Hendrik Wesseling

Hendrik Wesseling
Merck & Co. | MSD

MSc, PhD cantab
Mass spectrometry, Single-Cell Proteomics, Neurobiology, Immunology, and Oncology

About

50
Publications
3,532
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
580
Citations
Additional affiliations
May 2015 - July 2019
Harvard Medical School
Position
  • PostDoc Position
October 2014 - April 2015
University of Cambridge
Position
  • Research Associate
Education
October 2010 - September 2014

Publications

Publications (50)
Article
Full-text available
Deletions on chromosome 22q11.2 are a strong genetic risk factor for development of schizophrenia and cognitive dysfunction. We employed shotgun liquid chromatography-mass spectrometry (LC-MS) proteomic and metabonomic profiling approaches on prefrontal cortex (PFC) and hippocampal (HPC) tissue from Df(16)A(+/-) mice, a model of the 22q11.2 deletio...
Article
Full-text available
The role of Arc in synaptic plasticity and memory consolidation has been investigated for many years with recent evidence that defects in the expression or activity of this immediate early gene may also contribute to the pathophysiology of brain disorders including schizophrenia and fragile X syndrome. These results bring forward the concept that r...
Preprint
Full-text available
Translation canonically begins at a single AUG and terminates at the stop codon, generating one protein species per transcript. However, some transcripts may use alternative initiation sites or sustain translation past their stop codon, generating multiple protein isoforms. Through other mechanisms such as alternative splicing, both neurons and gli...
Article
To elucidate the role of Tau isoforms and post-translational modification (PTM) stoichiometry in Alzheimer’s disease (AD), we generated a high-resolution quantitative proteomics map of 95 PTMs on multiple isoforms of Tau isolated from postmortem human tissue from 49 AD and 42 control subjects. Although Tau PTM maps reveal heterogeneity across subje...
Article
Full-text available
Current schizophrenia (SCZ) treatments fail to treat the broad range of manifestations associated with this devastating disorder. Thus, new translational models that reproduce the core pathological features are urgently needed to facilitate novel drug discovery efforts. Here, we report findings from the first comprehensive label-free liquid-mass sp...
Article
Activity-regulated cytoskeleton-associated protein (Arc) is an immediate early gene product that support neuroplastic changes important for cognitive function and memory formation. As a protein with homology to the retroviral Gag protein, a particular characteristic of Arc is its capacity to self-assemble into virus-like capsids that can package mR...
Preprint
Full-text available
Activity-regulated cytoskeleton-associated protein (Arc) is an immediate-early gene product that support neuroplastic changes important for cognitive function and memory formation. As a protein with homology to the retroviral Gag protein, a particular characteristic of Arc is its capacity to self-assemble into virus-like capsids that can package mR...
Article
Full-text available
Alternative translation initiation and stop codon readthrough in a few well-studied cases have been shown to allow the same transcript to generate multiple protein variants. Because the brain shows a particularly abundant use of alternative splicing, we sought to study alternative translation in CNS cells. We show that alternative translation is wi...
Article
Full-text available
Background Tuberous sclerosis complex (TSC) is a rare monogenic disorder characterized by benign tumors in multiple organs as well as a high prevalence of epilepsy, intellectual disability and autism. TSC is caused by inactivating mutations in the TSC1 or TSC2 genes. Heterozygocity induces hyperactivation of mTOR which can be inhibited by mTOR inhi...
Article
Rodent models of schizophrenia (SCZ) are indispensable when screening for novel treatments, but quantifying their translational relevance with the underlying human pathophysiology has proved difficult. A novel systems methodology (shown in Figure 1) was developed integrating and comparing proteomic data of anterior prefrontal cortex tissue from SCZ...
Article
\textit{Objectives:}$ Rodent models of major depressive disorder (MDD) are indispensable when screening for novel treatments, but assessing their translational relevance with human brain pathology has proved difficult. $\textit{Methods:}$ Using a novel systems approach, proteomics data obtained from post-mortem MDD anterior prefrontal cortex tissue...
Article
Objectives: Rodent models of major depressive disorder (MDD) are indispensable when screening for novel treatments, but assessing their translational relevance with human brain pathology has proved difficult. Methods: Using a novel systems approach, proteomics data obtained from post-mortem MDD anterior prefrontal cortex tissue (n =12) and match...
Article
Pharmacological and genetic rodent models of schizophrenia play an important role in the drug discovery pipeline, but quantifying the molecular similarity of such models with the underlying human pathophysiology has proved difficult. We developed a novel systems biology methodology for the direct comparison of anterior prefrontal cortex tissue from...
Article
Schizophrenia is a neuropsychiatric disorder affecting 1% of the world's population. Due to a broad range of symptoms and disease heterogeneity, current therapeutic approaches to treat schizophrenia fail to address all symptomatic manifestations of the disease. Therefore, disease models that reproduce core pathological features of schizophrenia are...
Article
Full-text available
Previous studies have shown that blood serum phosphoproteins are altered in schizophrenia patients in comparison to controls. However, it is not known whether phosphoproteins are also changed in response to treatment with antipsychotics. Blood samples were taken from patients (n=23) at baseline and after 6 weeks of olanzapine treatment. Immobilised...
Article
There is substantial interest in the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine in psychiatric research, as it exerts psychotomimetic and antidepressant effects in rodents and humans. Here we investigated proteomic changes in brain and serum after acute treatment of rats with ketamine using two targeted proteomic profiling methods. Mu...
Article
Full-text available
Background: Extensive research efforts have generated genomic, transcriptomic, proteomic, and functional data hoping to elucidate psychiatric pathophysiology. Selected reaction monitoring, a recently developed targeted proteomic mass spectrometric approach, has made it possible to evaluate previous findings and hypotheses with high sensitivity, rep...
Article
Full-text available
Although genetic studies suggest an overlap in risk alleles across the major psychiatric disorders, disease signatures reflecting overlapping symptoms have not been found. Profiling studies have identified candidate protein markers associated with specific disorders of the psychoaffective spectrum, but this has always been done in a selective fashi...
Article
Full-text available
Background Over the last decade, the transgenic N-methyl-D-aspartate receptor (NMDAR) NR1-knockdown mouse (NR1neo−/−) has been investigated as a glutamate hypofunction model for schizophrenia. Recent research has now revealed that the model also recapitulates cognitive and negative symptoms in the continuum of other psychiatric diseases, particular...
Article
Full-text available
Proteomic studies have increased our understanding of the molecular pathways affected in psychiatric disorders. Mass spectrometry and two-dimensional gel electrophoresis analyses of post-mortem brain samples from psychiatric patients have revealed effects on synaptic, cytoskeletal, antioxidant and mitochondrial protein networks. Multiplex immunoass...
Article
See Chapter 8 in the above book Modeling neuropsychiatric disorders in animals poses a significant challenge due to the subjective nature of diverse often overlapping symptoms, lack of objective biomarkers and diagnostics, and the rudimentary understanding of the pathophysiology. Successful translational research requires animal models that can in...
Article
Full-text available
Corynebacterium glutamicum accumulates up to 300 mM of inorganic polyphosphate (PolyP) in the cytosol or in granules. The gene products of cg0488 (ppx1) and cg1115 (ppx2) were shown to be active as exopolyphosphatases (PPX), as overexpression of either gene resulted in higher exopolyphosphatase activities in crude extracts and deletion of either ge...

Network

Cited By