Dr Ola Rominiyi

BSc (Hons) MB ChB (Hons) MRCS PhD

Neuroscience, School of Medicine and Population Health

NIHR Clinical Lecturer in Neurosurgery

o.rominiyi@sheffield.ac.uk
+44 114 2711900

N125C, Royal Hallamshire Hospital

Full contact details

Dr Ola Rominiyi
Neuroscience, School of Medicine and Population Health
N125C
Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF

Profile

Ola Rominiyi studied medicine at the University of Manchester where he obtained a 1^st Class Honours degree in Physiology & Pharmacology and completed a degree in Clinical Medicine graduating with Honours in 2011.

After completing House Officer posts in Cambridge, King’s Lynn and Oxford, in 2014, Ola secured a highly competitive neurosurgical training number in Sheffield. During his neurosurgical training Ola developed a strong interest in neuro-oncology research as a means towards reducing the devastation brain tumours cause patients and families. Supported by a Royal College of Surgeons and Neurocare Clinical PhD Fellowship, and Yorkshire’s Brain Tumour Charity (formerly BTRS), he was awarded a PhD in Molecular Neuro-Oncology in 2020.

During Ola’s PhD, under the supervision Dr Spencer Collis, he identified novel combination treatment strategies based on multimodal targeting of the DNA damage response in glioblastoma. He also developed new clinically- and surgically-relevant patient-derived cancer stem cell models to establish the Sheffield ‘Living Biobank’ of Glioblastoma. In 2021, Ola was awarded Sheffield’s first NIHR Clinical Lectureship in Neurosurgery which enables him to combine ongoing clinical training with research as Translational Lead for the newly established Sheffield Translational Brain Tumour Research Group.

Current PhD Opportunities:

Deconvoluting the spatial multi-omic landscape of high-grade glioma to target post-surgical residual disease

Research interests: Understanding spatial intratumoural heterogeneity in high-grade brain tumours with a particular focus on responses to DNA damage and leveraging this knowledge to deliver new ways to monitor and treat disease in patients. I aim to combine a long-term ethos of excellence in clinical and surgical practice with internationally excellent academic research to ensure the best possible care and outcomes are extended to patients both now and in the future.

