![Julia Gerasimenko](https://profiles-cardiff.imgix.net/attachments/1025?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Dr Julia Gerasimenko
Senior Lecturer
- Available for postgraduate supervision
School of Biosciences
Overview
Research Overview
- Investigation of the involvement of pathological substances including bile, alcohol and non-oxidative alcohol metabolites in the initiation of acute pancreatitis.
- Physiological calcium signalling in pancreatic acinar cells including actions of nicotinic acid adenine dinucleotide phosphate (NAADP) and its role in physiology and pathology of the exocrine pancreas.
- Development of two-photon microscopy applications for studies of exocrine pancreas.
- Inhibition of calcium release-activated (CRAC) channel inhibitors as a potential therapy for acute pancreatitis.
Publication
2024
- Gerasimenko, O. V. and Gerasimenko, J. V. 2024. The role of CFTR in diabetes‐induced pancreatic ductal dysfunction. The Journal of Physiology 602(6), pp. 993-994. (10.1113/jp286338)
- Lewis, S., Evans, D., Tsugorka, T., Peng, S., Stauderman, K., Gerasimenko, O. and Gerasimenko, J. 2024. Combination of the CRAC channel inhibitor CM4620 and galactose as a potential therapy for acute pancreatitis. Function 5(4), article number: zqae017. (10.1093/function/zqae017)
2023
- Famili, D. T. et al. 2023. Pancreatitis in RYR1-related disorders. Neuromuscular Disorders 33(10), pp. 769-775. (10.1016/j.nmd.2023.09.003)
- Gerasimenko, J. V. and Gerasimenko, O. V. 2023. The role of Ca2+ signalling in the pathology of exocrine pancreas. Cell Calcium 112, article number: 102740. (10.1016/j.ceca.2023.102740)
- Gerasimenko, J. V. and Gerasimenko, O. V. 2023. Ca 2+ signaling and ATP production in pancreatic cancer. Function 5(1), article number: zqad067. (10.1093/function/zqad067)
2022
- Kusiak, A. A. et al. 2022. Activation of pancreatic stellate cells attenuates intracellular Ca 2+ signals due to downregulation of TRPA1 and protects against cell death induced by alcohol metabolites. Cell Death and Disease 13(8), article number: 744. (10.1038/s41419-022-05186-w)
- Gerasimenko, O. V. and Gerasimenko, J. V. 2022. CRAC channel inhibitors in pancreatic pathologies. Journal of Physiology 600(7), pp. 1597-1598. (10.1113/JP282826)
- Gerasimenko, J. V., Petersen, O. H. and Gerasimenko, O. V. 2022. SARS-CoV-2 S Protein Subunit 1 Elicits Ca2+ Influx – Dependent Ca2+ Signals in Pancreatic Stellate Cells and Macrophages In Situ. Function 3(2) (10.1093/function/zqac002)
2021
- Petersen, O. H., Gerasimenko, J., Gerasimenko, O. V., Gryshchenko, O. and Peng, S. 2021. The roles of calcium and ATP in the physiology and pathology of the exocrine pancreas. Physiological Reviews 101(4), pp. 1691-1744. (10.1152/physrev.00003.2021)
2020
- Gryshchenko, O., Gerasimenko, J., Petersen, O. H. and Gerasimenko, O. V. 2020. Calcium signaling in pancreatic immune cells in situ. Function 2(1), article number: zqaa026. (10.1093/function/zqaa026)
- Petersen, O. H., Gerasimenko, O. V. and Gerasimenko, J. V. 2020. Endocytic uptake of SARS-CoV-2: the critical roles of pH, Ca2+ and NAADP. Function 1(1), article number: zqaa003. (10.1093/function/zqaa003)
2019
- Jakubowska, M. A. et al. 2019. ABT‐199 (Venetoclax), a BH3‐mimetic Bcl‐2 inhibitor, does not cause Ca2+‐signalling dysregulation or toxicity in pancreatic acinar cells. British Journal of Pharmacology 176(22), pp. 4402-4415. (10.1111/bph.14505)
2018
- Peng, S., Gerasimenko, J. V., Tsugorka, T. M., Gryshchenko, O., Samarasinghe, S., Petersen, O. H. and Gerasimenko, O. V. 2018. Galactose protects against cell damage in mouse models of acute pancreatitis. Journal of Clinical Investigation 128(9), pp. 3769-3778. (10.1172/JCI94714)
- Gryshchenko, O., Gerasimenko, J., Peng, S., Gerasimenko, O. V. and Petersen, O. H. 2018. Calcium signalling in the acinar environment of the exocrine pancreas: physiology and pathophysiology. Journal of Physiology 596(14), pp. 2663-2678. (10.1113/JP275395)
