is frequently used in the treatment of systemic lupus erythematosus (SLE). However, variability in patient response highlights the need for a deeper understanding of the underlying im…
View article: Context-specific regulatory genetic variation in MTOR dampens neutrophil-T cell crosstalk in sepsis, modulating disease
Context-specific regulatory genetic variation in MTOR dampens neutrophil-T cell crosstalk in sepsis, modulating disease Open
Sepsis is a heterogeneous clinical syndrome with a high mortality rate and personalised stratification strategies are proposed as essential to successful targeted therapeutics. Here, we characterise genetic variation that modulates MTOR, a…
View article: The contribution of genetic determinants of blood gene expression and splicing to molecular phenotypes and health outcomes
The contribution of genetic determinants of blood gene expression and splicing to molecular phenotypes and health outcomes Open
The biological mechanisms through which most nonprotein-coding genetic variants affect disease risk are unknown. To investigate gene-regulatory mechanisms, we mapped blood gene expression and splicing quantitative trait loci (QTLs) through…
View article: Host Gene Expression Prior to Emergency Paediatric Intensive Care Admission Predicts Severity and Shared Immune Dysfunction in an Inclusive Population of Critically Ill Children
Host Gene Expression Prior to Emergency Paediatric Intensive Care Admission Predicts Severity and Shared Immune Dysfunction in an Inclusive Population of Critically Ill Children Open
View article: Causal inference can lead us to modifiable mechanisms and informative archetypes in sepsis
Causal inference can lead us to modifiable mechanisms and informative archetypes in sepsis Open
View article: Integrating Natural and Engineered Genetic Variation to Decode Regulatory Influence on Blood Traits
Integrating Natural and Engineered Genetic Variation to Decode Regulatory Influence on Blood Traits Open
Understanding the function of genetic variants associated with human traits and diseases remains a significant challenge. Here we combined analyses based on natural genetic variation and genetic engineering to dissect the function of 94 no…
View article: Misexpression of inactive genes in whole blood is associated with nearby rare structural variants
Misexpression of inactive genes in whole blood is associated with nearby rare structural variants Open
Gene misexpression is the aberrant transcription of a gene in a context where it is usually inactive. Despite its known pathological consequences in specific rare diseases, we have a limited understanding of its wider prevalence and mechan…
View article: eQTLs identify regulatory networks and drivers of variation in the individual response to sepsis
eQTLs identify regulatory networks and drivers of variation in the individual response to sepsis Open
View article: High-throughput mass spectrometry maps the sepsis plasma proteome and differences in patient response
High-throughput mass spectrometry maps the sepsis plasma proteome and differences in patient response Open
Sepsis, the dysregulated host response to infection causing life-threatening organ dysfunction, is a global health challenge requiring better understanding of pathophysiology and new therapeutic approaches. Here, we applied high-throughput…
View article: Patient stratification using plasma cytokines and their regulators in sepsis: relationship to outcomes, treatment effect and leucocyte transcriptomic subphenotypes
Patient stratification using plasma cytokines and their regulators in sepsis: relationship to outcomes, treatment effect and leucocyte transcriptomic subphenotypes Open
Rationale Heterogeneity of the host response within sepsis, acute respiratory distress syndrome (ARDS) and more widely critical illness, limits discovery and targeting of immunomodulatory therapies. Clustering approaches using clinical and…
View article: Supplementary_Tables.zip
Supplementary_Tables.zip Open
Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection, for which disease heterogeneity is a major obstacle to developing targeted treatments. We have previously identified gene e…
View article: Genetic determinants of blood gene expression and splicing and their contribution to molecular phenotypes and health outcomes
Genetic determinants of blood gene expression and splicing and their contribution to molecular phenotypes and health outcomes Open
Summary The biological mechanisms through which most non-protein-coding genetic variants affect disease risk are unknown. To investigate the gene-regulatory cascades that ensue from these variants, we mapped blood gene expression and splic…
View article: Misexpression of inactive genes in whole blood is associated with nearby rare structural variants
Misexpression of inactive genes in whole blood is associated with nearby rare structural variants Open
Gene misexpression is the aberrant transcription of a gene in a context where it is usually inactive. Despite its known pathological consequences in specific rare diseases, we have a limited understanding of its wider prevalence and mechan…