Publications

Journal articles

Poon MTC, Piper RJ, Thango N, Fountain DM, Marcus HJ, Lippa L, Servadei F, Esene IN, Freyschlag CF, Neville IS , Rosseau G et al (2023) Variation in postoperative outcomes of patients with intracranial tumors: insights from a prospective international cohort study during the COVID-19 pandemic. Neuro-Oncology, 25(7), 1299-1309.
Patel P, Alghamdi A, Shaw G, Legge C, Glover M, Freeman D, Hodgetts H, Wilson E, Howard F, Staniland S , Kennerley AJ et al (2023) Development of a personalised device for systemic magnetic drug targeting to brain tumours. Nanotheranostics, 7(1), 102-116.
McGarrity - Cottrell C, Myers K, Wang D, Dunning M, Bagga V, Al-Tamimi Y, Sinha S, Rominiyi O & Collis S (2022) STEM-02. GENERATION AND CHARACTERISATION OF A LIVING BIOBANK OF POST-SURGICAL RESIDUAL GLIOBLASTOMA TO IDENTIFY NOVEL THERAPEUTIC TARGETS. Neuro-Oncology, 24(Supplement_7), vii31-vii31.
Glasbey JC, Abbott TEF, Ademuyiwa A, Adisa A, AlAmeer E, Alshryda S, Arnaud AP, Bankhead-Kendall B, Abou Chaar MK, Chaudhry D , Costas-Chavarri A et al (2022) Elective surgery system strengthening: development, measurement, and validation of the surgical preparedness index across 1632 hospitals in 119 countries. The Lancet, 400(10363), 1607-1617.
Gillespie CS, Bligh ER, Poon MTC, Solomou G, Islim AI, Mustafa MA, Rominiyi O, Williams ST, Kalra N, Mathew RK , Booth TC et al (2022) Imaging timing after glioblastoma surgery (INTERVAL-GB): protocol for a UK and Ireland, multicentre retrospective cohort study. BMJ Open, 12(9), e063043-e063043.
Ooi SZY, Dada OE, Bukenya GW, Kenfack YJ, Le C, Ohonba E, Adeyemo E, Narain K, Awad AK, Barrie U , Sichimba D et al (2022) Evaluating the impact of neurosurgical rotation experience in Africa on the interest and perception of medical students towards a career in neurosurgery : a protocol for a continental, cross-sectional study. Journal of Surgical Protocols and Research Methodologies, 2022(2).
Dada OE, Ooi SZY, Bukenya GW, Kenfack YJ, Le C, Ohonba E, Adeyemo E, Narain K, Awad AK, Barrie U , Sichimba D et al (2022) Evaluating the impact of neurosurgical rotation experience in Africa on the interest and perception of medical students towards a career in neurosurgery : a continental, multi-centre, cross-sectional study. Frontiers in Surgery, 9.
Nepogodiev D, Simoes JFF, Li E, Picciochi M, Glasbey JC, Baiocchi G, Blanco‐Colino R, Chaudhry D, AlAmeer E, El‐Boghdadly K , Wuraola F et al (2022) SARS‐CoV‐2 infection and venous thromboembolism after surgery: an international prospective cohort study. Anaesthesia, 77(1), 28-39.
COVID Surg Collaborative (2021) Impact of Bacillus Calmette-Guérin (BCG) vaccination on postoperative mortality in patients with perioperative SARS-CoV-2 infection. BJS Open, 5(6).
Fountain DM, Piper RJ, Poon MTC, Solomou G, Brennan PM, Chowdhury YA, Colombo F, Elmoslemany T, Ewbank FG, Grundy PL , Hasan MT et al (2021) CovidNeuroOnc: A UK multicenter, prospective cohort study of the impact of the COVID-19 pandemic on the neuro-oncology service. Neuro-Oncology Advances, 3(1). View this article in WRRO
Glasbey J, Ademuyiwa A, Adisa A, AlAmeer E, Arnaud AP, Ayasra F, Azevedo J, Minaya-Bravo A, Costas-Chavarri A, Edwards J , Elhadi M et al (2021) Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study. The Lancet Oncology, 22(11), 1507-1517.
Nepogodiev D, Simoes JFF, Li E, Picciochi M, Glasbey JC, Baiocchi G, Blanco‐Colino R, Chaudhry D, AlAmeer E, El‐Boghdadly K , Wuraola F et al (2021) Effects of pre‐operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study. Anaesthesia, 76(11), 1454-1464.
