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Welcome to our lab

The Robson Lab was established by Prof. Tracy Robson in 2004 in the School of Pharmacy, Queen’s University of Belfast, Northern Ireland. In 2016, following Prof. Robson’s appointment as Head of Department, the Robson Lab moved to the Department of Molecular and Cellular Therapeutics (MCT), at RCSI University of Medicine and Health Sciences, Dublin, Ireland. In 2019 MCT merged with the former School of Pharmacy to form the new and innovative School of Pharmacy and Biomolecular Sciences, where Prof. Robson is Head of School. Our lab is based in newly refurbished molecular biology labs, with state-of-the-art facilities in RCSI building 123 St. Stephen’s Green.

The Robson Lab is part of the Irish Centre for Vascular Biology  and the National Children’s Research Centre.

Our lab comprises of numerous research themes with a common focus on the biology of a protein called FK506 Binding Protein Like (or FKBPL). Overall, our aim is to understand and harness the known protective anti-inflammatory and anti-cancer effects of FKBPL to therapeutically treat a whole plethora of conditions, including cancer, vascular disease, inflammatory disorders and obesity.

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Research

For the past 15 years the Robson Lab has focused it’s entire research efforts on elucidating the biological role of a novel protein called FK506 Binding Protein Like (or abbreviated to FKBPL).

FKBPL is a member of a family of proteins known as immunophilins. Immunophilins are characterised by the presence of a prolyl isomerases (PPIase) and in the case of larger protein family members the additional presence of a tetratricopeptide repeat (TPR) domain. However FKBPL is divergent member of this family with shared homology only in the C-terminal TPR domain which is important for the interactions with the chaperone protein Hsp90, involved in protein folding.

Early research from the Robson lab revealed that FKBPL, and in particular it’s N-terminal region, had anti-angiogenic activity, i.e. it could inhibit the formation of new blood vessels. Angiogenesis is critical to the sustained growth of a tumour, and thus a unique opportunity to develop a new anti-cancer therapy arose. In collaboration with Almac Discovery, a peptide therapeutic (AD-01) was developed and it was found to robustly inhibit vessel formation in murine models. Following further pharmacokinetic testing, a next generation peptide was developed coined ALM201. Both AD-01 and ALM201 massively reduced tumour volume and the number of blood vessels in the tumour mass of murine xenograft models. Importantly the therapeutic peptides did not indicate any toxicity in the models tested.

Fig.2: Development of a biological FKBPL peptide. A 24 mer was synthesised (AD-01) which robustly inhibited vessel formation in mouse models.  Following deletion of a single glutamine residue, a 23 mer (ALM201) was synthesised and became the peptide of choice for clinical testing.

Following promising preclinical work, ALM201 completed a Phase I trial that was published in 2017, with the primary aim of checking safety and identifying phase II dose. Importantly the drug was well tolerated by patients and no dose limiting toxicities were recorded (NCT03427073).

In addition to being found in the cytoplasm, FKBPL is also secreted from numerous cell types, including endothelial cells, immune cells and cancer cells. In addition to it’s anti-angiogenic role, full length FKBPL protein and it’s therapeutic peptide mimetics have been shown to regulate cancer stem cell differentiation, and most recently it has been shown to have a role in inflammation and obesity, and these are now major research themes within the Robson Lab.

Fig. 3 FKBPL has been shown to have a protective role in cancer, obesity, and inflammation, indicating it’s far reaching therapeutic implications to treat numerous conditions.

Recently the Robson Lab have been investigating alternative therapeutic strategies to deliver full length FKBPL into cells to overcome possible limitations with peptide based therapies such as the potentially truncated activity of the protein. These investigations, in collaboration with pHion Therapeutics, involve complexing the FKBPL gene (pFKBPL) with an amphipathic peptide called RALA, to form a nanoparticle, which we have shown to strongly inhibit angiogenesis and subsequent tumour growth in mouse xenograft models.