- Vervliet, T., Gerasimenko, J. V., Ferdek, P. E., Jakubowska, M. A., Petersen, O. H., Gerasimenko, O. V. and Bultynck, G. 2018. BH4 domain peptides derived from Bcl-2/Bcl-XL as novel tools against acute pancreatitis. Cell Death Discovery 4, article number: 58. (10.1038/s41420-018-0054-5)
- Gerasimenko, J. V., Peng, S., Tsugorka, T. and Gerasimenko, O. V. 2018. Ca 2+ signalling underlying pancreatitis. Cell Calcium 70, pp. 95-101. (10.1016/j.ceca.2017.05.010)
2017
- Ferdek, P. E., Jakubowska, M. A., Polina, N., Gerasimenko, J. V., Gerasimenko, O. V. and Petersen, O. H. 2017. BH3 mimetic-elicited Ca2+ signals in pancreatic acinar cells are dependent on Bax and can be reduced by Ca2+-like peptides. Cell Death and Disease 8, article number: e2640. (10.1038/cddis.2017.41)
2016
- Ferdek, P. E., Jakubowska, M. A., Gerasimenko, J. V., Gerasimenko, O. V. and Petersen, O. H. 2016. Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium-driven bile uptake. Journal of Physiology 594(21), pp. 6147-6164. (10.1113/JP272774)
- Peng, S., Gerasimenko, J. V., Tsugorka, T., Gryshchenko, O., Samarasinghe, S., Petersen, O. H. and Gerasimenko, O. V. 2016. Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 371(1700), article number: 20150423. (10.1098/rstb.2015.0423)
- Jakubowska, M. A., Ferdek, P. E., Gerasimenko, O. V., Gerasimenko, J. V. and Petersen, O. H. 2016. Nitric oxide signals are interlinked with calcium signals in normal pancreatic stellate cells upon oxidative stress and inflammation. Open Biology 6(8), article number: 160149. (10.1098/rsob.160149)
- Gryshchenko, O., Gerasimenko, J. V., Gerasimenko, O. V. and Petersen, O. H. 2016. Calcium signalling in pancreatic stellate cells: mechanisms and potential roles. Cell Calcium 59(2-3), pp. 140-144. (10.1016/j.ceca.2016.02.003)
- Gryshchenko, O., Gerasimenko, J. V., Gerasimenko, O. V. and Petersen, O. H. 2016. Ca2+ signals mediated by bradykinin type 2 receptors in normal pancreatic stellate cells can be inhibited by specific Ca2+ channel blockade. Journal of Physiology 594(2), pp. 281-293. (10.1113/JP271468)
2015
- Gerasimenko, J. et al. 2015. Both RyRs and TPCs are required for NAADP-induced intracellular Ca2+ release. Cell Calcium 58(3), pp. 237-245. (10.1016/j.ceca.2015.05.005)
2014
- Gerasimenko, J. V., Peng, S. and Gerasimenko, O. V. 2014. Role of acidic stores in secretory epithelia. Cell Calcium 55(6), pp. 346-354. (10.1016/j.ceca.2014.04.002)
- Gerasimenko, J. V., Petersen, O. H. and Gerasimenko, O. V. 2014. Monitoring of intra-ER free Ca2+. Wiley Interdisciplinary Reviews: Membrane Transport and Signaling 3(3), pp. 63-71. (10.1002/wmts.106)
- Gerasimenko, J. V., Gerasimenko, O. V. and Petersen, O. H. 2014. The role of Ca2+ in the pathophysiology of pancreatitis. The Journal of Physiology 592(2), pp. 269-280. (10.1113/jphysiol.2013.261784)
2013
- Gerasimenko, J. V. et al. 2013. Ca2+ release-activated Ca2+ channel blockade as a potential tool in antipancreatitis therapy. Proceedings of the National Academy of Sciences of the United States of America 110(32), pp. 13186-13191. (10.1073/pnas.1300910110)
2012
- Ferdek, P., Gerasimenko, J. V., Peng, S., Tepikin, A. V., Petersen, O. H. and Gerasimenko, O. V. 2012. A novel role for Bcl-2 in regulation of cellular calcium extrusion. Current Biology 22(13), pp. 1241-1246. (10.1016/j.cub.2012.05.002)
- Gerasimenko, O. V., Petersen, O. H. and Gerasimenko, J. V. 2012. Role of intracellular acid Ca2+ stores in pathological pancreatic protease activation [Editorial]. Expert Review of Gastroenterology & Hepatology 6(2), pp. 129-131. (10.1586/EGH.12.5)
- Petersen, O. H., Gerasimenko, O. V. and Gerasimenko, J. V. 2012. The war within - unraveling the molecular causes of acute pancreatitis - a potentially deadly disease in which the pancreas essentially digests itself - is yielding clues to how it might be treated. The Scientist 26(2), pp. 40-44.
