Dr Valentina Di Pietro PhD

Valentina Di Pietro

Institute of Inflammation and Ageing
Associate Professor of Neurotrauma

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 Traumatic Brain Injury (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.

Qualifications

  • PGcert in Higher Education, University of Birmingham, UK, 2020
  • Clinical Molecular Geneticists (4 years training scheme) (full marks and honors), State University of Catania, Italy, 2003-2004 /2007-2010 
  • Ph.D. program (Biochemical Studies of Proteomics) (full marks and honors), Sacro Cuore, Catholic University of Rome, Italy, 2004-2007 
  • Master Degree in Biological Sciences (full marks and honors), State University of Catania, Italy, 2003

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.

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

Dr Di Pietro is also founder and consultant of a new company “Marker Health AG” interested in the development of diagnostics test for TBI patient stratification.

Teaching

  • MSc Trauma Science
  • BSc Neuroscience, Endocrinology and Reproduction
  • BSc Neurotrauma: Degeneration & Regeneration
  • MSc Translational Medicine
  • Research Taster
  • BSc Foundations of Neuroscience
  • BSc Foundations of Pharmacology

Postgraduate supervision

  • Two PhD students
  • 1 Lab technician

Research

MicroRNAs as diagnostic makers of Traumatic Brain Injury (TBI

Dr Valentina Di Pietro, Prof Antonio Belli

TBI is incorrectly diagnosed in over half the cases of major trauma, which can cause delays in implementing the correct management and wastage of healthcare resources. In 2013, using an in vitro TBI model, I identified that mild TBI triggers a controlled gene programme as an adaptive response for neuroprotection. I subsequently hypothesised that the body could systemically orchestrate the optimal response to injury by exchanging relevant microRNA signals.

In 2014, In the “Golden Hour” study, a pioneering project in collaboration with the West Midlands Ambulance and Air Ambulance trusts, where blood samples are collected immediately at the roadside and within the first hour from trauma victims, I identified  microRNA changes in plasma in a cohort of 120 patients (https://pubmed.ncbi.nlm.nih.gov/28279125/ ) . As blood is not ideal for the diagnosis of TBI in austere environments, in children or pitch-side, particularly at the milder end of the spectrum (i.e. concussion), I investigated microRNAs in saliva and urine as part of our Repetitive Concussion in Sport study (RECOS).  I identified a panel of non-invasive microRNA biomarkers in a cohort of 52 professional athletes (https://pubmed.ncbi.nlm.nih.gov/30177873/).

To validate the panel, in 2017, and in partnership with England’s Rugby Football Union, the largest ever study on sport concussion was launched. The study has recruited over 1200 players and was published in JBSM (2021) (https://pubmed.ncbi.nlm.nih.gov/33757972/).

Long-term consequences of repetitive concussions: The molecular signature of the point of no return

Dr Valentina Di Pietro, Prof Zubair Ahmed, Prof Claudio Mauro, Prof Giuseppe Lazzarino, Prof Barbara Tavazzi

Concussion, also known as mild Traumatic Brain Injury (mTBI), is a transient disturbance of normal neurological function that results from a rapid rotational acceleration of the brain and showing no gross structural injury using conventional neuroimaging. The cognitive effects of concussion (such as memory problems, communication, personality changes, as well as depression) appear after injury and in most cases improve spontaneously over time. However, in some cases, these changes can persist, especially if multiple concussions are sustained within a vulnerable time period. Several pre-clinical studies, including ours, using an adult rodent model of repeated weight drop injuries, have shown a window of metabolic derangement post-injury, during which there is an increased vulnerability to further injury. However, it is not yet clear if  a specific number of repeated concussions triggers to permanent biochemical/molecular resulting into dementia-like pathologies. Therefore, the need for studies to address the signature of the point of no return, that will irreversibly lead to a neurodegenerative conditions, is mandatory and particularly important in contact and collision sports where a higher incidence of concussions is reported. We hypothesise that response of each individual to injuries may operate according to a "molecular threshold", beyond which is leading to relentless tissue destruction and functional loss. Significant long-term cognitive deficits were associated with three or more lifetime mTBIs, however, is still evident the need of more objective and personalized criteria to help clinicians to understand whether or not a retirement for an athlete should be considered.

