Dr Valentina Di Pietro PhD

Valentina Di Pietro

Institute of Inflammation and Ageing
Birmingham-Illinois BRIDGE fellow

Contact details

Address
Institute of Inflammation and Ageing
Robert Aitken
Institute for Clinical Research
Mindelsohn Way
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Dr Di Pietro is a Molecular Neuroscientist with a MSc in Molecular Biology, a PhD in Clinical Biochemistry and a further degree in Medical Genetics. With almost 20 years of research experience with particular interest in the molecular mechanisms of TBI, she is an expert of in vitro and in vivo animal models of TBI.

She currently leads the research efforts on microRNA signatures in biofluids to diagnose mild and severe TBI in patients. As the recipient of the prestigious BRIDGE Fellowship in Brain Trauma, she is a Research Fellow at the Institute of Inflammation and Ageing of the University of Birmingham (UK), collaborating with the Beckman Institute at the University of Illinois, Urbana-Champaign (USA) on TBI neuroimaging research.

Qualifications

  • Birmingham-Illinois BRIDGE fellow in Brain Trauma, April 2017.
  • Clinical Molecular Geneticists (4 years training scheme), University of Catania, Italy, 2010.
  • Thesis: Clinical, biochemical and molecular diagnosis of a compound homozygote for the 254 bp deletion-8 bp insertion of the APRT gene suffering from severe renal failure.
  • PhD in Biochemical Studies of Proteomics, Sacro Cuore, Catholic University of Rome, Italy, 2007.
  • Thesis: N-Acetyleaspartate (Naa) Metabolism in Acute and Chronic Neurodegenerative Diseases.
  • MSc. in Molecular Biology (full marks and honours), University of Catania, Italy, 2003.
  • Thesis: Biological effects of Proton and Photon Beams.

Biography

Dr Valentina Di Pietro is a Molecular Neuroscientist with experience in Genetics, Biochemistry and Molecular Biology. During her PhD at the Catholic University of Rome, she specialised in the identification of biomarkers for the diagnosis of mild, repeated and severe traumatic brain injury (TBI) with a focus on the molecular mechanisms of trauma.

She has also been involved in the setup of a new analytical HPLC method for the determination of biochemical markers of Inborn Errors of Metabolism (IEM) and she was in charge of the genetic analysis of related mutations.

In 2008, she joined the Division of Clinical Neurosciences at the University of Southampton where she was involved in the development of an in vitro model of acute neurodegenerative diseases. This model is now recognised as some of the most applicable alternatives to the use of in vivo experiments.

In 2012, dr Di Pietro joined the Institute of Inflammation and Ageing at the University of Birmingham where she is studying MicroRNAs as biomarkers in serum, urine and saliva of TBI patients and the potential role of MicroRNA-based therapy for trauma.

In 2017, Valentina Di Pietro was awarded the prestigious BRIDGE fellowship to undertake TBI research in collaboration with the University of Urbana-Champaign Illinois, USA. The fellowship allows dr Di Pietro to combine neuroimaging techniques available in the US with the results of microRNA study.

Dr Di Pietro also became board member and Chief Scientific Officer of a new company called Marker Diagnostics, interested in the development and commercialisation of the first salivary test to identify concussion using microRNAs.

Teaching

Postgraduate supervision

  • Two PhD students
  • 1 Lab technician

Research

MicroRNAs signature in Traumatic Brain Injury (TBI): diagnosis, prognosis and functional studies

Valentina Di Pietro, Antonio Belli

We have discovered that several microRNAs are expressed in blood, saliva and urine of TBI patients within minutes of injury. These are differentially expressed in different TBI severities and outcomes, reflecting differential pathophysiological responses to injury. MicroRNAs are silencing and post-transcriptional regulators of gene expression, and capture the multidimentionality of host-response at tissue and systemic level. They modulate downstream processes in brain and systemic targets, and dynamically continue to do so as the pathology evolves. The discovery of a new regulatory signalling into TBI pathology represents a step-change for molecular TBI research. 