- Gerasimenko, O. V. and Gerasimenko, J. V. 2012. Mitochondrial function and malfunction in the pathophysiology of pancreatitis. Pflugers Archiv European Journal of Physiology 464(1), pp. 89-99. (10.1007/s00424-012-1117-8)
2011
- Petersen, O. H., Gerasimenko, O. V., Tepikin, A. and Gerasimenko, J. V. 2011. Aberrant Ca2+ signalling through acidic calcium stores in pancreatic acinar cells. Cell Calcium 50(2), pp. 193-199. (10.1016/j.ceca.2011.02.010)
- Petersen, O. H., Gerasimenko, O. V. and Gerasimenko, J. V. 2011. Pathobiology of acute pancreatitis: focus on intracellular calcium and calmodulin. F1000 Medicine Reports(3), article number: 15. (10.3410/M3-15)
- Gerasimenko, J. V. et al. 2011. Calmodulin protects against alcohol-induced pancreatic trypsinogen activation elicited via Ca2+ release through IP3 receptors. Proceedings of the National Academy of Sciences of the United States of America 108(14), pp. 5873-5878. (10.1073/pnas.1016534108)
2010
- Gerasimenko, J. V., Ferdek, P., Fischer, L., Gukovskaya, A. and Pandol, S. 2010. Inhibitors of Bcl-2 protein family deplete ER Ca2+ stores in pancreatic acinar cells. Pflugers Archiv-European Journal of Physiology 460(5), pp. 891-900. (10.1007/s00424-010-0859-4)
- Gerasimenko, O. V. and Gerasimenko, J. V. 2010. Two-photon permeabilization and calcium measurements in cellular organelles. In: Live Cell Imaging: Methods and Protocols., Vol. 591. Methods in Molecular Biology Vol. 2. Springer, pp. 201-210., (10.1007/978-1-60761-404-3_12)
2009
- Baumgartner, H. K. et al. 2009. Calcium elevation in mitochondria is the main Ca2+ requirement for mitochondrial permeability transition pore (mPTP) opening. Journal of Biological Chemistry 284(31), pp. 20796-20803. (10.1074/jbc.M109.025353)
- Petersen, O. H., Tepikin, A. V., Gerasimenko, J. V., Gerasimenko, O. V., Sutton, R. and Criddle, D. N. 2009. Fatty acids, alcohol and fatty acid ethyl esters: Toxic Ca2+ signal generation and pancreatitis. Cell Calcium 45(6), pp. 634-642. (10.1016/j.ceca.2009.02.005)
- Gerasimenko, J. V. et al. 2009. Pancreatic protease activation by alcohol metabolite depends on Ca2+ release via acid store IP3 receptors. Proceedings of the National Academy of Sciences of the United States of America 106(26), pp. 10758-10763. (10.1073/pnas.0904818106)
- Fedirko, N., Gerasimenko, J. V., Tepikin, A. V. and Gerasimenko, O. V. 2009. Regulation of early response genes in pancreatic acinar cells: external calcium and nuclear calcium signalling aspects. Acta Physiologica 195(1), pp. 51-60. (10.1111/j.1748-1716.2008.01935.x)
2008
- Murphy, J. A. et al. 2008. Direct activation of cytosolic Ca2+ signaling and enzyme secretion by cholecystokinin in human pancreatic acinar cells. Gastroenterology 135(2), pp. 632-641. (10.1053/j.gastro.2008.05.026)
2007
- Baumgartner, H. K. et al. 2007. Caspase-8-mediated apoptosis induced by oxidative stress is independent of the intrinsic pathway and dependent on cathepsins. American Journal of Physiology-Gastrointestinal and Liver Physiology 293(1), pp. G296-G307. (10.1152/ajpgi.00103.2007)
- Criddle, D. N. et al. 2007. Calcium signalling and pancreatic cell death: apoptosis or necrosis?. Cell Death and Differentiation 14(7), pp. 1285-1294. (10.1038/sj.cdd.4402150)
2006
- Gerasimenko, J. V., Sherwood, M., Tepikin, A., Petersen, O. H. and Gerasimenko, O. V. 2006. NAADP, cADPR and IP3 all release Ca2+ from the endoplasmic reticulum and an acidic store in the secretory granule area. Journal of Cell Science 119(2), pp. 226-238. (10.1242/jcs.02721)