Akowuah E, Benson RA, Caruana EJ, Chetty G, Edwards J, Forlani S, Gradinariu G, Murphy GJ, Oo AY, Patel AJ , Ridley B et al (2021) Early outcomes and complications following cardiac surgery in patients testing positive for coronavirus disease 2019: An international cohort study. The Journal of Thoracic and Cardiovascular Surgery, 162(2), e355-e372. View this article in WRRO
Rominiyi O, Vanderlinden A, Clenton SJ, Bridgewater C, Al-Tamimi Y & Collis SJ (2021) Correction: Tumour treating fields therapy for glioblastoma: current advances and future directions. British Journal of Cancer, 125(4), 623-623.
Rominiyi O & Collis SJ (2021) DDRugging glioblastoma: understanding and targeting the DNA damage response to improve future therapies.. Molecular Oncology. View this article in WRRO
Rominiyi O, Vanderlinden A, Myers K, Gomez-Roman N, Dar D, Bagga V, Jellinek DA, Chalmers AJ, Carroll TA, Al-Tamimi Y & Collis SJ (2021) O2: TOWARDS A LIVING BIOBANK OF SURGICALLY-RELEVANT 3-DIMENSIONAL GLIOBLASTOMA STEM CELL MODELS TO EVALUATE NOVEL THERAPEUTICS AND INTERROGATE INTRATUMOURAL HETEROGENEITY. British Journal of Surgery, 108(Supplement_1).
(2021) SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study. British Journal of Surgery, 108(9), 1056-1063.
Nepogodiev D, Simoes JFF, Li E, Picciochi M, Glasbey JC, Baiocchi G, Blanco‐Colino R, Chaudhry D, AlAmeer E, El‐Boghdadly K , Wuraola F et al (2021) Timing of surgery following SARS‐CoV‐2 infection: an international prospective cohort study. Anaesthesia, 76(6), 748-758.
Carmell N, Rominiyi O, Myers KN, McGarrity-Cottrell C, Vanderlinden A, Lad N, Perroux-David E, El-Khamisy SF, Fernando M, Finegan KG , Brown S et al (2021) Identification and validation of ERK5 as a DNA damage modulating drug target in glioblastoma. Cancers, 13(5). View this article in WRRO
Rominiyi O, Vanderlinden A, Clenton SJ, Bridgewater C, Al-Tamimi Y & Collis SJ (2021) Tumour treating fields therapy for glioblastoma : current advances and future directions. British Journal of Cancer, 124, 697-709. View this article in WRRO
COVIDSurg Collaborative (2021) Preoperative nasopharyngeal swab testing and postoperative pulmonary complications in patients undergoing elective surgery during the SARS-CoV-2 pandemic.. British Journal of Surgery, 108(1), 88-96. View this article in WRRO
McLean KA, Kamarajah SK, Chaudhry D, Gujjuri RR, Raubenheimer K, Trout I, AlAmeer E, Creagh-Brown B, Harrison EM, Nepogodiev D , Roslani AC et al (2021) Death following pulmonary complications of surgery before and during the SARS-CoV-2 pandemic. British Journal of Surgery, 108(12), 1448-1464.
Glasbey JC, Nepogodiev D, Simoes JFF, Omar O, Li E, Venn ML, PGDME , Abou Chaar MK, Capizzi V, Chaudhry D , Desai A et al (2021) Elective Cancer Surgery in COVID-19–Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study. Journal of Clinical Oncology, 39(1), 66-78.
Fountain D, Piper R, Poon M, Solomou G, Brennan PM, Chowdhury Y, Colombo F, Elmoslemany T, Ewbank F, Grundy P , Hasan MT et al (2020) COVD-15. COVIDNEUROONC: A UK MULTI-CENTRE, PROSPECTIVE COHORT STUDY OF THE IMPACT OF THE COVID-19 PANDEMIC ON THE NEURO-ONCOLOGY SERVICE. Neuro-Oncology, 22(Supplement_2), ii23-ii24.
Glasbey JC, Nepogodiev D, Omar O, Simoes JFF, Ademuyiwa A, Fiore M, Minaya-Bravo A, Shaw R, Vidya R, Bhangu A , Glasbey JC et al (2020) Delaying surgery for patients with a previous SARS-CoV-2 infection. British Journal of Surgery, 107(12), e601-e602. View this article in WRRO
