51cg

Biography

I studied preclinical medicine at St Andrews University before completing my clinical training and undertaking my PhD at Cambridge University. Following this I moved to the University of Edinburgh to train as a pathologist and was appointed as a SCREDS clinical lecturer in 2018. Following the completion of my specialist training in pathology, in 2022, I took up a Consultant post in the Department of Pathology in Aberdeen alongside a Senior Lecturer post, and was appointed to Clinical Chair in 2024.

My research focuses on the molecular mechanisms underlying neurodegenerative diseases with a particular focus on ALS. The work in my lab involves studying patient samples (tissue and biofluids) for molecular differences that could explain why people with ALS have such diverse symptoms, including differences in disease progression and cognitive involvement. The aim of our work is to identify targets that could be used for diagnosis or to monitor disease progression, or ultimately, for therapies to improve the outlook for people with ALS.

Have a look at our lab website for up to date news, information about our group members, and a description of our ongoing projects:

Research Overview

Our lab searches for the earliest indicators of motor neurone disease/ALS in non-central nervous system tissues, particularly the digestive tract. The aim is to facilitate widespread clinical testing and trigger earlier therapeutic intervention.

Our team:

Dr. Fergal Waldron (Advanced Research Fellow)

Fergal’s research examines factors that influence disease heterogeniety in ALS with special focus on the role of inflammation and immune pathways. His work involves a combination of experimental, bioinformatics and evidence synthesis approaches to answer fundamental questions in ALS research.

Fergal obtained his PhD in Evolutionary Genetics from the University of Cambridge before undertaking postdoctoral work at the Institute of Evolutionary Biology at the University of Edinburgh. His past research has focused on the evolutionary genetics of antiviral immunity in invertebrate animal models, and the evolution of antiviral immunity across invertebrates. /people/fergal.waldron#about

Dr. Holly Spence (Research Fellow)

Holly’s research focuses on the physical biology of neurodegeneration in Amyotrophic Lateral Sclerosis and Frontotemporal dementia.

Holly completed her PhD in Medical Sciences at 51cg investigating the role of brain iron in age-related cognitive decline and exploring the relationships between brain iron and blood markers for iron and inflammation.

Current Research

Understanding the extra-motor manifestations of ALS

Many people living with motor neuron disease will experience cognitive dysfunction during their disease. In fact, motor neuron disease is now considered part of the same disease spectrum of frontotemporal dementia, characterised by cognitive dysfunction in behaviour, language, fluency and executive functioning. Our group have created several deeply-phenotyped post-mortem tissue cohorts to try to understand what makes some people more susceptible to these non-motor/cognitive symptoms, something that we hope will allow us to open therapeutic avenues for susceptible individuals in the future. Our group are also interested in non-central nervous system manifestations of motor neuron disease. Non-neurological symptoms are common in people with motor neuron disease, and we showed recently that the same pathology that is seen in the brain at post-mortem can be seen in non-central nervous system tissues (particularly gut tissues) many years prior to motor or cognitive symptom onset. This could provide us with a biomarker for early diagnosis and possibly even improve chances for early therapeutic intervention.

Inflammation & molecular crowding in ALS

One of the unifying pathological features in the majority of neurodegenerative diseases is the presence of aberrantly misfolded intra- and extra-cellular protein aggregates. These aggregates are present in the central nervous system at post-mortem, but our group was the first to show that these aggregates are also present in non-CNS tissues many years prior to neurological symptom onset in motor neuron disease. We are interested in common pathomechanisms that could be driving this aggregation in different CNS and non-CNS organs. Our central hypothesis for this work is that aggregation and cellular dysfunction is precipitated by crowding of the intracellular environment potentiating the aggregation of aggregation-prone proteins and preventing their disassembly. We believe that this could be potentiated by extrinsic pressure on cells, caused by inflammation and extracellular oedema, constricting their environment resulting in compression that reduces cell volume. Indeed, we see distinct inflammatory activation signatures in sequencing data from motor neuron disease patients. Our group is interested in investigating specific mechanisms of inflammation and understanding how these mechanisms could be manipulated therapeutically.

