Filippo Prischi

Filippo Prischi
University of Essex · School of Life Sciences

PhD

About

44
Publications
13,865
Reads
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1,181
Citations
Citations since 2017
21 Research Items
708 Citations
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2017201820192020202120222023050100150
Introduction
I am a Group Leader and Senior Lecturer (Associate Professor) in Biochemistry at University of Essex. My main research interest is the characterisation of protein complexes that are part of signalling pathways, in normal and cancer cells. My goal is to understand how the molecular machines that compose signalling pathways work together to transfer information. My group is generously supported by the University of Essex, The Leverhulme Trust and The Wellcome Trust. https://filippoprischilab.org/
Additional affiliations
June 2015 - present
University of Essex
Position
  • Lecturer
Description
  • BS131: Biochemistry of Macromolecules
June 2015 - present
University of Essex
Position
  • Lecturer
May 2010 - May 2015
Imperial College London
Position
  • Research Associate
Education
October 2005 - November 2009
MRC National Institute for Medical Research and Università degli Studi di Siena
Field of study
September 2003 - September 2005
Università degli Studi di Siena
Field of study
  • Molecular and Cellular Biology
September 2000 - November 2003
Università degli Studi di Siena
Field of study
  • Biological Sciences

Publications

Publications (44)
Article
Full-text available
Lung and bladder cancers are mostly incurable because of the early development of drug resistance and metastatic dissemination. Hence, improved therapies that tackle these two processes are urgently needed to improve clinical outcome. We have identified RSK4 as a promoter of drug resistance and metastasis in lung and bladder cancer cells. Silencing...
Article
Full-text available
The interaction between macromolecular proteins and small molecule ligands is an essential component of cellular function. Such ligands may include enzyme substrates, molecules involved in cellular signalling or pharmaceutical drugs. Together with biophysical techniques used to assess the thermodynamic and kinetic properties of ligand binding to pr...
Article
Full-text available
Blocking the signaling activated by the plasma membrane receptor CD93 has recently been demonstrated a useful tool in antiangiogenic treatment and oncotherapy. In the proliferating endothelium, CD93 regulates cell adhesion, migration, and vascular maturation, yet it is unclear how CD93 interacts with the extracellular matrix activating signaling pa...
Article
Alkaptonuria (AKU) is an ultra-rare genetic disease caused by a deficient activity of the enzyme homogentisate 1,2-dioxygenase (HGD) leading to the accumulation of homogentisic acid (HGA) on connective tissues. Even though AKU is a multi-systemic disease, osteaoarticular cartilage is the most affected system and the most damaged tissue by the disea...
Article
Full-text available
Prostate cancer (PCa) is the second most commonly occurring cancer in men, with over a million new cases every year worldwide. Tumor growth and disease progression is mainly dependent on the Androgen Receptor (AR), a ligand dependent transcription factor. Standard PCa therapeutic treatments include androgen-deprivation therapy and AR signaling inhi...
Article
Full-text available
The p70 ribosomal S6 kinase (S6K) family is a group of highly conserved kinases in eukaryotes that regulates cell growth, cell proliferation, and stress response via modulating protein synthesis and ribosomal biogenesis. S6Ks are downstream effectors of the Target of Rapamycin (TOR) pathway, which connects nutrient and energy signaling to growth an...
Article
Full-text available
The recent outbreak of the respiratory syndrome-related coronavirus (SARS-CoV-2) is stimulating an unprecedented scientific campaign to alleviate the burden of the coronavirus disease (COVID-19). One line of research has focused on targeting SARS-CoV-2 proteins fundamental for its replication by repurposing drugs approved for other diseases. The fi...
Article
Full-text available
Background: Alkaptonuria (AKU) is an ultra-rare autosomal recessive disease caused by a mutation in the homogentisate 1,2-dioxygenase (HGD) gene. One of the main obstacles in studying AKU, and other ultra-rare diseases, is the lack of a standardized methodology to assess disease severity or response to treatment. Quality of Life scores (QoL) are a...
Article
Full-text available
SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 26th July 2020, has infected over 16 million people. Despite the urgent need to find effective therapeutics, research on SARS-CoV-2 has been affected by a lack of suitable animal models. To facilitate the deve...
Preprint
Full-text available