- Gerasimenko, J. V., Flowerdew, S. E., Voronina, S. G., Sukhomlin, T. K., Tepikin, A. V., Petersen, O. H. and Gerasimenko, O. V. 2006. Bile acids induce Ca2+ release from both the endoplasmic reticulum and acidic intracellular calcium stores through activation of inositol trisphosphate receptors and ryanodine receptors. Journal of Biological Chemistry 281(52), pp. 40154-40163. (10.1074/jbc.M606402200)
2005
- Dolman, N. J., Gerasimenko, J. V., Gerasimenko, O. V., Voronina, S. G., Petersen, O. H. and Tepikin, A. V. 2005. Stable Golgi-mitochondria complexes and formation of Golgi Ca2+ gradients in pancreatic acinar cells. Journal of Biological Chemistry 280(16), pp. 15794-15799. (10.1074/jbc.M412694200)
2004
- Gerasimenko, O. V. and Gerasimenko, J. V. 2004. New aspects of nuclear calcium signalling. Journal of Cell Science 117(15), pp. 3087-3094. (10.1242/jcs.01295)
2003
- Gerasimenko, J. V., Maruyama, Y., Yano, K., Dolman, N. J., Tepikin, A. V., Petersen, O. H. and Gerasimenko, O. V. 2003. NAADP mobilizes Ca2+ from a thapsigargin-sensitive store in the nuclear envelope by activating ryanodine receptors. Journal of Cell Biology 163(2), pp. 271-282. (10.1083/jcb.200306134)
- Gerasimenko, O. V., Maruyama, Y., Tepikin, A., Petersen, O. H. and Gerasimenko, J. V. 2003. Calcium signalling in and around the nuclear envelope. Biochemical Society Transactions 31(1), pp. 76-78.
2002
- Gerasimenko, J. V., Gerasimenko, O. V., Palejwala, A., Tepikin, A., Petersen, O. H. and Watson, A. J. M. 2002. Menadione-induced apoptosis: Roles of cytosolic Ca2+ elevations and the mitochondrial permeability transition pore. Journal of Cell Science 115, pp. 485-497.
- Gerasimenko, O. V., Gerasimenko, J. V., Rizzuto, R. R., Treiman, M., Tepikin, A. V. and Petersen, O. H. 2002. The distribution of the endoplasmic reticulum in living pancreatic acinar cells. Cell Calcium 32(5-6), pp. 261-268. (10.1016/S0143416002001938)
2001
- Gerasimenko, J. V., Gerasimenko, O. V. and Petersen, O. H. 2001. Membrane repair: Ca2+-elicited lysosomal exocytosis. Current Biology 11(23), pp. R971-R974. (10.1016/S0960-9822(01)00577-2)
2000
- Cansela, J. M., Gerasimenko, O. V., Gerasimenko, J. V., Tepikin, A. V. and Petersen, O. H. 2000. Two different but converging messenger pathways to intracellular Ca2+ release: the roles of nicotinic acid adenine dinucleotide phosphate, cyclic ADP-ribose and inositol trisphosphate. Embo Journal 19(11), pp. 2549-2557. (10.1093/emboj/19.11.2549)
Articles
- Gerasimenko, O. V. and Gerasimenko, J. V. 2024. The role of CFTR in diabetes‐induced pancreatic ductal dysfunction. The Journal of Physiology 602(6), pp. 993-994. (10.1113/jp286338)
- Lewis, S., Evans, D., Tsugorka, T., Peng, S., Stauderman, K., Gerasimenko, O. and Gerasimenko, J. 2024. Combination of the CRAC channel inhibitor CM4620 and galactose as a potential therapy for acute pancreatitis. Function 5(4), article number: zqae017. (10.1093/function/zqae017)
- Famili, D. T. et al. 2023. Pancreatitis in RYR1-related disorders. Neuromuscular Disorders 33(10), pp. 769-775. (10.1016/j.nmd.2023.09.003)
- Gerasimenko, J. V. and Gerasimenko, O. V. 2023. The role of Ca2+ signalling in the pathology of exocrine pancreas. Cell Calcium 112, article number: 102740. (10.1016/j.ceca.2023.102740)
- Gerasimenko, J. V. and Gerasimenko, O. V. 2023. Ca 2+ signaling and ATP production in pancreatic cancer. Function 5(1), article number: zqad067. (10.1093/function/zqad067)