Translational Medicine

As a clinician scientist, I am keen to facilitate the translation of experimental science to the clinic. As part of this research theme, our group regularly perform systematic-reviews and meta-analyses, spanning a wide range of clinical questions, including evaluations of both the preclinical and clinical literature. Data quality assessments and research recommendations are also an integral part of our approach. Examples of previous projects are listed below. This research is particularly useful for undergraduates (clinical and non-clinical), PhD students and early career researchers who want to gain a better understanding of a particular research topic and often results in high-value translational publications. We often have projects ongoing in this area and are happy to design new bespoke projects for individuals to lead on, so get in touch if you are interested.

Knowledge Exchange

Our group are involved with the LEARN (lived experience and researcher network) a patient engagement initiative run through MND Scotland.

Have a look at some of our recent patient advocacy engagement work:

Collaborations

Dr. Neil Shneider (Columbia University/Elanour & Lou Gerrig ALS Centre)

Dr. Mathew Horrocks (University of Edinburgh)

Prof. Gian Gaetano Tartaglia (Italian Institute of Technology, Genoa)

Dr. Elsa Zacco (Italian Institute of Technology, Genoa) 

Prof. Liam Holt (New York University)

Dr. Hemali Phatnani (New York Genome Centre)

Prof. Ai Yamamoto (Columbia University)

Prof. Sharon Abrahams (University of Edinburgh)

Prof. Pietro Fratta (University College London)

Prof. Paul Fowler (51cg)

Prof. Cord Langner (Medical University of Graz, Institute of Pathology)

Dr. James Longden (e-therapeutics PLC, Edinburgh)

Funding and Grants

Medical Research Council Equipment Grant – “NanoString Integrated Spatial Biology Platform”: £610,839(2023)Award to PI Jenna Gregory, and co-investigators Paul Fowler (51cg), Elaina Collie-Duguid (51cg), Gillian Milne (51cg) and Kristine Nellany (NHS Grampian).

Target ALS Foundation Award: $1,000,000(2022 – 2024)Award to Jenna Gregory as one of four PIs with $250 K direct costs award to the Gregory lab. Collaborative grant with Mathew Horrocks (Edinburgh University), Neil Shneider (Columbia University), Elsa Zacco (Italian Institute of Technology, Genoa) and Gian Gaetano Tartaglia (Italian Institute of Technology, Genoa).

Motor Neurone Disease Association Grant: £200,000(2022 – 2024)Award to Jenna Gregory as one of 4 PIs with £10 K direct costs award to the Gregory lab. Collaborative grant with lead PI Valeria Gerbino (Fondazione Santa Lucia, Rome), Tom Manniatis (Columbia University), and Jemeen Sreedharan (King’s College London).

MND Scotland Research Award: £75,000(2022 – 2024)Award to Jenna Gregory (PI)

Royal Society Small Grant Scheme: £20,000(2022 – 2023)Award to Jenna Gregory (PI)

NIH Transformative Research Award (TRO1): $8,400,000(2021 – 2026)Award to Jenna Gregory as one of four PIs with $1.2M direct costs award to Gregory lab. Collaborative grant with Liam Holt (New York University) and Hemali Phatnani & Ai Yamamoto (Columbia University).

Chan Zuckerberg Initiative Neurodegeneration Challenge Network (CZI-NDCN) Collaborative Supplement: $60,000(2021 – 2022)Award to Jenna Gregory one of four PIs. Collaborative grant with Michael Ward (NIH), Pietro Fratta (UCL) and Hemali Phatnani (Columbia University).

Pathological Society Equipment Grant: £7,000(2020 – 2021)Award to Jenna Gregory (PI)

Jean Shanks Foundation and Pathological Society Clinical Lecturer Support Grant: £100,000(2020 – 2022)Award to Jenna Gregory (PI)

Scottish Universities Life Sciences Alliance (SULSA) Travel Award: £5,000(2019)Award to Jenna Gregory (PI)

Edinburgh Neuroscience RS MacDonald Seedcorn Fund: £5,000(2018 – 2019)Award to Jenna Gregory (PI)

Academy of Medical Sciences (AMS) Starter Grants for Clinical Lecturers: £29,435(2018 – 2019)Award to Jenna Gregory (PI)

Academic Trainee Research Support (Division of Pathology, University of Edinburgh): £1,000(2018 – 2019)Award to Jenna Gregory (PI)

Pump-priming Pathology Endowment Fund (Division of Pathology, University of Edinburgh): £2,000(2018 – present)Award to Jenna Gregory (PI)