Crosstalk between TGFb signaling and microRNA machinery in Alzheimer’s disease

Dr Valentina Di Pietro, Dr Lisa Hill, Prof  Zsuzsa Nagy

Alzheimer’ Disease (AD) is a progressive neurodegenerative condition, resulting in memory loss, decreased processing speed, impaired executive function and associated low mood and/or irritability. The cellular mechanisms underlying AD are varied and complex, they include neuronal loss, synaptic pruning, mitochondrial dysfunction and glial cell alterations. There are two clear pathological hallmarks: amyloid β plaques and Neurofibrillary Tangles (NFTs), however over the last decade, the presence of a sustained immune response in the brain has emerged as a third core pathology in AD.

An interesting role is played by TGFb  signaling and increasing evidence indicates how disruption of this pathway contributes to the AD pathogenesis. TGFb is involved in the regulation of cell growth, cell differentiation and immunosuppression. It plays a neuroprotective against ab production, deposition and damage, and inhibits the pathway for the tau-phosphorylation enzyme GSK-3b.

Recently, it has been shown that the TGFb pathway embraces  miRNA pathway as an important component of its downstream signaling cascade.

Neuroimaging and Traumatic Brain Injury

Dr Valentina Di Pietro, Prof Antonio Belli,Prof  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.

Other activities

  1. Co-founder, shareholder and specialist consultant for Marker Health (https://markerhealth.com/).
  2. Academic Integrity Officer (IIA)
  3. REF reading group (IIA)
  4. IIA website working group
  5. First Aider for Neurotrauma group
  6. InTBIR working group (InTBIR | https://intbir.incf.org/), 
  7. Birmingham Centre for Neurogenetics committee

UK and international memberships

  • European Neurotrauma Organisation (ENO)
  • Fellow of the Higher Education Academy (FHEA)
  • British Neuroscience Society (BNA)
  • Federation of European Neuroscience Societies (FENS)
  • International Brain Research Organisation (IBRO).

Publications

Recent publications

Article

Mangione, R, Giallongo, C, Duminuco, A, La Spina, E, Longhitano, L, Giallongo, S, Tibullo, D, Lazzarino, G, Saab, MW, Sbriglione, A, Palumbo, GA, Graziani, A, Alanazi, AM, Di Pietro, V, Tavazzi, B, Amorini, AM & Lazzarino, G 2024, 'Targeted Metabolomics Highlights Dramatic Antioxidant Depletion, Increased Oxidative/Nitrosative Stress and Altered Purine and Pyrimidine Concentrations in Serum of Primary Myelofibrosis Patients', Antioxidants, vol. 13, no. 4, 490. https://doi.org/10.3390/antiox13040490

Anderson, ED, Talukdar, T, Goodwin, G, Di pietro, V, Yakoub, KM, Zwilling, CE, Davies, D, Belli, A & Barbey, AK 2023, 'Assessing blood oxygen level-dependent signal variability as a biomarker of brain injury in sport-related concussion', Brain Communications, vol. 5, no. 4, fcad215. https://doi.org/10.1093/braincomms/fcad215

Mangione, R, Pallisco, R, Bilotta, G, Marroni, F, Di Pietro, V, Capoccia, E, Lazzarino, G, Tavazzi, B, Lazzarino, G, Bilotta, P, Amorini, AM & Pavlović, SZ (ed.) 2023, 'Bilirubin Concentration in Follicular Fluid Is Increased in Infertile Females, Correlates with Decreased Antioxidant Levels and Increased Nitric Oxide Metabolites, and Negatively Affects Outcome Measures of In Vitro Fertilization', International Journal of Molecular Sciences, vol. 24, no. 13, 10707. https://doi.org/10.3390/ijms241310707

Awuson-David , B, Williams, AC, Wright, B, Hill, LJ & Di Pietro, V 2023, 'Common microRNA regulated pathways in Alzheimer’s and Parkinson’s disease', Frontiers in Neuroscience, vol. 17, 1228927. https://doi.org/10.3389/fnins.2023.1228927

Lazzarino, G, Mangione, R, Saab, MW, Tavazzi, B, Pittalà, A, Signoretti, S, Di Pietro, V, Lazzarino, G & Amorini, AM 2023, 'Traumatic Brain Injury Alters Cerebral Concentrations and Redox States of Coenzymes Q9 and Q10 in the Rat', Antioxidants, vol. 12, no. 5, 985. https://doi.org/10.3390/antiox12050985