View article: eQTLs identify regulatory networks and drivers of variation in the individual response to sepsis
eQTLs identify regulatory networks and drivers of variation in the individual response to sepsis Open
Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection, for which disease heterogeneity is a major obstacle to developing targeted treatments. We have previously identified gene e…
View article: A Transcriptomic Approach to Understand Patient Susceptibility to Pneumonia After Abdominal Surgery
A Transcriptomic Approach to Understand Patient Susceptibility to Pneumonia After Abdominal Surgery Open
Objective: To describe immune pathways and gene networks altered following major abdominal surgery and to identify transcriptomic patterns associated with postoperative pneumonia. Background: Nosocomial infections are a major healthcare ch…
View article: Neutrophil and emergency granulopoietic drivers of sepsis immune suppression and an extreme response to infection
Neutrophil and emergency granulopoietic drivers of sepsis immune suppression and an extreme response to infection Open
The dysregulated host response to infection leading to organ dysfunction is highly heterogeneous. It is currently poorly delineated by sepsis as a clinical syndromic classification, thus confounding immunotherapy trials. Here we establish …
View article: Neutrophil and emergency granulopoietic drivers of sepsis immune suppression and an extreme response to infection
Neutrophil and emergency granulopoietic drivers of sepsis immune suppression and an extreme response to infection Open
The dysregulated host response to infection leading to organ dysfunction is highly heterogeneous. It is currently poorly delineated by sepsis as a clinical syndromic classification, thus confounding immunotherapy trials. Here we establish …
View article: Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis
Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis Open
Sepsis arises from diverse and incompletely understood dysregulated host response processes following infection that leads to life-threatening organ dysfunction. Here we showed that neutrophils and emergency granulopoiesis drove a maladapt…
View article: Neutrophil and emergency granulopoietic drivers of sepsis immune suppression and an extreme response to infection
Neutrophil and emergency granulopoietic drivers of sepsis immune suppression and an extreme response to infection Open
The dysregulated host response to infection leading to organ dysfunction is highly heterogeneous. It is currently poorly delineated by sepsis as a clinical syndromic classification, thus confounding immunotherapy trials. Here we establish …
View article: A transcriptomic approach to understand patient susceptibility to pneumonia after abdominal surgery
A transcriptomic approach to understand patient susceptibility to pneumonia after abdominal surgery Open
Rationale Nosocomial infections are a major healthcare challenge, developing in over 20% of patients aged 45 or over undergoing major-abdominal surgery, with postoperative pneumonia associated with an almost five-fold increase in 30-day mo…
View article: Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19
Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19 Open
View article: COMBATdb: a database for the COVID-19 Multi-Omics Blood ATlas
COMBATdb: a database for the COVID-19 Multi-Omics Blood ATlas Open
Advances in our understanding of the nature of the immune response to SARS-CoV-2 infection, and how this varies within and between individuals, is important in efforts to develop targeted therapies and precision medicine approaches. Here w…
View article: An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression
An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression Open
Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investiga…
View article: Constructing custom-made radiotranscriptomic signatures from CT angiograms: an application in COVID-19 vascular inflammation
Constructing custom-made radiotranscriptomic signatures from CT angiograms: an application in COVID-19 vascular inflammation Open
Background Advances in computational methodologies have enabled processing of large datasets originating from imaging studies. However, most imaging biomarkers suffer from a lack of direct links with underlying biology, as they are only ob…
View article: Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19
Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19 Open
View article: High-throughput mass spectrometry maps the sepsis plasma proteome and differences in response
High-throughput mass spectrometry maps the sepsis plasma proteome and differences in response Open
Summary Sepsis, the dysregulated host response to infection causing life-threatening organ dysfunction, is an unmet global health challenge. Here we apply high-throughput tandem mass spectrometry to delineate the plasma proteome for sepsis…