The recent outbreak of the respiratory syndrome-related coronavirus (SARS-CoV-2) is stimulating an unprecedented scientific campaign to alleviate the burden of the coronavirus disease (COVID-19). One line of research has focused on targeting SARS-CoV-2 proteins fundamental for its replication by repurposing drugs approved for other diseases. The fi...
Article
Full-text available
The Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The virus has rapidly spread in humans, causing the ongoing Coronavirus pandemic. Recent studies have shown that, similarly to SARS-CoV, SARS-CoV-2 utilises the Spike glycoprotein on the envelope to recognise...
Preprint
Full-text available
SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 13 May 2020, has infected over 4 million people. Despite the urgent need to find effective therapeutics, research on SARS-CoV-2 has been affected by a lack of suitable animal models. To facilitate the developm...
Preprint
Full-text available
The Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2). The virus has rapidly spread in humans, causing the ongoing Coronavirus pandemic. Recent studies have shown that, similarly to SARS-CoV, SARS-CoV-2 utilises the Spike glycoprotein on the envelope to recognise...
Conference Paper
Lung cancer is the commonest cause of cancer death worldwide with a five-year survival rate of less than five percent for metastatic tumors. Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancer cases of which adenocarcinoma prevails. Patients almost invariably develop metastatic drug-resistant disease and this is responsible for our f...
Conference Paper
Lung cancer is the commonest cause of cancer death worldwide with a five-year survival rate of less than five percent for metastatic tumors. Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancer cases of which adenocarcinoma prevails. Patients almost invariably develop metastatic drug-resistant disease and this is responsible for our f...
Preprint
Most bacteria in nature exist in aggregated communities known as biofilms. Bacteria within biofilms are inherently highly resistant to antibiotics. Current understanding of the evolution and mechanisms of antibiotic resistance is largely derived from work from cells in liquid culture and it is unclear whether biofilms adapt and evolve in response t...
Article
Full-text available
Hybrid methods, which combine and integrate several biochemical and biophysical techniques, have rapidly caught up in the last twenty years to provide a way to obtain a fuller description of proteins and molecular complexes with sizes and complexity otherwise not easily affordable. Here, we review the use of a robust hybrid methodology based on a m...
Article
Full-text available
Methylation of cytosine is an epigenetic mark involved in the regulation of transcription, usually associated with transcriptional repression. In mammals, methylated cytosines are found predominantly in CpGs but in plants non-CpG methylation (in the CpHpG or CpHpH contexts, where H is A, C or T) is also present and is associated with the transcript...
Chapter
The current main challenge of Structural Biology is to undertake the structure determination of increasingly complex systems in the attempt to better understand their biological function. As systems become more challenging, however, there is an increasing demand for the parallel use of more than one independent technique to allow pushing the fronti...
Article
Full-text available
Stress caused by accumulation of misfolded proteins within the endoplasmic reticulum (ER) elicits a cellular unfolded protein response (UPR) aimed at maintaining protein-folding capacity. PERK, a key upstream component, recognizes ER stress via its luminal sensor/transducer domain, but the molecular events that lead to UPR activation remain unclear...
Article
Full-text available
We have exploited the capability of in-cell NMR to selectively observe flexible regions within folded proteins to carry out a comparative study of two members of the highly conserved frataxin family which are found both in prokaryotes and in eukaryotes. They all contain a globular domain which shares more than 50% identity, which in eukaryotes is p...
Article
Full-text available
Ire1 is activated in response to accumulation of misfolded proteins within the endoplasmic reticulum as part of the unfolded protein response (UPR). It is a unique enzyme, possessing both kinase and RNase activity that is required for specific splicing of Xbp1 mRNA leading to UPR activation. How phosphorylation impacts on the Ire1 splicing activity...
Article
Full-text available
The unfolded protein response (UPR) is a cell-signaling system that detects the accumulation of unfolded protein within the endoplasmic reticulum (ER) and initiates a number of cellular responses to restore ER homeostasis. The presence of unfolded protein is detected by the ER-luminal sensor domains of the three UPR-transducer proteins IRE1, PERK,...
Article
