Harry Whitwell

Harry Whitwell
Imperial College London | Imperial · Department of Metabolism

BSc(Hons), MSc, PhD

About

31
Publications
6,874
Reads
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494
Citations
Citations since 2016
28 Research Items
490 Citations
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2016201720182019202020212022050100150
2016201720182019202020212022050100150
Introduction
Harry Whitwell currently works as proteomics lead at the National Phenome Centre and Division of Systems Medicine at Imperial College London. Harry does research in cell Biology and Biotechnology.
Additional affiliations
June 2020 - present
Imperial College London
Position
  • Proteomics Lead
May 2017 - June 2020
Imperial College London
Position
  • PostDoc Position
Description
  • Exploiting chemical labelling to identify methylated protein substrates by mass spectrometry. The research focuses on DOT1L and is funded by CRUK.
August 2015 - May 2017
UCL
Position
  • PostDoc Position

Publications

Publications (31)
Article
Full-text available
Pulmonary arterial hypertension (PAH) is an unmet clinical need. The lack of models of human disease is a key obstacle to drug development. We present a biomimetic model of pulmonary arterial endothelial-smooth muscle cell interactions in PAH, combining natural and induced bone morphogenetic protein receptor 2 (BMPR2) dysfunction with hypoxia to in...
Article
Objectives: Peptide tyrosine tyrosine (PYY) exists as two species, PYY<sub>1-36</sub> and PYY<sub>3-36</sub> <sup>,</sup> with distinct effects on insulin secretion and appetite regulation. The detailed effects of bariatric surgery on PYY<sub>1-36</sub> and PYY<sub>3-36</sub> secretion are not known as previous studies have used non-specific immun...
Article
Mitochondrial fission and a metabolic switch from oxidative phosphorylation to glycolysis are key features of vascular pathology in pulmonary arterial hypertension (PAH) and are associated with exuberant endothelial proliferation and apoptosis. The underlying mechanisms are poorly understood. We describe the contribution of two intracellular chlori...
Article
Full-text available
Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Additional tools are also ne...
Preprint
Full-text available
Earlier detection of pancreatic ductal adenocarcinoma (PDAC) is key to improving patient outcomes, as it is mostly detected at advanced stages which are associated with poor survival. Developing non-invasive blood tests for early detection would be an important breakthrough. The primary objective of the work presented here was to use a unique datas...
Article
Full-text available
Parenclitic networks provide a powerful and relatively new way to coerce multidimensional data into a graph form, enabling the application of graph theory to evaluate features. Different algorithms have been published for constructing parenclitic networks, leading to the question—which algorithm should be chosen? Initially, it was suggested to calc...
Preprint
Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Comprehensively capturing th...
Article
Full-text available
COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma prot...
Article
Full-text available
COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma prot...
Article
Full-text available
Investigation of human mitochondrial (mt) genome variation has been shown to provide insights to the human history and natural selection. By analyzing 24,167 human mt-genome samples, collected for five continents, we have developed a co-mutation network model to investigate characteristic human evolutionary patterns. The analysis highlighted richer...
Article
Protein methylation is a key post-translational modification whose effects on gene expression have been intensively studied over the last two decades. Recently, renewed interest in non-histone protein methylation has gained momentum for its role in regulating important cellular processes and the activity of many proteins, including transcription fa...
Preprint
Full-text available
COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. There is an urgent need for predictive markers that can guide clinical decision-making, inform about the effect of experimental therapies, and point to novel therapeutic targets. Here, we characterize the time-dependent pr...
Article
Full-text available
Biological aging is a complex process involving multiple biological processes. These can be understood theoretically though considering them as individual networks—e.g., epigenetic networks, cell-cell networks (such as astroglial networks), and population genetics. Mathematical modeling allows the combination of such networks so that they may be st...
Article
Full-text available
Surfactant treatment for neonatal respiratory distress syndrome has dramatically improved survival of preterm infants. However, this has resulted in a markedly increased incidence of sequelae such as neonatal chronic inflammatory lung disease. The current surfactant preparations in clinical use lack the natural lung defence proteins surfactant prot...
Article
Full-text available
Ovarian cancer has a poor survival rate due to late diagnosis and improved methods are needed for its early detection. Our primary objective was to identify and incorporate additional biomarkers into longitudinal models to improve on the performance of CA125 as a first-line screening test for ovarian cancer. This case–control study nested within UK...