Price SJ, Joannides A, Plaha P, Afshari FT, Albanese E, Barua NU, Chan HW, Critchley G, Flannery T, Fountain DM , Mathew RK et al (2020) Impact of COVID-19 pandemic on surgical neuro-oncology multi-disciplinary team decision making: a national survey (COVID-CNSMDT Study). BMJ Open, 10(8). View this article in WRRO
Rominiyi O, Myers K, Vanderlinden A, Dar D, Bagga V, Gomez-Roman N, Jellinek D, Carroll T, Chalmers A, Al-Tamimi Y & Collis S (2019) TMOD-39. EX-VIVO 3-DIMENSIONAL MODELS OF POST-SURGICAL RESIDUAL DISEASE IN HUMAN GLIOBLASTOMA. Neuro-Oncology, 21(Supplement_6), vi271-vi271.
Rominiyi O, Myers K, Gomez-Roman N, Lad N, Dar D, Jellinek D, Chalmers A, Carroll T, Chen B, Al-Tamimi Y & Collis S (2019) RDNA-12. THE FANCONI ANAEMIA (FA) PATHWAY AND GLIOBLASTOMA: A NEW FOUNDATION FOR DNA DAMAGE RESPONSE TARGETED COMBINATIONS. Neuro-Oncology, 21(Supplement_6), vi209-vi209.
Mohan M, Islim AI, Rasul FT, Rominiyi O, deSouza R-M, Poon MTC, Jamjoom AAB, Kolias AG, Woodfield J, Patel K , Chari A et al (2019) Subarachnoid haemorrhage with negative initial neurovascular imaging: a systematic review and meta-analysis. Acta Neurochirurgica, 161(10), 2013-2026. View this article in WRRO
Rominiyi O, Al-Tamimi Y & Collis SJ (2019) The ‘Ins and Outs’ of Early Preclinical Models for Brain Tumor Research: Are They Valuable and Have We Been Doing It Wrong?. Cancers, 11(3). View this article in WRRO
Rominiyi O, Gomez-Roman N, Lad N, Al-Tamimi Y, Jellinek DA, Chalmers AJ, Carroll TA, Chen B & Collis SJ (2018) P04.74 Preclinical evaluation of combinations targeting the DNA damage response in 2D and 3D models of glioblastoma stem cells. Neuro-Oncology, 20(suppl_3), iii297-iii297.
Ma R, Chari A, Brennan PM, Alalade A, Anderson I, Solth A, Marcus HJ, Watts C, Kolias A, Sinha R , O’Neill K et al (2018) Residual enhancing disease after surgery for glioblastoma: evaluation of practice in the United Kingdom. Neuro-Oncology Practice, 5(2), 74-81.
Rominiyi O, Broman DM, Rajaganeshan R & Selvasekar CR (2011) Colon cancer presenting with polymyositis—A case report. International Journal of Surgery Case Reports, 2(7), 225-227.
Jones CG, Vanderlinden A, Rominiyi O & Collis SJ () Development and Optimisation of Tumour Treating Fields (TTFields) Delivery within 3D Primary Glioma Stem Cell-like Models of Spatial Heterogeneity. Cancers, 16(5), 863-863.
Vanderlinden A, Jones CG, Myers KN, Rominiyi O & Collis SJ () DNA damage response inhibitors enhance tumour treating fields (TTFields) potency in glioma stem-like cells. British Journal of Cancer.
Williams ST, Wells G, Conroy S, Gagg H, Allen R, Rominiyi O, Helleday T, Hullock K, Pennington CEW, Rantala J , Collis SJ et al () Precision oncology using ex vivo technology: a step towards individualised cancer care?. Expert Reviews in Molecular Medicine, 1-48.
Richardson GE, Islim AI, Albanese E, Ahmed A, Aly A, Ammar A, Amoo M, Bhatt H, Bodkin P, Coulter I , Corr P et al () Neurosurgery activity levels in the United Kingdom and republic of Ireland during the first wave of the covid-19 pandemic – a retrospective cross-sectional cohort study. British Journal of Neurosurgery, 1-6.
Bravo L, Nepogodiev D, Glasbey JC, Li E, Simoes JFF, Kamarajah SK, Picciochi M, Abbott TEF, Ademuyiwa AO, Arnaud AP , Agarwal A et al () Machine learning risk prediction of mortality for patients undergoing surgery with perioperative SARS-CoV-2: the COVIDSurg mortality score. British Journal of Surgery.
Hardman S, Rominiyi O, King D & Snelson E () Is cranial computed tomography unnecessary in children with a head injury and isolated vomiting?. BMJ, l1875-l1875.