Protein surface accessibility is a critical parameter which drives all intermolecular interaction processes. In this respect a big deal of information has been derived by analyzing paramagnetic perturbation profiles obtained from NMR protein spectra, particularly in the case that the effects due to different soluble paramagnets can be compared. Her...
Article
Full-text available
The surface accessibility of {\alpha}-bungarotoxin has been investigated by using Gd2L7, a newly designed paramagnetic NMR probe. Signal attenuations induced by Gd2L7 on {\alpha}-bungarotoxin C{\alpha}H peaks of 1H-13C HSQC spectra have been analyzed and compared with the ones previously obtained in the presence of GdDTPA-BMA. In spite of the diffe...
Data
Supplementary Figure S1, Supplementary Tables S1–S2, Supplementary Discussion and Supplementary References
Article
IscS and IscU, the two central protein components of the iron sulfur cluster assembly machinery, form a complex that is still relatively poorly characterized. In an attempt to standardize the purification of these proteins for structural studies we have developed a protocol to produce them individually in high concentration and purity. We show that...
Article
Full-text available
Reduced levels of frataxin, an essential protein of as yet unknown function, are responsible for causing the neurodegenerative pathology Friedreich's ataxia. Independent reports have linked frataxin to iron-sulphur cluster assembly through interactions with the two central components of this machinery: desulphurase Nfs1/IscS and the scaffold protei...
Article
Full-text available
Frataxin is a highly conserved nuclear-encoded mitochondrial protein whose deficiency is the primary cause of Friedreich's ataxia, an autosomal recessive neurodegenerative disease. The frataxin structure comprises a well-characterized globular domain that is present in all species and is preceded in eukaryotes by a non-conserved N-terminal tail tha...
Article
Full-text available
Frataxin is an essential mitochondrial protein whose reduced expression causes Friedreich's ataxia (FRDA), a lethal neurodegenerative disease. It is believed that frataxin is an iron chaperone that participates in iron metabolism. We have tested this hypothesis using the bacterial frataxin ortholog, CyaY, and different biochemical and biophysical t...
Article
Understanding how proteins are approached by surrounding molecules is fundamental to increase our knowledge of life at atomic resolution. Here, the surface accessibility of a multifunctional small protein, the archaeal protein Sso7d from Sulfolobus solfataricus, has been investigated by using TEMPOL and Gd(III)(DTPA-BMA) as paramagnetic probes. The...
Article
Protein surface accessibility represents a dimension of structural biology which has not been discussed in details so far, in spite of its fundamental role in controlling the molecular recognition process. In the present report the surface accessibility of alpha-bungarotoxin, a small and well characterized protein, has been investigated by analyzin...
Article
Paramagnetic probes, whose approach to proteins can be monitored by nuclear magnetic resonance (NMR) studies, have been found to be of primary relevance for investigating protein surfaces' accessibility. Here, a Gd(III) neutral complex which contains two metal ions, [Gd2(L7)(H2O)2], is suggested as a paramagnetic probe particularly suited for syste...
Article
Paramagnetic probes, whose approach to proteins can be monitored by nuclear magnetic resonance (NMR) studies, have been found of primary relevance for investigating protein surfaces accessibility. Here, paramagnetic probes are also suggested for a systematic investigation on protein aggregation. Bovine pancreatic trypsin inhibitor (BPTI) was used a...
Article
Full-text available
SARS coronavirus, SCV, has been recently responsible of a sudden and widespread infection which caused almost 800 victims. The limited amount of SCV protein structural information is partially responsible of the lack of specific drugs against the virus. Coronavirus helicases are very conserved and peculiar proteins which have been proposed as suita...
Article
Full-text available
A structural genomics approach is proposed for the development of new diagnostic kits. It combines molecular modelling, peptide synthesis and immunological tests. The preliminary step is the development of a reliable three-dimensional structure of an immunodominant protein of the target pathogenic organism using the various bioinformatic strategies...
Article
Full-text available
The S1 and S2 subunits of the spike glycoprotein of the coronavirus which is responsible for the severe acute respiratory syndrome (SARS) have been modelled, even though the corresponding amino acid sequences were not suitable for tertiary structure predictions with conventional homology and/or threading procedures. An indirect search for a protein...

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