SCRUM study: Study of Concussion in Rugby Union testing microRNAs

Valentina Di Pietro, Antonio Belli, Patrick Ohalloran, Kamal Yakoub, Conor Bentley, Callum Watson, Ugo Scarpa, David Davis

This study is carried out in association with the Rugby Football Union (RFU), Premiership Rugby and the Rugby Players' Association. During matches in 2017-18, players with confirmed or suspected concussion will provide saliva and urine samples immediately following the injury and will give follow-up samples as they go through the return-to-play protocol. Samples will be used to test microRNAs as biomarkers of concussion. The study will run alongside the existing Head Injury Assessments (HIA) and if the results support those found in laboratory tests, a new pitch-side test on a device will be developed.

Biomarkers of TBI and neuroimaging

Valentina Di Pietro, Antonio Belli, Aron K Barbey (University of Illinois)

Biomarkers (microRNAs/proteins/metabolites) identified in different bio-fluids of our cohort of concussed athletes will be correlated with the most advanced neuroimaging techniques (MRI, fMRI, DTI, MRE, MRS) and a battery of neurocognitive tests available at the Biomedical Imaging Center at the Beckman Institute of Illinois. The integration of biomarkers, neuroimaging and neuropsychology in a single sample would allow for comparison across multiple measurements resulting in refinement of their individual diagnostic, prognostic and clinical utility as well as in evaluating their effectiveness to detect neural and cognitive recovery.

A characterisation of exosomes within different bio-fluids following concussion and potential therapeutic applications

Callum Watson, Paul Harrison, Valentina Di Pietro

Exosomes (40nm-100nm in diameter) are forms of extracellular vesicles (EVs) that affect disease processes through their involvement in inter cell communication. Their composition is varied, containing numerous signalling molecules including DNA, RNA and proteins appropriate for signalling at the target location which if changed could detail important components in concussion phenotype, demonstrating their potential as a clinical biomarker. Exosomes have potential as biomarkers if changes during a disease process are consistent and measureable with two potential methods of monitoring changes; through change in exosome number or change in composition of exosomes. We aim to demonstrate that: concussed patients will have an increase in exosome number which could be objectively measured in different bio-fluids and miRNA profiles will be distinct between concussed and healthy patients and based on the bio-fluid analysed.

MiRNA functional study

Callum Watson, Valentina Di Pietro

Multiple methodologies are now available to ascertain miRNA targeting. The luciferase test is the most used to experimentally validate the bioinformatically predicted mRNA targets. Understanding the biological role of the microRNA differentially expressed in pathological state (such as mild TBI) is quiet relevant to explore and understand the possibility of using miRNA as therapeutic agents or identifying new therapeutic pathways. In this study we want to investigate the biological role of microRNAs differentially expressed in TBI with the aim to use it in the near future as potential therapeutic drug or to identify new area for therapeutic interventions. Understand the biology hidden by this microRNA is fundamental to restore its normal biological function.

Neuro-inflammatory proteins in TBI

Valentina Di Pietro, Antonio Belli

Within minutes of a traumatic impact, a robust inflammatory response is elicited in the injured brain. Neuroinflammation is responsible for both beneficial and detrimental effects, contributing to secondary brain damage but also facilitating neurorepair. For all these reasons, these inflammatory molecules could satisfy the main characteristics required for a biomarker in the diagnosis and prognosis of TBI. In particular, the early identification of these biomarkers could permit clinicians to recognise and treat those patients at risk of secondary injury while they are still capable of responding to therapy before irreversible damages occur.

Changes of metabolism in severe and mild TBI in an in vivo animal model

Valentina Di Pietro, Antonio Belli, Giuseppe Lazzarino (University of Catania), Barbara Tavazzi (Catholic University of Rome)

Using different approaches (HPLC to analyse biochemical alterations of energy metabolism and oxidative/nitrosative stresses, microarray to analyse gene expression profile) the metabolic, enzymatic and gene changes following graded diffuse traumatic brain injury (TBI) are studied in a weight drop model of TBI in rats.