Conference proceedings papers

Ooi SZY, Dada OE, Bukenya GW, Kenfack YJ, Chi L, Ohonba E, Adeyemo E, Narain K, Awad AK, Barrie U , Sichimba D et al (2022) O021 Evaluating the impact of neurosurgical rotation experience in Africa on the interest and perception of medical students towards a career in neurosurgery: a continental, multi-centre, cross-sectional study. British Journal of Surgery, Vol. 109(Supplement_4)
Dada OE, Ooi SZY, Bukenya GW, Kenfack YJ, Le C, Ohonba E, Adeyemo E, Narain K, Awad AK, Barrie U , Sichimba D et al (2022) 814 Evaluating the Impact of Neurosurgical Rotation Experience in Africa on the Interest and Perception of Medical Students Towards a Career in Neurosurgery: A Continental, Multi-Centre, Cross-Sectional Study. BRITISH JOURNAL OF SURGERY, Vol. 109(SUPPL 6)
McGarrity-Cottrell C, Myers K, Wang D, Dunning M, Bagga V, Al-Tamimi Y, Sinha S, Rominiyi O & Collis S (2022) GENERATION AND CHARACTERISATION OF A LIVING BIOBANK OF POST-SURGICAL RESIDUAL GLIOBLASTOMA TO IDENTIFY NOVEL THERAPEUTIC TARGETS.. NEURO-ONCOLOGY, Vol. 24 (pp 31-31)
Vanderlinden A, Rominiyi O, Collis S, Jones C, Myers K & McGarrity-Cottrell C (2022) COMBINING TUMOUR TREATING FIELDS WITH THERAPEUTIC DNA DAMAGE RESPONSE INHIBITORS TO INCREASE POTENCY IN HIGH-GRADE GLIOBLASTOMAS USING CLINICALLY RELEVANT EX-VIVO GLIOMA STEM CELL MODELS.. NEURO-ONCOLOGY, Vol. 24 (pp 93-93)
Gagg H, Williams S, Allen R, Conroy S, Rominiyi O, Wells G, Rantala J, Danson S, Helleday T & Collis S (2022) Ex vivo-led drug discovery in glioblastoma. WFNOS 2022 Abstract Book (pp s240)
Wedderburn Z, Anim-Boadu R, Choudhari K, Mezei G, Ushewokunze S, Zaki H, Bagga V, McMullan J, Sinha S, Al-Tamimi Y & Rominiyi O (2022) Does socioeconomic status influence the survival of patients undergoing surgery for newly-diagnosed glioblastoma? A 5-year review of deprivation indices and outcomes across South Yorkshire, United Kingdom. WFNOS 2022 Abstract Book (pp s197)
Rominiyi O, Myers K, Gomez-Roman N, Jellinek DA, Chalmers AJ, Carroll TA, Chen B, Al-Tamimi Y & Collis S (2022) Combined inhibition of the Fanconi anaemia (FA) pathway and ATR promotes R-loop generation and profound radiosensitisation in glioblastoma. WFNOS 2022 Abstract Book (pp s253)
Rominiyi O, Vanderlinden A, Clenton SJ, Bridgewater C, Al-Tamimi Y & Collis S (2022) Tumour treating fields (TTFields) therapy for glioblastoma: a quantitative and qualitative summary of research and advances in our understanding. WFNOS 2022 Abstract Book (pp s251)
Zizzo C, Keating J, Sinha S, Al-Tamimi Y, Dyson B, Collis S & Rominiyi O (2022) Patient-centric design of a neuro-oncology research primer to enhance communication and support of specimen donation for preclinical research. WFNOS 2022 Abstract Book (pp s65)
Vanderlinden A, McGarrity-Cottrell C, Myers K, Carroll TA, Al-Tamimi Y, Rominiyi O & Collis S (2022) DNA damage response inhibitor combinations to enhance TTFields potency using clinically relevant ex-vivo glioblastoma models. WFNOS 2022 Abstract Book (pp s227-s221)
Cottrell CM, Myers K, Dunning M, Bagga V, Sinha S, Al-Tamimi Y, Wang D, Rominiyi O & Collis S (2022) Development of unique ex vivo models of post-surgical residual glioblastoma. WFNOS 2022 Abstract Book (pp s219)
Fountain D, Piper R, Poon M, Solomou G, Brennan PM, Chowdhury Y, Colombo F, Elmoslemany T, Ewbank F, Grundy P , Hasan MT et al (2020) COVIDNEUROONC: A UK MULTI-CENTRE, PROSPECTIVE COHORT STUDY OF THE IMPACT OF THE COVID-19 PANDEMIC ON THE NEURO-ONCOLOGY SERVICE. NEURO-ONCOLOGY, Vol. 22 (pp 23-24)
Rominiyi O, Myers K, Vanderlinden A, Dar D, Bagga V, Gomez-Roman N, Jellinek D, Carroll T, Chalmers A, Al-Tamimi Y & Collis S (2019) EX-VIVO 3-DIMENSIONAL MODELS OF POST-SURGICAL RESIDUAL DISEASE IN HUMAN GLIOBLASTOMA. NEURO-ONCOLOGY, Vol. 21 (pp 271-271)
Rominiyi O, Myers K, Gomez-Roman N, Lad N, Dar D, Jellinek D, Chalmers A, Carroll T, Chen B, Al-Tamimi Y & Cellis S (2019) THE FANCONI ANAEMIA (FA) PATHWAY AND GLIOBLASTOMA: A NEW FOUNDATION FOR DNA DAMAGE RESPONSE TARGETED COMBINATIONS. NEURO-ONCOLOGY, Vol. 21 (pp 209-209)
Rominiyi MO, Gomez-Roman DN, Al-Tamimi MY, Jellinek MDA, Chalmers PAJ, Carroll MTA, Chen PB & Collis DS (2018) FA-based combinations to target the DNA damage response in glioblastoma. Neuro-Oncology, Vol. 20(suppl_5) (pp v358-v358). Winchester, UK, 4 July 2018 - 6 July 2018. View this article in WRRO
Rominiyi O, Gomez-Roman N, Lad N, Al-Tamimi Y, Jellinek DA, Chalmers AJ, Carroll TA, Chen B & Collis SJ (2018) PRECLINICAL EVALUATION OF COMBINATIONS TARGETING THE DNA DAMAGE RESPONSE IN 2D AND 3D MODELS OF GLIOBLASTOMA STEM CELLS. NEURO-ONCOLOGY, Vol. 20 (pp 297-297)

