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Department of Physiology, Development and Neuroscience

 

Research

Cancer Neuroscience

My lab carries out research in the emerging field of cancer neuroscience: how cancer cells use neural mechanisms, how they interact with the nervous system, and how cancer arises in, or metastasizes to the brain. We focus on how ion channels control membrane potential and intracellular calcium signalling in cancer cells. Cancers such as pancreatic neuroendocrine tumours, small-cell lung cancer and some breast and prostate cancers show neural or neuroendocrine characteristics, including excitability and vesicular release of peptides and neurotransmitters. We want to understand how such signalling participates in the invasiveness and progression of these cancers. As well as these neuroendocrine-differentiated cancers, we are interested in how brain-metastatic cancer cells interact with neurons, and how neurotransmitter signalling at synapses promotes survival, invasion and growth of brain metastases, for example of breast cancer. We use a combination of patch-clamp and optical recording techniques, cell culture and computational modelling.

Collaborators

Leanne Li (Crick Institute)
Douglas Hanahan (EPFL, Lausanne)
Hugo Zeberg (Karolinska Institute, Stockholm)
Ole Paulsen (PDN)
Bill Colledge (PDN)

 

Publications

Key publications: 

 

Recent publications

Zeberg H, Dannemann M, Sahlholm K, Tsuo K, Maricic T, Wiebe V, Hevers W, Robinson HPC, Kelso J, and Pääbo S (2020). A Neanderthal sodium channel increases pain sensitivity in present-day humans. Current Biology, in press, published online: https://doi.org/10.1016/j.cub.2020.06.045. (See also: “Neanderthal gene linked to pain sensitivity” News, Nature 583:665).

Zeng Q, Michael IP, Zhang P, Saghafinia S, Knott G, Jiao W, McCabe BD, Galván, JA, Robinson HPC, Zlobec I, Ciriello G, Hanahan D (2019) Synaptic proximity enables NMDAR signalling to promote brain metastasis. Nature 573:526–531. (See also News and Views: Barria A (2019) Dangerous liaisons as tumour cells form synapses with neurons. Nature 573:499–501).

Li, L., Zeng, Q., Bhutkar, A., Galván, J.A., Karamitopoulou, E., Noordermeer, D., Peng, M.-W., Piersigilli, A., Perren, A., Zlobec, I., Robinson, H., Iruela-Arispe M.L. and Hanahan, D. (2018). GKAP acts as a genetic modulator of NMDAR signaling to govern invasive tumor growth. Cancer Cell 33, 1–16.

Mendonça, P.R.F., Kyle, V., Yeo, S.-H., Colledge, W.H., and Robinson, H.P.C. (2018). Kv4.2 channel activity controls intrinsic firing dynamics of arcuate kisspeptin neurons: Kv4.2 potassium channels and firing irregularity in kisspeptin neurons. J. Physiol. 596, 885–899.

Robinson, H.P.C., and Li, L. (2017). Autocrine, paracrine and necrotic NMDA receptor signalling in mouse pancreatic neuroendocrine tumour cells. Open Biol. 7, 170221.

Scheppach, C., and Robinson, H.P.C. (2017). Fluctuation analysis in nonstationary conditions: single Ca2+ channel current in pyramidal neurons. Biophys. J. 113, 2383–2395.

Butler, J.L., Mendonca, P.R.F., Robinson, H.P.C., and Paulsen, O. (2016). Intrinsic Cornu Ammonis Area 1 theta-nested gamma oscillations induced by optogenetic theta frequency stimulation. J. Neurosci. 36, 4155–4169.

Mendonça, P.R., Vargas-Caballero, M., Erdélyi, F., Szabó, G., Paulsen, O., and Robinson, H.P. (2016). Stochastic and deterministic dynamics of intrinsically irregular firing in cortical inhibitory interneurons. Elife 5, e16475.

Spike generation in the neocortex

Zeberg H, Robinson HPC, Århem P, (2015), Density of voltage-gated potassium channels is a bifurcation parameter in pyramidal neurons, J. Neurophysiol, 113:537-49

Robinson HPC, (2013), Dynamic clamp - synthetic conductances and their influence on membrane potential, Encyclopedia of Biophysics, Springer, pp 527-533

Catterall WA, Raman IM, Robinson HPC, Sejnowski TJ, Paulsen O, (2012), The Hodgkin-Huxley heritage: from channels to circuits, J. Neurosci, 32:14064–14073

Gouwens NW, Zeberg H, Tsumoto K, Tateno T, Aihara K, Robinson HPC, (2010), Synchronization of firing in cortical fast-spiking interneurons at gamma frequencies: a phase-resetting analysis, PLoS Comp Biol, 6: e1000951

Tateno T, Robinson HPC (2009), Integration of broadband conductance input in rat somatosensory cortical inhibitory interneurons: an inhibition-controlled switch between intrinsic and input-driven spiking in fast-spiking cells, J Neurophysiol, 101: 1056-72

Morita K, Kalra R, Aihara K, Robinson HPC, (2008), Recurrent synaptic input and the timing of gamma-frequency-modulated firing of pyramidal cells during neocortical "UP" states, J Neurosci, 28: 1871-81

Electrophysiology of human pluripotent stem-cell (hPSC) derived cortical neurons

Kirwan P, Turner-Bridger B, Peter M, Momoh A, Arambepola D, Robinson HPC, Livesey FJ, (2015), Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro, Development, 142:3178-3187

Shi Y, Kirwan P, Smith J, Robinson HPC, Livesey FJ, (2012), Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses, Nat Neurosci, 15: 477-86, S1

NMDA receptor gating

Kim N-K, Robinson HPC, (2011), Effects of divalent cations on slow unblock of native NMDA receptors in mouse neocortical pyramidal neurons, Eur J Neurosci, 34: 199-212

Vargas-Caballero M, Robinson HPC, (2004), Fast and slow voltage-dependent dynamics of magnesium block in the NMDA receptor: the asymmetric trapping block model, J Neurosci, 24: 6171-80

Computational modelling

Vella M, Cannon RC, Crook S, Davison AP, Ganapathy G, Robinson HPC, Silver RA, Gleeson P, (2014), libNeuroML and PyLEMS: using Python to combine procedural and declarative modeling approaches in computational neuroscience, Front Neuroinform, 8:38

Li X, Morita K, Robinson HPC, Small M, (2013), Control of layer 5 pyramidal cell spiking by oscillatory inhibition in the distal apical dendrites: a computational modeling study, J Neurophysiol, 109:2739-56

Teaching and Supervisions

Teaching: 

Lectures in: 1B Neurobiology; Part 2 PDN, Modules P7 (Pathophysiology of Cancer), N2 (Molecular and Cellular Neuroscience), N7 (Local Circuits and Neural Networks)

University Senior Lecturer
Picture of Dr Hugh  Robinson

Contact Details

+44 (0) 1223 333828 Lab: 333835, Fax: 333840
Email address: