Professor Hari Hundal FHEA FRSB
Research
The research programme in the Hundal lab is aimed at defining the intracellular signalling processes that regulate uptake, storage and metabolism of nutrients (e.g. glucose, fatty acids and amino acids) with particular focus on how cells sense nutrient availability and how nutrient over-load can induce metabolic disorders such as insulin resistance and diabetes. More recently, the Hundal lab has also opened up a new and exciting area of study that principally aims to develop our understanding of the action of a class of compounds, termed cannabinoids, in peripheral tissues such as skeletal muscle. Cannabinoids are present in cannabis, but our bodies naturally create cannabinoid-like chemicals, known as endocannabinoids that lock-on to protein molecules found on the surface of cells called cannabinoid receptors (i.e. CB1 and CB2). Pathological over-activation of the endocannabinoid system (ECS) is a feature of obesity and diabetes and one that we have recently discovered to be upregulated during aging and to influence insulin signalling and energy metabolism in skeletal muscle. For more detail and information of our research in the above areas please visit the research page on the Hundal Lab website.
Teaching
I am involved in the delivery and management of taught modules to undergraduate students at Level 3 and Level 4 taking degrees within our Biomedicial Sciences teaching programme.
BS31013 - Biomembranes
BS31019 - Regulatory Physiology and Pharmacology
BS42014 – Diabetes, Obesity and Metabolic Dysfunction
Publications
Stretton, C, Lipina, C, Hyde, R, Cwiklinski, E, Hoffmann, TM, Taylor, PM & Hundal, HS 2019, 'CDK7 is a component of the integrated stress response regulating SNAT2 (SLC38A2)/System A adaptation in response to cellular amino acid deprivation' Biochimica et Biophysica Acta. Molecular Cell Research, vol. 1866, no. 6, pp. 978-991. https://doi.org/10.1016/j.bbamcr.2019.03.002
Lipina, C, Walsh, SK, Mitchell, SE, Speakman, JR, Wainwright, CL & Hundal, H 2019, 'GPR55 deficiency is associated with increased adiposity and impaired insulin signaling in peripheral metabolic tissues' FASEB Journal, vol. 33, no. 1, pp. 1299-1312. https://doi.org/10.1096/fj.201800171R
Nisr, R, Shah, D, Ganley, I & Hundal, H 2019, 'Proinflammatory NFkB signalling promotes mitochondrial dysfunction in skeletal muscle in response to cellular fuel overloading' Cellular and Molecular Life Sciences, pp. 1-18. https://doi.org/10.1007/s00018-019-03148-8
Lu, H, Bogdanovic, E, Yu, Z, Cho, C, Liu, L, Ho, K, Guo, J, Yeung, LSN, Lehmann, R, Hundal, HS, Giacca, A & Fantus, IG 2018, 'Combined Hyperglycemia and Hyperinsulinemia-induced Insulin Resistance in Adipocytes is associated with Dual Signaling Defects mediated by PKC-ζ' Endocrinology, vol. 159, no. 4, pp. 1658-1677. https://doi.org/10.1210/en.2017-00312
Hoffmann, T, Cwiklinski, E, Shah, D, Stretton, C, Hyde, R, Taylor, P & Hundal, H 2018, 'Effects of sodium and amino acid substrate availability upon the expression and stability of the SNAT2 (SLC38A2) amino acid transporter' Frontiers in Pharmacology, vol. 9, 63, pp. 1-9. https://doi.org/10.3389/fphar.2018.00063
Lipina, C & Hundal, HS 2017, 'Lipid modulation of skeletal muscle mass and function' Journal of Cachexia, Sarcopenia and Muscle, vol. 8, no. 2, pp. 190-201. https://doi.org/10.1002/jcsm.12144
Lipina, C & Hundal, HS 2017, 'The endocannabinoid system: no longer anonymous in the control of nitrergic signalling?' Journal of Molecular Cell Biology, vol. 9, no. 2, pp. 91-103. https://doi.org/10.1093/jmcb/mjx008
Lipina, C, Vaanholt, LM, Davidova, A, Mitchell, SE, Storey-Gordon, E, Hambly, C, Irving, AJ, Speakman, JR & Hundal, HSH 2016, 'CB1 receptor blockade counters age-induced insulin resistance and metabolic dysfunction' Aging Cell, vol. 15, no. 2, pp. 325-335. https://doi.org/10.1111/acel.12438
Tilston-Lünel, AM, Haley, KE, Schlecht, NF, Wang, Y, Chatterton, ALD, Moleirinho, S, Watson, A, Hundal, HS, Prystowsky, MB, Gunn-Moore, FJ & Reynolds, PA 2016, 'Crumbs 3b promotes tight junctions in an ezrin-dependent manner in mammalian cells' Journal of Molecular Cell Biology, vol. 8, no. 5, pp. 439-455. https://doi.org/10.1093/jmcb/mjw020