Article
Full-text available
Motivation: Database searching of isotopically labelled PTMs can be problematic and we frequently find that only one, or neither in a heavy/light pair are assigned. In such cases, having a pair of MS/MS spectra that differ due to an isotopic label can assist in identifying the relevant m/z values that support the correct peptide annotation or can...
Preprint
Full-text available
Studies of human mitochondrial (mt) genome variation may be undertaken to investigate the human history and natural selection. By analyzing nucleotide co-occurrence over the entire human mt-genome, we have developed a network model to describe human evolutionary patterns. Using 7,424 unique polymorphic sites, we found evidence that mutation biases...
Article
Full-text available
Prediction and diagnosis of complex disease may not always be possible with a small number of biomarkers. Modern 'omics' technologies make it possible to cheaply and quantitatively assay hundreds of molecules generating large amounts of data from individual samples. In this study, we describe a parenclitic network-based approach to disease classifi...
Article
Full-text available
The non-invasive differentiation of malignant and benign biliary disease is a clinical challenge. Carbohydrate antigen 19-9 (CA19-9), leucine-rich a2-glycoprotein (LRG1), interleukin 6 (IL6), pyruvate kinase M2 (PKM2), cytokeratin 19 fragment (CYFRA21.1) and mucin 5AC (MUC5AC) have reported utility for differentiating cholangiocarcinoma (CCA) from...
Article
Full-text available
S-nitrosation, commonly referred to as S-nitrosylation, is widely regarded as a ubiquitous, stable post-translational modification that directly regulates many proteins. Such a widespread role would appear to be incompatible with the inherent lability of the S-nitroso bond, especially its propensity to rapidly react with thiols to generate disulfid...
Article
Full-text available
Biomarkers for the early detection of pancreatic cancer are urgently needed. The aim of this pilot study was to evaluate changes in serum N-glycoproteins and their glycosylation status prior to clinical presentation of pancreatic cancer that may be potential biomarkers. Prediagnosis serum samples pooled according to five time-to-diagnosis groups an...
Article
Full-text available
The formation of protein coronas on nanoparticles (NP) has been investigated almost exclusively in serum, despite the prevailing route of exposure being inhalation of airborne particles. In addition, an increasing number of nanomedicines, that exploit the airways as the site of delivery, are undergoing medical trials. An understanding of the effect...
Thesis
Particles with a single dimension smaller than 100 nm are called nanoparticles (NPs). There is a large amount of epidemiology that anthropogenic particles cause increased mortality, increased risk of asthma and increased incidence of lung adenocarcinoma. Inhaled NPs can reach the lung terminus, interacting with a lipid lining at the air-liquid int...
Article
Full-text available
Pulmonary epithelial cell responses can enhance type 2 immunity and contribute to control of nematode infections. An important epithelial product is the collectin Surfactant Protein D (SP-D). We found that SP-D concentrations increased in the lung following Nippostrongylus brasiliensi infection; this increase was dependent on key components of the...
Article
Full-text available
Abstract The lung provides the main route for nanomaterial exposure. Surfactant protein A (SP-A) is an important respiratory innate immune molecule with the ability to bind or opsonise pathogens to enhance phagocytic removal from the airways. We hypothesised that SP-A, like surfactant protein D, may interact with inhaled nanoparticulates, and that...
Article
Full-text available
When biomolecules attach to engineered nanoparticle (ENP) surfaces, they confer the particles with a new biological identity. Physical format may also radically alter, changing ENP stability and agglomeration state within seconds. In order to measure which biomolecules are associated with early ENP growth, we studied ENPs in conditioned medium from...

Questions

Questions (2)
Question
I need to react some peptides with tri-nitrobenzene sulfonic acid (TNBS) which I am doing in sodium tetraborate buffer. I then need to remove any unreacted TNBS reagent before moving on to the next step. To do this, I've been using chloroform methanol ppt. When I do this, a precipitate forms at the interphase but after removing the aqueous layer, and adding methanol, the precipitate seems to re-dissolve. I didn't expect this! Has anyone any suggestions for otherways of removing TNBS? I have tried phase partitioning it in some chloroform, but it stays in the aqueous phase with the peptides (I assume because of the sulfonic acid).
Thanks!
Question
I am running blanks in positive mode on a HPLC-MS/MS  (LTQ-Orbitrap XL) system. I recently have replaced the injection needle and loop on the HPLC (Ultimate 3000) and have developed a contaminating peak at 469.28 m/z in positive mode which I have not seen before. I've been running blanks and standard to try and clear it, but it hasn't changed in intensity! Anyone have a clue as to what it is? I've attached a picture of the spectra. Thanks.

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