Dr Valentina Di Pietro PhD

Dr Valentina Di Pietro

Institute of Inflammation and Ageing
Birmingham-Illinois BRIDGE fellow (Brain Trauma)

Contact details

Address
Institute of Inflammation and Ageing
Robert Aitken institute for clinical research
off Mindelsohn way
University of Birmingham
Edgbastion
B152TT

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.

Valentina Di Pietro was recently 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 the five years microRNA study.

Dr Di Pietro is also founder and board member of a new company “Biovici diagnostic ltd” interested in the development of a point-of-care diagnostics device for TBI patient stratification.

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.

  • Ph.D. in Biochemical Studies of Proteomics, Sacro Cuore, Catholic University of Rome, Italy, 2007.
  • Thesis: N-Acetyleaspartate (Naa) Metabolism in Acute and Chronic Neurodegenerative Diseases.

  • M.Sc. in Molecular Biology (full marks and honours), University of Catania, Italy, 2003.
  • Thesis: Biological effects of Proton and Photon Beams.

Teaching

  • Research Taster, 1st year students, University of Birmingham (2014-present)
  • Tutor of Experimental Design Module for the 2nd year students, University of Birmingham (2014)
  • Tutor of Molecular Biology Module for the 2nd year students of Biomedical School at University of Birmingham (2013-2016)
  • Tutor of International PhD students and ERASMUS students at the University of Birmingham
  • Tutor of 15 BioMed/MSc students at the University of Birmingham.

Postgraduate supervision

  • 1 PhD student
  • 2 Lab technicians
  • Co-supervisor of 1 International post-Doc at the Catholic University of Rome

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.

Development of TBI point-of-care diagnostic devices

Valentina Di Pietro, Ugo Scarpa, Antonio Belli, Biovici diagnostics Ltd

Over 1.4 million people attend UK Emergency Department every year with a TBI. Many more suffer concussion during contact sports but are not treated in hospital. Timely diagnosis of TBI is key. We have identified highly sensitive, ultra-early biomarkers of TBI consisting of microRNAs. However, a sensitive biomarker would be no used for roadside or pitch-side diagnosis if samples still needed analysing in a hospital lab. We have therefore partnered with Biovici diagnostic Ltd, a company who is developing a rapid portable and low-cost detection method.

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.

INSIGHT project

Valentina Di Pietro, Joachim T Operskalski (University of Illinois), Aron K Barbey (University of Illinois)

Saliva samples of TBI patients were collected at the Beckaman Institute together with neuroimaging (MRE, MRI) and neurocognitive assessments. Samples will be used for the analysis of DNA polymorphism and correlated with            cognitive and behavioural indicators in relation to neuroimaging. The final aim is to characterize the processes of recovery.

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

Valentina Di Pietro, Callum Watson, Antonio Belli

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

Valentina Di Pietro, Adam Thompson, Antonio Belli

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.

Neurobioreactors: a new in vitro stretch injury device

Valentina Di Pietro, Adam Thomposn, Lisa J Hill, Antonio Belli, Alastair Campbell Ritchie (University of Nottingham).

This project developed a reliable and reproducible platform for testing drugs and other neuroprotective strategies using an in vitro model of organotypic hippocampal slice cultures. The cultures are stretched on a silicone membrane to mimic in vivo tissue deformation experienced during TBI. The novelty of this study is to understand the molecular changes occurring in TBI in a “clean” environment without the systemic confounders of the in vivo model.  A prototype of the model has already been built thanks to the ongoing collaboration with Dr Alastair Campbell Ritchie (UoN). The prototype uses pneumatic pressure as the actuation method, giving greater flexibility in stimulation regimens than current methods using direct physical displacement.

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.

Other activities

  • Consultancy activities for TIKOMED:
  • A new drug will be tested in an animal model for the treatment of acute TBI.

  • Board member of a new spin-out company BIOVICI diagnostics
  • Consultancy activities for BIOVICI diagnostics ltd: The company is developing a new point of care testing device for the diagnosis of TBI.
  • 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

Hill LJ, Di Pietro V, Hazeldine J, Davies D, Tomman E, Logan A, Belli A (2017) Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury. Sci Rep 10;7(1):5002.

Di Pietro V, Ragusa M, Davies D, Su Z, Hazeldine J, Lazzarino G, Hill LJ, Crombie N, Foster M, Purrello M, Logan A, Belli A (2017) MicroRNAs as Novel Biomarkers for the Diagnosis and Prognosis of Mild and Severe Traumatic Brain Injury. J Neurotrauma 1;34(11):1948-1956.

Amorini AM, Lazzarino G, Di Pietro V, Signoretti S, Lazzarino G, Belli A and Tavazzi B (2016) Metabolic, enzymatic and gene involvement in cerebral glucose dysmetabolism after traumatic brain injury. Biochim Biophys Acta pii:S0925-4439(16)30026-6.

Di Pietro V, Amorini AM, Lazzarino G, Yakoub KM, D'Urso S, Lazzarino G and Belli A (2015) S100B and Glial Fibrillary Acidic Protein as Indexes to Monitor Damage Severity in an In Vitro Model of Traumatic Brain Injury. Neurochem Res 40(5):991-9.

Bracko O, Di Pietro V, Lazzarino G, Amorini AM, Tavazzi B, Artmann J, Wong EC, Buxton RB, Weller M, Luft AR and Wegener S (2014) 3-Nitropropionic acid-induced ischemia tolerance in the rat brain is mediated by reduced metabolic activity and cerebral blood flow. J Cereb Blood Flow Metab 34(9):1522-30.

Amorini AM, Nociti V, Petzold A, Gasperini C, Quartuccio E, Lazzarino G, Di Pietro V, Belli A, Signoretti S, Vagnozzi R, Lazzarino G and Tavazzi B (2014) Serum lactate as a novel potential biomarker in multiple sclerosis. Biochim Biophys Acta 1842(7):1137-43.

Bulstrode H, Nicoll JA, Hudson G, Chinnery PF, Di Pietro V and Belli A (2014) Mitochondrial DNA and traumatic brain injury. Ann Neurol 75(2):186-95.

Di Pietro V, Amorini AM, Tavazzi B, Vagnozzi R, Logan A, Lazzarino G, Signoretti S, Lazzarino G and Belli A (2014) The molecular mechanisms affecting N-acetylaspartate homeostasis following experimental graded traumatic brain injury. Mol Med 20:147-57.

Di Pietro V, Lazzarino G, Amorini AM, Tavazzi B, D'Urso S, Longo S, Vagnozzi R, Signoretti S, Clementi E, Giardina B, Lazzarino G and Belli A (2014) Neuroglobin expression and oxidant/antioxidant balance after graded traumatic brain injury in the rat. Free Radic Biol Med 69:258-64.

View all publications in research portal