Micro-optofluidic engineered device technology (MEDtech) for timely assessment of TBI

Pola Goldberg Oppenheimer, Valentina Di Pietro, Antonio Belli

In this project a highly-innovative, reliable, diagnostic technology for rapid detection of biomarkers at a picomolar range capable of discriminating between different analytes from complex bio-fluids has been developed. The portable, minimally-invasive MEDTech is based on cost-effective, controllable electrohydrodynamic (EHD) sub-microstructures engineered for multiplexed-surface enhanced Raman scattering (SERS) detection. It combines sensitive, reproducible and molecule-specific EHD-SERS lab-on-a-chip with miniaturised optofluidic platforms for on-the-spot biomarkers detection, either individually or as a panel, to enable real-time diagnostics and care-delivery.

MiRNA-protein co-expression analysis in neurodegenerative disease as long-term consequences of multiple concussions

Callum Watson, Valentina Di Pietro

Over the last decade, concerns have focused on the possibility that, for some athletes, repetitive concussions may raise long-term neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson or Chronic Traumatic Encephalopathy (CTE). In the current study, we are carrying on an integrated miRNA-protein co-expression analysis to uncover the potential roles of miRNA in neurodegenerative diseases with the aim to identify new therapeutic targets.

Other activities

  • Consultancy activities for Marker Diagnostics UK Ltd.
  • IIA Health and Safety committee member.
  • Tweeter administrator for the Neurotrauma and Ophthalmology group (UoB).
  • PERCAT committee member.
  • Member of the British Neuroscience Society (BNA), Federation of European Neuroscience Societies (FENS) and the International Brain Research Organisation (IBRO).

Publications

Recent publications

Article

Begum, G, Reddy, R, Yakoub, KM, Belli, A, Davies, DJ & Di Pietro, V 2020, 'Differential expression of circulating inflammatory proteins following sport-related traumatic brain injury', International Journal of Molecular Sciences, vol. 21, no. 4, 1216. https://doi.org/10.3390/ijms21041216

Lazzarino, G, Amorini, AM, Barnes, NM, Bruce, L, Mordente, A, Lazzarino, G, Pietro, VD, Tavazzi, B, Belli, A, Logan, A & Nagy, Z 2020, 'Low molecular weight dextran sulfate (ILBĀ®) administration restores brain energy metabolism following severe traumatic brain injury in the rat', Antioxidants, vol. 9, no. 9, 850. https://doi.org/10.3390/antiox9090850

Rickard, J, Di Pietro, V, Smith, D, Davies, D, Belli, T & Goldberg Oppenheimer, P 2020, 'Rapid optofluidic detection of biomarkers for traumatic brain injury via surface-enhanced Raman spectroscopy', Nature Biomedical Engineering. https://doi.org/10.1038/s41551-019-0510-4

Rickard, JJS, Di-Pietro, V, Smith, DJ, Davies, DJ, Belli, A & Oppenheimer, PG 2020, 'Rapid optofluidic detection of biomarkers for traumatic brain injury via surface-enhanced Raman spectroscopy', Nature Biomedical Engineering, vol. 4, no. 6, pp. 610-623. https://doi.org/10.1038/s41551-019-0510-4

Yakoub, KM, Lazzarino, G, Amorini, AM, Caruso, G, Scazzone, C, Ciaccio, M, Tavazzi, B, Lazzarino, G, Belli, A & Di Pietro, V 2019, 'Fructose-1,6-Bisphosphate Protects Hippocampal Rat Slices from NMDA Excitotoxicity', International Journal of Molecular Sciences, vol. 20, no. 9, 2239. https://doi.org/10.3390/ijms20092239

