Mateusz W. Kucharczyk, Ph.D., principal investigator

Head of Cancer Neurophysiology Research Group at Łukasiewicz – PORT, Wrocław, Poland
Visiting Research Fellow, Wolfson Sensory, Pain, and Regeneration Centre, King’s College London, London, UK

Mateusz earned Biotechnology degrees (BSc, MSc) from Jagiellonian University in Kraków. As a Marie Skłodowska-Curie trainee, he completed his PhD in Neuroscience at University College London, specialising in in vivo electrophysiology with Professor Anthony Dickenson and in vivo calcium imaging with Professor Stephen McMahon (King’s College London) to study cancer-induced bone pain. After learning optogenetics in Yves De Koninck Lab (Quebec, Canada), he worked as a PDRA in Dr Kirsty Bannister group (King’s College London), where he advanced opto- and chemogenetic techniques for studying descending modulatory circuits in health and disease.

Mat’s X/Twitter: @matwku

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This laboratory bridges Neuroscience with Oncology to investigate a role of the sympathetic and somatosensory systems in neurogenic mechanisms controlling tumorigenesis and related pain.

Cancer Neuroscience

Neuronal pathways travel from the brain to the spinal cord to influence somatosensation. They regulate spinal and primary sensory neuron activity, enabling the brain to finely tune signal levels transmitted through the spinal cord and govern the periphery via neurogenic mechanisms. Importantly, there exists an ongoing dialogue between nerves and tumours. For instance, tumour denervation slows or prevents neoplastic growth. Neuropeptides released by peptidergic nociceptors drive tumour neovascularisation and enhance cancer immunosurveillance. Furthermore, tumours at the early stages are usually not painful. We believe that presynaptic modulation of central sensory endings is the key aspect not only for nociception and pain control, but also other aspects of (patho)physiology. For instance, it can provide a neuroimmune link to the periphery, particularly important in the context of neurogenic control of peripheral immune and neoplastic changes. Since tumours development is regulated by neurogenic events, the control of neuronal activity may lead to development of a novel class of chemotherapeutics.

Perceptual Flexibility, Pain and Nociception

Our brain is a powerful organ, capable of re-interpreting the nature of sensory stimuli. An identical stimulus can appear excruciating or mildly irritating depending on the circumstance, for instance a wound hurts more at home than on a battlefield (Beecher, 1946). At the most fundamental level, this perceptual flexibility is dependent on descending modulatory controls: neural circuits which alter activity of spinal cord projection neurons that integrate all ascending peripheral somatosensory information. Therein, modulation of nociception can be achieved also via the activity of descending brain controls directly acting on primary afferent central terminals. In that way, the brain can ‘gate the level of painful signals’ that are to be passed onto the spinal transmission system². It is the first checkpoint where nociception can be centrally modulated, and hence a very attractive target for analgesia. Additionally, primary afferent central terminals can also be controlled by local spinal circuits that are themselves subject to descending modulation. For technical reasons, presynaptic control of small calibre afferents (nociceptors) has hardly been explored, but they are critical to understanding nociception and neurogenic tumour and immune control. With novel technological approaches, we offer an unprecedented level of biophysical investigation into the function of those afferent terminals with a goal for the development of new painkillers.

Our approach

Employing a combination of high throughput in vivo electrophysiology (i.e. Neuropixels) and calcium imaging (i.e., Miniscopes and 2-photon) with opto- and chemogenetic modulation of genetically and anatomically defined neuronal circuits, we sample the activity of the spinal and peripheral neurons and correlate this activity with behavioural responses using machine learning-supported analysis. We aim to link network-wide neuronal function with top-down ability to influence both nociception and tumorigenesis. Changes in the tumour and its microenvironment are analysed with a state-of-the-art 3D tumour reconstruction using tissue clearing with light-sheet imaging, as well as on a molecular level with cytometry (FACS), RNAseq and high throughput spectroscopy. Our world-wide collaborations offer back and forward translation to clinic with somatosensory testing, MRI/PET, and CT.

Present:

2023 – 2026: Starting Budget, Polish Center for Technology Development (2.9M PLN). ‘Neurogenic mechanisms controlling tumourigenesis”.

Three fully funded positions (1x Postdoc, 1x Lab Manager, 1x Technician).

#cancer neuroscience #noradrenaline #CGRP #NGF #silent nociceptors #cancer pain #neuroimmune #FACS #light-sheet imaging #tissue clearing

2023 – 2026: Sonata 18, National Science Center (Poland) Research Grant (3.49M PLN). ‘Noradrenergic modulation of the central sensory terminals”.

Three fully funded positions (2x Postdoc, 1x PhD student).

#neuroscience #noradrenaline #DPMS #nociception #pain #in vivo electrophysiology #optogenetics #2-photon imaging #pain behaviour #computer vision

Past:

2022 – 2023: National Science Center (Poland) Research Grant (£8,322). ‘Characterisation of somatosensory changes in an animal model of ischemic stroke’

#neuroscience #ischemic stroke #DPMS #nociception #pain #in vivo electrophysiology #pain behaviour

2022: Guarantors of Brain Travel Grant for IASP2022 Pain Congress in Toronto (4.8k PLN)

2022: Improving Racial Diversity and Inclusion at King’s Award (18.8k PLN)

2021: King’s College London Early Career Research Award (12.7k PLN)

2019: Polish National Agency for Academic Exchange Collaboration Grant (7.5k PLN)

2015 – 2018: European Union Marie Skłodowska-Curie PhD Scholarship (690k PLN)

2012 – 2013: Foundation for Polish Science Master Award (12.7k PLN)

2011 – 2012: Jagiellonian University Rector ‘University Top 5%’ Scientific Award (6.5k PLN)

PUBLICATIONS

Research Manuscripts: *corresponding author, ^co-first

A critical brainstem relay for mediation of diffuse noxious inhibitory controls Kucharczyk, MW*, Di Domenico F, Bannister K. Brain, 2023, (preprint: BioRxiv), PMID: 36625030

Distinct brainstem to spinal cord noradrenergic pathways inversely regulate spinal neuronal activity Kucharczyk, MW*, Di Domenico F, Bannister K.
Brain, 2022 (preprint: BioRxiv), PMID: 35245374
Paper selected as Editor’s choice by International Association for the Study of Pain research forum, and covered by King’s College London News.