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Meet the Team

Professor Tracy Robson

Principal Investigator & Head of School

Tracy Robson obtained her PhD in Cancer Biology from Imperial College, London. Her first academic post was as Lecturer in Radiation Science at Ulster University in 1997; she was promoted to Reader in 2001. She then moved to the School of Pharmacy, Queen’s University of Belfast in 2004 to take up the post of Reader in Molecular Pharmacology; she was promoted to Professor in 2010. In 2016, she took up position as Professor and Head of Department of Molecular and Cellular Therapeutics at RCSI. In 2019 following the merging of MCT and School of Pharmacy, she became Head of the School of Pharmacy and Biomolecular Sciences. Her major focus was the development of novel approaches for sensitizing tumours to therapy using personalised medicine approaches.  She led a major programme of research aimed at the identification and functional characterisation of genes that alter tumour response to anti-cancer agents.  In particular, she cloned and characterized a novel human gene, FKBPL. Her group has demonstrated an extracellular role for FKBPL as a naturally secreted, anti-angiogenic protein. Together with Almac, she led the development of therapeutic peptide derivatives (AD-01 and ALM201) based on FKBPL’s active anti-angiogenic domain. Based on the robust efficacy and excellent safety profile, ALM201, a ‘first-in-class’ FKBPL-based anti-angiogenic therapeutic peptide has completed formulation and toxicology testing and has entered phase I/II cancer clinical trials (EudraCT number: 2014-001175-31).  More recently, ALM201 was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) in the treatment of ovarian cancer. More recently, through the development of genetically modified mouse models, she has also demonstrated a role for FKBPL in protection against obesity, with FKBPL deficient mice becoming severely obese. Like cancer, obesity is associated with vascular regulation and inflammation.Her research is now focussing on unravelling the associated mechanisms driving FKBPL’s protective activity in obesity and obesity –induced cancer so that the clear translational potential of FKBPL-based therapeutics can be fully harnessed and FKBPL’s diagnostic potential in these disease settings can be scrutinized.

 

Current Researchers

Dr. Stephanie Annett, POSTDOCTORAL RESEARCHER & HONORARY LECTURER

Dr. Gillian Moore, postdoctoral researcher & Honorary Lecturer

Gillian Moore (PhD) obtained a first class honours B.A. (mod) in Molecular Medicine from the School of Biochemistry and Immunology, Trinity College Dublin in 2012. It was during this time that she developed a keen interest in cancer research.  She went on to be awarded an Irish Research Council PhD scholarship to carry out a her PhD thesis research entitled ” Exploring the role of lipoxygenases in oesophageal cancer and the anti-angiogenic potential of novel lipoxygenase inhibitors”, in the Department of Surgery, Trinity Translational Medicine Institute (TTMI), St. James’ Hospital Dublin. After graduating in 2016, Gillian carried out a post-doctoral research project in the Thoracic Oncology Research Group, based in the Department of Clinical Medicine, TTMI, where she investigated novel mechanisms of resistance to PI3K/mTOR inhibitor therapies in lung cancer. Gillian then joined the Robson Lab in 2017, where she is carrying out research to further unravel the cancer biomarker potential of FKBPL and the mechanism of action of the FKBPL-based drug therapeutic, ALM201, developed by the Robson Lab, in collaboration with Almac Discovery. 

Gillian’s research interests include biomarker discovery, personalized medicine, novel small molecule and biological therapeutic strategies for the treatment of cancer, tumour-associated angiogenesis and stemness. 

Email: gillianmoore@rcsi.com

Twitter: @GillMooreBirch

Previous rESEARCHERS

Aisling O’Hagan 

Charlotte Mallindine 

Jamie Arkley 

Sharon Potts 

Meabh Cassidy 

John Conor Doyle 

Rachel Lennox

Rami Abu Mousa 

Ahmed Salah Elmasoudi

Amy Slater

Margaret Murray, PhD 

Jenny Worthington, PhD 

Stephen Moore, PhD

Marie McIlroy, PhD 

Hayley McKeen, PhD

Karl Butterworth, PhD

Sheila Young, PhD

Catharine Adams, PhD

Jonathan Coulter, PhD

Kerry McAlpine, PhD

Keeva McClelland, PhD

Christopher Byrne, PhD 

Hayder Dyer, PhD

Kim Cherry, PhD

Alek Zholobenko, PhD

Christopher Donley, PhD

Nuala Mulgrew, PhD

Wendy Hyland, PhD

Ahlam Ali, PhD

Ashley Davison, PhD

Lana McClements, PhD

Chris Armstrong, PhD

Rachel Bennett, PhD

Laura Nelson, PhD

John McBride, PhD

Tara Byrne, PhD

Amy Short, PhD

Nermeen Moustafa, PhD 

Shannon O’Neill, PhD

Hannah Thompson, PhD

Phil Chambers, PhD

Cian McCrudden, PhD

Anita Yakkundi, PhD

Lynn McCallum, PhD 

Andrea Valentine, PhD

Martin O’Rourke, PhD

Claire Murphy, PhD

George Burke, PhD

Helen McCarthy, PhD, Prof

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