Preprints

Birch J, Strathdee K, Stevenson K, Derby S, Dutton L, Clough E, Koessinger A, Gilmour L, McGhee E, McGarrity-Cottrell C , Dibekeme AA et al () Inhibition of ATR prevents macropinocytosis driven retraction of neurites and opposes invasion in GBM, Research Square Platform LLC.

Research group

As part of the newly established Sheffield Translational Brain Tumour Research Group, I work in close collaboration with Dr Spencer Collis (Scientific Lead) and Mr Yahia Al-Tamimi (Clinical Lead) as the Group’s Translational Lead to help drive forward a number of projects.

Postgraduate Students as Primary Supervisor
Kelsey Wosnitzka (PhD Student)
Claudia Zizzo (MSc Science Communication)

As Secondary/Tertiary Supervisor
Aurelie Vanderlinden Dibekeme (PhD student)
Connor McGarrity-Cottrell (PhD student)
Hannah Gagg (PhD student)
Andra-Gabriela Antohi (MRes student)

Post-Doctoral Researchers
Dr Katie Myers (PDRA & Genome Stability Group Lab Manager) – with Dr Collis
Dr Callum Jones (PDRA) – with Dr Collis

Grants: American Association for Cancer Research (AACR)
GE Healthcare UK
National Centre for the Replacement Refinement & Reduction of Animals in Research (NC3Rs)
National Institute for Health Research (NIHR)
Neurocare
Novocure
Royal College of Surgeons (RCS)
Sheffield Hospitals Charity (SHC)
Sheffield NIHR Biomedical Research Centre (BRC)
Tenovus Scotland
The Brain Tumour Charity (TBTC)
Weston Park Cancer Charity (WPCC)
Yorkshire’s Brain Tumour Charity (YBTC)

Teaching interests

Neuro-oncology and the DNA damage response
Clinical Neurosurgery

Professional activities and memberships

2020-2021+ NIHR Surgical Translational Research Collaborative – Sheffield Representative.

2018-2021+ Lead in TUoS ‘Industry-Academia’ collaboration with Novocure (TTFields).

2017-2021+ Lead for 100,000 Genomes Project Neuro-Oncology Recruitment & Data Curation at STH.

2017-2021+ Frequent reviewer for the British Journal of Neurosurgery, Cancer Biology & Medicine, British Journal of Cancer.

2016-2021+ Lead for Patient-Derived Glioblastoma Sample Retrieval at STH.

Current Projects

TRANSLATIONAL

A. Advancing DNA damage response (DDR) targeted therapeutic combinations using surgical delivery

Robust data from my PhD studies reveals that simultaneous inhibition of FA pathway and PARP or ATR represents a highly efficacious approach to eliminate treatment-resistant glioblastoma stem cells. However, numerous compounds used to target these key DDR processes demonstrate poor penetration of the blood-brain barrier. I am therefore seeking funding to investigate the post-surgical intracavity delivery of our DDR-targeted combinations within a thermo-responsive, long-lasting, biodegradable paste in collaboration with Dr Ruman Rahman & Mr Stuart Smith (University of Nottingham) (https://doi.org/10.1158/1078-0432.CCR-18-3850).

B. Understanding and overcoming treatment resistance in glioblastoma stem cells

Working in close partnership with Dr Spencer Collis (University of Sheffield), we are currently investigating the following therapeutic approaches.

B1 – Ex vivo 3D models of post-surgical residual disease to improve biological understanding and treatment: These studies aim to characterise the specific nuances of disease typically left-behind after surgery and identify an ‘Achilles heel’ of residual disease to help ensure future therapies can effectively eradicate post-surgical disease (https://www.thebraintumourcharity.org/brain-tumour-diagnosis-treatment/types-of-brain-tumour-adult/glioblastoma/glioblastoma-research/new-3d-models-invading-glioblastoma/). We are also developing these surgically-relevant models as a replacement for animal studies in certain contexts (https://nc3rs.org.uk/living-biobank-post-surgical-residual-glioblastoma-replace-animal-studies).

