Cancer Neurophysiology Research Group
The Cancer Neurophysiology Research Group combines neurobiology with oncology. Our goal is to understand the neurogenic regulation of tumorigenesis and tumor-associated pain. Using state-of-the-art techniques (including in vivo optical imaging, electrophysiology, and optogenetics), we selectively monitor and modulate the activity of genetically defined neuronal populations to investigate their influence on tumor biology.
We aim to develop innovative therapies for cancer and cancer-related pain based on a deep understanding of the nervous system.
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Our research also focuses on the presynaptic modulation of sensory endings in the spinal cord, which represents one of the key mechanisms regulating pain perception and immune responses within the tumor. Using advanced electrophysiological approaches and in vivo calcium imaging, we analyze how signals originating from the brain affect the activity of peripheral sensory neurons, and how this influence shapes the tumor microenvironment.
This perspective not only allows us to better understand the neurobiological foundations of cancer pain, but also to identify new therapeutic targets at the intersection of neurobiology and oncology.
Meet our team
Dr. Mateusz W. Kucharczyk
The researcher’s profile is being prepared.
Dr. Joanna Bernacka
Joanna leads the physiological part of the project dedicated to noradrenergic modulation of central sensory terminals.
Dr. Eliza Kramarska
Eliza specializes in silico approaches. Her research interests include host–microbe interactions and the application of advanced computational techniques in biology. She is also actively involved in science communication and science policy, collaborating with initiatives at both the local and European level.
Dr. Ewelina Krzywińska
The researcher’s profile is being prepared.
Dr. Łukasz Pietras
Łukasz works on a bone cancer model, studying the influence of dormant nociceptors on tumor development.
Julia Niemczycka
Julia is primarily responsible for genotyping and overseeing wet lab operations.
Oleksandra Babeshko
The researcher’s profile is being prepared.
Research & findings
The research conducted by the Neurophysiology of Oncology Research Group bridges neurobiology and oncology. Our goal is to understand the neurogenic regulation of tumor development and the associated pain.
Using state-of-the-art techniques (including in vivo optical imaging, electrophysiology, and optogenetics), we selectively monitor and modulate the activity of genetically defined neuronal populations to investigate their influence on tumor biology. We aim to develop innovative cancer therapies and pain treatments based on a deep understanding of the nervous system.
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Neurobiology of cancer
Neuronal pathways running from the brain to the spinal cord influence the perception of somatic stimuli. They regulate the activity of spinal and primary sensory neurons, allowing the brain to precisely adjust the level of signals transmitted through the spinal cord and to exert peripheral control via neurogenic mechanisms.
Importantly, there is continuous dialogue between the nervous system and the tumor. For example, denervation of the tumor can slow down or even halt its growth. Neuropeptides released by peptidergic nociceptors stimulate tumor neovascularization and support immune surveillance of cancer cells. Moreover, early-stage tumors typically do not cause pain.
We believe that presynaptic modulation of sensory endings in the central nervous system is a key element not only for nociception and pain control but also for other aspects of (patho)physiology.
It may represent a neuro-immunological link to the periphery, particularly relevant in the context of neurogenic regulation of tumor- and immunity-related changes in peripheral tissues. Since tumor development is regulated by neurogenic factors, controlling neuronal activity may lead to a new class of anticancer therapies.
Perceptual flexibility, pain, and nociception
The human brain is remarkably powerful and capable of reinterpreting the nature of sensory stimuli. The same stimulus can be perceived as very painful or barely noticeable depending on the circumstances — for example, a wound hurts more at home than on the battlefield (Beecher, 1946). This perceptual flexibility is driven by descending modulatory control — neural circuits influencing the activity of spinal projection neurons that integrate the entirety of ascending somatosensory information.
Nociception can also be modulated through direct effects of descending brain pathways on the central terminals of primary afferents. In this way, the brain can “set the level of pain” transmitted through the spinal cord — the first checkpoint at which nociception can be centrally modulated, making it an attractive target for analgesic therapies. Additionally, the central terminals of primary afferents are influenced by local spinal circuits, which themselves receive descending modulation.
Due to technical challenges, presynaptic control of thinly myelinated afferents (nociceptors) has been poorly studied so far, even though it plays a crucial role in understanding the mechanisms of nociception and neurogenic control of tumors and immune responses. Thanks to new technologies, unprecedented biophysical analyses of these terminals are now possible, opening the door to the development of new pain therapies.
Inside the lab
We combine high-throughput in vivo electrophysiology (e.g., Neuropixels) and calcium imaging (miniscope imaging, two-photon microscopy) with opto- and chemogenetic modulation of genetically and anatomically defined neuronal pathways.
We record the activity of spinal and peripheral neurons and correlate it with animal behavior, using advanced analyses supported by machine learning methods. Our goal is to link the functioning of neuronal networks with the ability to exert top-down control over nociception and tumor processes.
We analyze tumor changes and their microenvironment using state-of-the-art technologies: 3D tumor reconstruction (tissue clearing and light-sheet imaging), flow cytometry (FACS), RNA sequencing (RNA-seq), and high-throughput spectroscopy. Thanks to collaborations with centers worldwide, our approach is also applied clinically — through somatosensory tests, MRI/PET imaging, and computed tomography (CT).
Research projects
Neuro-Immune Cancer Consortium – NICC
Funding:
National Agency for Academic Exchange
Project Manager:
Dr. Mateusz Kucharczyk
Noradrenergic Modulation of the Central Sensory Terminals – Nomod
Funding:
National Science Centre
Project Manager:
Dr. Mateusz Kucharczyk
From research to publication
The importance of TRPV1-sensitisation factors for the development of neuropathic pain
Malek Natalia, Pajak Agnieszka, Kolosowska Natalia [et al.]
Molecular and Cellular Neuroscience, 2015, vol. 65, pp.1-10. DOI:10.1016/j.mcn.2015.02.001
Chronic mild stress influences nerve growth factor through a matrix metalloproteinase-dependent mechanism
Kucharczyk Mateusz, Kurek Anna, Detka Jan [et al.]
Psychoneuroendocrinology, 2016, vol. 66, pp.11-21. DOI:10.1016/j.psyneuen.2015.12.019
Deep sequencing of Phox2a nuclei reveals five classes of anterolateral system neurons
Bell Andrew M., Utting Charlotte, Dickie Allen C. [et al.]
Proceedings of the National Academy of Sciences of the United States of America, 2024, vol. 121, no. 23. DOI:10.1073/pnas.2314213121