The stage specific plasticity of descending modulatory controls in a rodent model of cancer induced bone pain Kucharczyk, MW*, Derrien D, Dickenson AH, Bannister K. Cancers (Basel), 2020 (preprint: BioRxiv), PMID: 33172040

Activation of the Descending Pain Modulatory System Using Cuff Pressure Algometry: Back Translation From Man to Rat
Cummins T, Kucharczyk, MW, Bannister K.
European Journal of Pain, 2020, PMID: 32350984

The impact of bone cancer on the peripheral encoding of mechanical pressure stimuli Kucharczyk, MW*, Chisholm KI, Denk F, Dickenson AH, Bannister K, McMahon SB. Pain, 2020 (preprint: BioRxiv), PMID: 32701848

Neuropathy following spinal nerve injury shares features with the irritable nociceptor phenotype: A back-translational study of oxcarbazepine
Patel R, Kucharczyk MW, Montagut-Bordas C, Lockwood S, Dickenson AH.
European Journal of Pain, 2019, PMID: 30091265

The reduced level of growth factors in an animal model of depression is accompanied by regulated necrosis in the frontal cortex but not in the hippocampus
Kucharczyk MW*, Kurek A, Pomierny B, Detka J, Papp M, Tota K, Budziszewska B. Psychoneuroendocrinology, 2018, PMID: 29775875

Tuning in C-nociceptors to reveal mechanisms in chronic neuropathic pain
Jonas R, Namer B, Stockinger L, Chisholm K, Schnakenberg M, Landmann G, Kucharczyk MW, Konrad C, Schmidt R, Carr R, McMahon SB, Schmelz M, Rukwied R.
Annals of Neurology, 2018, PMID: 29659054

Hypothalamic insulin and glucagon-like peptide-1 levels in an animal model of depression and their effect on corticotropin-releasing hormone promoter gene activity in a hypothalamic cell line Detka J, Slusarczyk J, Kurek A, Kucharczyk MW, Adamus T, Konieczny P, Kubera M, Basta-Kaim A, Lason W, Budziszewska B. Pharmacological Reports, 2018, PMID: 30831439

The multiplicity of spinal AA-5-HT anti-nociceptive action in a rat model of neuropathic pain
Malek N, Kostrzewa M, Makuch W, Pajak A, Kucharczyk MW, Piscitelli F, Przewlocka B, Di Marzo V, Starowicz K.
Pharmacological Research, 2016, PMID: 27326920

Beneficial impact of intracerebroventricular fractalkine administration on behavioral and biochemical changes induced by prenatal stress in adult rats: Possible role of NLRP3 inflammasome pathway
Slusarczyk J, Trojan E, Wydra K, Glombik K, Chamera K, Kucharczyk MW, Budziszewska B, Kubera M, Lason W, Filip M, Basta-Kaim A. Biochemical Pharmacology, 2016, PMID: 27206338

Pro-apoptotic Action of Corticosterone in Hippocampal Organotypic Cultures
Kurek A, Kucharczyk MW, Detka J, Slusarczyk J, Trojan E, Glombik K, Bojarski B, Ludwikowska A, Lason W, Budziszewska B.
Neurotoxicity Research, 2016, PMID: 27189478

Chronic mild stress influences nerve growth factor through a matrix metalloproteinase-dependent mechanism Kucharczyk MW*, Kurek A, Detka J, Slusarczyk J, Papp M, Tota K, Basta-Kaim A, Kubera M, Lason W, Budziszewska B.
Psychoneuroendocrinology, 2015, PMID: 26771945

Brain glucose metabolism in an animal model of depression
Detka J, Kurek A, Kucharczyk MW, Glombik K, Basta-Kaim A, Kubera M, Lason W, Budziszewska B. Neuroscience, 2015, PMID: 25819664

The importance of TRPV1-sensitisation factors for the development of neuropathic pain Malek N, Pajak A, Kolosowska N, Kucharczyk MW, Starowicz K.
Molecular and Cellular Neuroscience, 2015, PMID: 25662734

Alterations in the anandamide metabolism in the development of neuropathic pain Malek N, Kucharczyk MW, Starowicz K.
BioMed Research International, 2014, PMID: 25276812

Review Manuscripts:

Developments in understanding Diffuse Noxious Inhibitory Controls: Pharmacological evidence from pre-clinical research
Kucharczyk, MW^, Valiente D^, Bannister K.
Journal of Pain Research, 2021, PMID: 33907456

Introducing Descending Control of Nociception: a measure of diffuse noxious inhibitory controls in conscious animals
Bannister K^, Kucharczyk, MW^, Graven-Nielsen T, Porreca F.
Pain, 2021, PMID: 33470750

Hopes for the Future of Pain Control Bannister K, Kucharczyk MW, Dickenson. AH. Pain Therapy, 2017, PMID: 28536900