B2 – Ex vivo drug screening using human tissue to personalise cancer therapy: In collaboration with Professor Thomas Helleday (Karolinska Institutet), Dr Juha Rantala (Misvik Biology, CEO - https://www.misvik.com), Dr Greg Wells (Ex vivo Drug Screening Lead, Weston Park Cancer Centre), Professor Sarah Danson (Sheffield CRUK ECMC and ex vivo Clinical Lead) and Allcyte (https://www.allcyte.com), I aim to ensure these technologies, which use ultra-high content microscopy of freshly dissociated tumour tissue to prioritise the clinical potential of over 260 approved and experimental compounds, are applied to benefit patients with high-grade brain tumours (https://nc3rs.org.uk/ex-vivo-drug-screening-using-human-tissue-personalise-cancer-therapy-and-replace-murine-avatars).

B3 – Combining TTFields with therapeutic DDR inhibitors for the improved treatment of brain tumours: In collaboration with Novocure, we are developing more effective combination treatments based on TTFields therapy, which uses low-intensity, intermediate frequency alternating electrical fields to treat cancer and has been demonstrated to increase overall survival for patients with newly-diagnosed glioblastoma in a Phase III clinical trial (https://doi.org/10.1001/jama.2017.18718).

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Figure: Summary of the mechanisms of action of TTFields.

From Rominiyi O & Vanderlinden A et al. Tumour treating fields therapy for glioblastoma: current advances and future directions. British Journal of Cancer (2021) 124(4):697-709 (https://doi.org/10.1038/s41416-020-01136-5).

B4 – Development of novel inhibitors of the FA pathway (nFAPi) to treat brain cancer: I also support Dr Spencer Collis, Professor Beining Chen (Department of Chemistry, University of Sheffield) and Mr Thomas Carroll (Sheffield Teaching Hospitals NHS Foundation Trust) in the development of potent, highly-selective compounds which inhibit FA pathway activity and have the potential to enhance the effectiveness of chemotherapy and radiotherapy in high-grade glioma.

B5 – Dissecting spatiofunctional heterogeneity in the DNA damage response of glioblastoma: These studies aim to leverage advanced surgically-relevant models of glioblastoma with detailed spatial characterisation to better understand regional differences in responses to DNA damaging therapy at the molecular level and develop therapeutic strategies able to tackle this biological complexity.

Collectively, leveraging data on the most attractive therapeutic targets from these studies and our continually expanding Living Biobank of surgically-relevant, patient-specific glioblastoma stem cell models, we aim to work towards the establishment of strong academic collaborations and future industrial partnerships with pharmaceutical companies to help prioritise the translation of novel compounds. We are always pleased to consider proposals to collaborate and discuss sharing these resources where this has the potential to advance cancer therapy.

CLINICAL

C. Detecting a ‘Pink Drink’ in the blood as an early warning system for brain tumours – towards Sheffield Monitoring Test (SMT)

These studies aim establish whether protoporphyrin IX (PpIX), the fluorescent molecule used to improve surgical resection rates for glioblastoma intra-operatively after administering 5-ALA (the ‘pink drink’), can also be detected in the blood to provide a tumour marker for glioblastoma which quantitatively reflects tumour burden.

D. Developing a ‘Phase 0’ neurosurgical clinical trial capability in Sheffield

‘Phase 0’ neurosurgical clinical trials (https://doi.org/10.1093/neuros/nyz218), where a drug is administered pre-operatively then resected tumour tissue assessed in the laboratory to quantify drug concentration and target effects represent an extremely valuable and underutilized pragmatic tool to confirm whether or not potential anti-cancer drugs are able to sufficiently cross the blood-brain/blood-tumour barrier. We are actively seeking funding to establish this capability in Sheffield and help ensure therapeutic approaches, including those developed by our team, have a clear route towards the clinic. The establishment of a Phase 0 / ‘window of opportunity study’ capability will be well supported by Sheffield’s growing capability to support fulfilment of the translational pathway including through the Early Phase Initiative (EPI) and Sheffield’s status as a CRUK Experimental Cancer Medicine Centre (ECMC).

I am pleased to consider applications / expressions of interest from prospective PhD students.