Watson, A, Lipina, C, McArdle, HJ, Taylor, PM & Hundal, H 2016, 'Iron depletion suppresses mTORC1-directed signalling in intestinal Caco-2 cells via induction of REDD' Cellular Signalling, vol. 28, no. 5, pp. 412-424. https://doi.org/10.1016/j.cellsig.2016.01.014
Lipina, C & Hundal, H 2016, 'Is REDD1 a Metabolic Éminence Grise?' Trends in Endocrinology and Metabolism, vol. 27, no. 12, pp. 868-880. https://doi.org/10.1016/j.tem.2016.08.005
Lipina, C & Hundal, HS 2016, 'Modulation of cellular redox homeostasis by the endocannabinoid system' Open Biology, vol. 6, no. 4, 150276, pp. 1-10. https://doi.org/10.1098/rsob.150276
Lipina, C & Hundal, HS 2015, 'Ganglioside GM3 as a gatekeeper of obesity-associated insulin resistance: evidence and mechanisms' FEBS Letters, vol. 589, no. 21, pp. 3221-3227. https://doi.org/10.1016/j.febslet.2015.09.018
Stretton, C, Hoffmann, TM, Munson, MJ, Prescott, A, Taylor, PM, Ganley, IG & Hundal, H 2015, 'GSK3-mediated raptor phosphorylation supports amino acid-dependent Q2 mTORC1-directed signalling' Biochemical Journal, vol. 470, no. 2, pp. 207-221. https://doi.org/10.1042/BJ20150404
Lipina, C, Nardi, F, Grace, H & Hundal, HS 2015, 'NEU3 sialidase as a marker of insulin sensitivity: Regulation by fatty acids' Cellular Signalling, vol. 27, no. 9, pp. 1742-1750. https://doi.org/10.1016/j.cellsig.2015.05.010
Nardi, F, Hoffmann, TM, Stretton, C, Cwiklinski, E, Taylor, PM & Hundal, HS 2015, 'Proteasomal modulation of cellular SNAT2 (SLC38A2) abundance and function by unsaturated fatty acid availability' Journal of Biological Chemistry, vol. 290, no. 13, pp. 8173-8184. https://doi.org/10.1074/jbc.M114.625137
Lipina, C & Hundal, HS 2014, 'Carnosic acid stimulates glucose uptake in skeletal muscle cells via a PME-1/PP2A/PKB signalling axis' Cellular Signalling, vol. 26, no. 11, pp. 2343-2349. https://doi.org/10.1016/j.cellsig.2014.07.022
Mahfouz, R, Khoury, R, Blachnio-Zabielska, A, Turban, S, Loiseau, N, Lipina, C, Stretton, C, Bourron, O, Ferré, P, Foufelle, F, Hundal, HS & Hajduch, E 2014, 'Characterising the inhibitory actions of ceramide upon insulin signaling in different skeletal muscle cell models: a mechanistic insight' PLoS ONE, vol. 9, no. 7, e101865. https://doi.org/10.1371/journal.pone.0101865
Nardi, F, Lipina, C, Magill, D, Hage Hassan, R, Hajduch, E, Gray, A & Hundal, HS 2014, 'Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A' PLoS ONE, vol. 9, no. 3, e92255. https://doi.org/10.1371/journal.pone.0092255
Lipina, C, Irving, AJ & Hundal, HS 2014, 'Mitochondria: a possible nexus for the regulation of energy homeostasis by the endocannabinoid system?' American Journal of Physiology, Endocrinology and Metabolism, vol. 307, no. 1, pp. E1-E13. https://doi.org/10.1152/ajpendo.00100.2014
Macrae, K, Stretton, C, Lipina, C, Blachnio-Zabielska, A, Baranowski, M, Gorski, J, Marley, A & Hundal, HS 2013, 'Defining the role of DAG, mitochondrial function, and lipid deposition in palmitate-induced proinflammatory signaling and its counter-modulation by palmitoleate' Journal of Lipid Research, vol. 54, no. 9, pp. 2366-2378. https://doi.org/10.1194/jlr.M036996
Nardi, F, Lipina, C, Magill, D & Hundal, HS 2013, 'Insulin sensitising effects of monounsaturated and polyunsaturated fatty acids in skeletal muscle cells' Diabetic Medicine, vol. 30, no. Suppl. 1, P70, pp. 49-49. https://doi.org/10.1111/dme.12091_1
Lipina, C, Macrae, K, Suhm, T, Weigert, C, Blachnio-Zabielska, A, Baranowksi, M, Gorski, J, Burgess, K & Hundal, HS 2013, 'Mitochondrial Substrate Availability and its Role in Lipid-Induced Insulin Resistance and Proinflammatory Signalling in Skeletal Muscle' Diabetes, vol. 62, no. 10, pp. 3426-3436. https://doi.org/10.2337/db13-0264
Turban, S, Stretton, C, Drouin, O, Green, CJ, Watson, ML, Gray, A, Ross, F, Lantier, L, Viollet, B, Hardie, DG, Marette, A & Hundal, HS 2012, 'Defining the contribution of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) in regulation of glucose uptake by metformin in skeletal muscle cells' Journal of Biological Chemistry, vol. 287, no. 24, pp. 20088-20099. https://doi.org/10.1074/jbc.M111.330746
Lipina, C, Rastedt, W, Irving, AJ & Hundal, HS 2012, 'New vistas for treatment of obesity and diabetes? Endocannabinoid signalling and metabolism in the modulation of energy balance' BioEssays, vol. 34, no. 8, pp. 681-691. https://doi.org/10.1002/bies.201200031