Logan, A, Nagy, Z, Barnes, N, Belli, T, Di Pietro, V, Tavazzi, B, Lazzarino, G, Lazzarino, G, Bruce, L & Persson, LI 2022, 'A phase II open label clinical study of the safety, tolerability and efficacy of ILB® for amyotrophic lateral sclerosis', PLOS One, vol. 17, no. 5, e0267183. <http://10.1371/journal.pone.0267183>

Watson, CN, Begum, G, Ashman, E, Thorn, D, Yakoub, KM, Hariri, MA, Nehme, A, Mondello, S, Kobeissy, F, Belli, A & Di Pietro, V 2022, 'Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer’s Disease Patients', Cells, vol. 11, no. 1, 163. https://doi.org/10.3390/cells11010163

Toman, E, Riley, M, Hodgson, S, Yakoub, KM, Cooper, L, Bishop, J, Naumann, DN, Welbury, R, Hammond, D, Di Pietro, V & Belli, A 2022, 'Concussion in Non-athletes: Assessment of Cognition and Symptomatology (CONTACTS) study protocol - an exploratory cohort study investigating the utility of sports concussion assessment tools and salivary microRNAs to diagnose concussion in NHS patients', BMJ open, vol. 12, no. 9, e062030. https://doi.org/10.1136/bmjopen-2022-062030

Lazzarino, G, Di Pietro, V, Rinaudo, M, Nagy, Z, Barnes, N, Bruce, L, Signoretti, S, Mangione, R, Saab, MW, Tavazzi, B, Belli, T, Lazzarino, G, Amorini, AM & Logan, A 2022, 'ILB®, a low molecular weight dextran sulphate, restores glutamate homeostasis, amino acid metabolism and neurocognitive functions in a rat model of severe traumatic brain injury', International Journal of Molecular Sciences, vol. 23, no. 15, 8460. https://doi.org/10.3390/ijms23158460

Davies, DJ, Hadis, M, Di Pietro, V, Lazzarino, G, Forcione, M, Harris, G, Stevens, A, Soon, WC, Goldberg Oppenheimer, P, Milward, M, Belli, T & Palin, W 2022, 'Photobiomodulation reduces hippocampal apoptotic cell death and produces a Raman spectroscopic “signature”', PLOS One, vol. 17, no. 3, e0264533. https://doi.org/10.1371/journal.pone.0264533

Logan, A, Belli, T, Di Pietro, V, Tavazzi, B, Lazzarino, G, Mangione, R, Lazzarino, G, Morano, I, Qureshi, O, Bruce, L, Barnes, N & Nagy, Z 2022, 'The mechanism of action of a novel neuroprotective low molecular weight dextran sulphate: new platform therapy for neurodegenerative diseases like Amyotrophic Lateral Sclerosis', Frontiers in Pharmacology, vol. 13, 13:983853. https://doi.org/10.3389/fphar.2022.983853

Review article

Wesolowski, E, Ahmed, Z & Di Pietro, V 2024, 'History of concussion and lowered heart rate variability at rest beyond symptom recovery: a systematic review and meta-analysis', Frontiers in neurology, vol. 14, 1285937. https://doi.org/10.3389/fneur.2023.1285937

Tasker, R, Rowlands, J, Ahmed, Z & Di Pietro, V 2021, 'Co-expression network analysis of micro-RNAs and proteins in the Alzheimer’s brain: a systematic review of studies in the last 10 years', Cells, vol. 10, no. 12, 3479. https://doi.org/10.3390/cells10123479

Osgood, C, Ahmed, Z & Di Pietro, V 2021, 'Co-expression network analysis of microRNAs and proteins in severe traumatic brain injury: a systematic review', Cells, vol. 10, no. 9, 2425. https://doi.org/10.3390/cells10092425

Khan, S, Ali, A, Kadir, B, Ahmed, Z & Di Pietro, V 2021, 'Effects of memantine in patients with traumatic brain injury: A systematic review', Traumas, vol. 1, no. 1, pp. 1-14. https://doi.org/10.3390/traumas1010001

View all publications in research portal

Expertise

Concussion; traumatic brain injury; biomarker