Yakoub, KM, Davies, DJ, Su, Z, Bentley, C, Forcione, M, Toman, E, Hammond, D, Watson, CN, Bishop, J, Cooper, L, Barbey, AK, Sawlani, V, Di Pietro, V, Grey, MJ & Belli, A 2019, 'Investigation into repetitive concussion in sport (RECOS): study protocol of a prospective, exploratory, observational cohort study', BMJ open, vol. 9, no. 7, pp. e029883. https://doi.org/10.1136/bmjopen-2019-029883

Lazzarino, G, Amorini, AM, Signoretti, S, Musumeci, G, Lazzarino, G, Caruso, G, Pastore, FS, Di Pietro, V, Tavazzi, B & Belli, A 2019, 'Pyruvate Dehydrogenase and Tricarboxylic Acid Cycle Enzymes Are Sensitive Targets of Traumatic Brain Injury Induced Metabolic Derangement', International Journal of Molecular Sciences, vol. 20, no. 22. https://doi.org/10.3390/ijms20225774

Hill, LJ, Di Pietro, V, Hazeldine, J, Davies, D, Toman, E, Logan, A & Belli, A 2018, 'Author Correction: Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury', Scientific Reports, vol. 8, 4572. https://doi.org/10.1038/s41598-018-22951-0

Di Pietro, V, Porto, E, Ragusa, M, Barbagallo, C, Davies, D, Forcione, M, Logan, A, Di Pietro, C, Purrello, M, Grey, M, Hammond, D, Sawlani, V, Barbey, AK, Belli, A & Yakoub, K 2018, 'Salivary microRNAs: diagnostic markers of mild traumatic brain injury in contact-sport', Frontiers in Molecular Neuroscience, vol. 11, 290. https://doi.org/10.3389/fnmol.2018.00290

Yakoub, KM, O'Halloran, P, Davies, DJ, Bentley, C, Watson, CN, Forcione, M, Scarpa, U, Bishop, JRB, Toman, E, Hammond, D, Cross, MJ, Stokes, KA, Kemp, SPT, Menon, DK, Di Pietro, V & Belli, A 2018, 'Study of Concussion in Rugby Union through MicroRNAs (SCRUM): a study protocol of a prospective, observational cohort study', BMJ open, vol. 8, no. 11, e024245. https://doi.org/10.1136/bmjopen-2018-024245

Abstract

Di Pietro, V, O'Halloran, P, Scarpa, U, Watson, C, Yakoub, K, Bentley, C, Davies, D, Cross, M, Stokes, K, Kemp, S & Belli, A 2018, 'Salivary micrornas for the diagnosis and management of sport concussion in professional Rugby Union', Journal of Neurotrauma, vol. 35, no. 16, PS1.04.186. https://doi.org/10.1089/neu.2018.29013.abstracts

Davies, D, Yakoub, K & Di Pietro, V 2018, 'Serum miR-502: a sensitive biomarker for the diagnosis of concussion in patients with normal brain imaging', Frontiers in Traumatic Brain Injury 2018, London, United Kingdom, 5/07/18 - 6/07/18.

Review article

Di Pietro, V, Yakoub, KM, Caruso, G, Lazzarino, G, Signoretti, S, Barbey, AK, Tavazzi, B, Lazzarino, G, Belli, A & Amorini, AM 2020, 'Antioxidant Therapies in Traumatic Brain Injury', Antioxidants, vol. 9, no. 3. https://doi.org/10.3390/antiox9030260

Watson, CN, Belli, A & Di Pietro, V 2019, 'Small Non-coding RNAs: New Class of Biomarkers and Potential Therapeutic Targets in Neurodegenerative Disease', Frontiers in Genetics, vol. 10, 364. https://doi.org/10.3389/fgene.2019.00364

Di Pietro, V, Yakoub, K, Scarpa, U, Di Pietro, C & Belli, A 2018, 'MicroRNA Signature of Traumatic Brain Injury: From the Biomarker Discovery to the Point-of-Care', Frontiers in neurology, vol. 9, no. 429, 429. https://doi.org/10.3389/fneur.2018.00429

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