- Kusiak, A. A. et al. 2022. Activation of pancreatic stellate cells attenuates intracellular Ca 2+ signals due to downregulation of TRPA1 and protects against cell death induced by alcohol metabolites. Cell Death and Disease 13(8), article number: 744. (10.1038/s41419-022-05186-w)
- Gerasimenko, O. V. and Gerasimenko, J. V. 2022. CRAC channel inhibitors in pancreatic pathologies. Journal of Physiology 600(7), pp. 1597-1598. (10.1113/JP282826)
- Gerasimenko, J. V., Petersen, O. H. and Gerasimenko, O. V. 2022. SARS-CoV-2 S Protein Subunit 1 Elicits Ca2+ Influx – Dependent Ca2+ Signals in Pancreatic Stellate Cells and Macrophages In Situ. Function 3(2) (10.1093/function/zqac002)
- Petersen, O. H., Gerasimenko, J., Gerasimenko, O. V., Gryshchenko, O. and Peng, S. 2021. The roles of calcium and ATP in the physiology and pathology of the exocrine pancreas. Physiological Reviews 101(4), pp. 1691-1744. (10.1152/physrev.00003.2021)
- Gryshchenko, O., Gerasimenko, J., Petersen, O. H. and Gerasimenko, O. V. 2020. Calcium signaling in pancreatic immune cells in situ. Function 2(1), article number: zqaa026. (10.1093/function/zqaa026)
- Petersen, O. H., Gerasimenko, O. V. and Gerasimenko, J. V. 2020. Endocytic uptake of SARS-CoV-2: the critical roles of pH, Ca2+ and NAADP. Function 1(1), article number: zqaa003. (10.1093/function/zqaa003)
- Jakubowska, M. A. et al. 2019. ABT‐199 (Venetoclax), a BH3‐mimetic Bcl‐2 inhibitor, does not cause Ca2+‐signalling dysregulation or toxicity in pancreatic acinar cells. British Journal of Pharmacology 176(22), pp. 4402-4415. (10.1111/bph.14505)
- Peng, S., Gerasimenko, J. V., Tsugorka, T. M., Gryshchenko, O., Samarasinghe, S., Petersen, O. H. and Gerasimenko, O. V. 2018. Galactose protects against cell damage in mouse models of acute pancreatitis. Journal of Clinical Investigation 128(9), pp. 3769-3778. (10.1172/JCI94714)
- Gryshchenko, O., Gerasimenko, J., Peng, S., Gerasimenko, O. V. and Petersen, O. H. 2018. Calcium signalling in the acinar environment of the exocrine pancreas: physiology and pathophysiology. Journal of Physiology 596(14), pp. 2663-2678. (10.1113/JP275395)
- Vervliet, T., Gerasimenko, J. V., Ferdek, P. E., Jakubowska, M. A., Petersen, O. H., Gerasimenko, O. V. and Bultynck, G. 2018. BH4 domain peptides derived from Bcl-2/Bcl-XL as novel tools against acute pancreatitis. Cell Death Discovery 4, article number: 58. (10.1038/s41420-018-0054-5)
- Gerasimenko, J. V., Peng, S., Tsugorka, T. and Gerasimenko, O. V. 2018. Ca 2+ signalling underlying pancreatitis. Cell Calcium 70, pp. 95-101. (10.1016/j.ceca.2017.05.010)
- Ferdek, P. E., Jakubowska, M. A., Polina, N., Gerasimenko, J. V., Gerasimenko, O. V. and Petersen, O. H. 2017. BH3 mimetic-elicited Ca2+ signals in pancreatic acinar cells are dependent on Bax and can be reduced by Ca2+-like peptides. Cell Death and Disease 8, article number: e2640. (10.1038/cddis.2017.41)
- Ferdek, P. E., Jakubowska, M. A., Gerasimenko, J. V., Gerasimenko, O. V. and Petersen, O. H. 2016. Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium-driven bile uptake. Journal of Physiology 594(21), pp. 6147-6164. (10.1113/JP272774)
- Peng, S., Gerasimenko, J. V., Tsugorka, T., Gryshchenko, O., Samarasinghe, S., Petersen, O. H. and Gerasimenko, O. V. 2016. Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 371(1700), article number: 20150423. (10.1098/rstb.2015.0423)
- Jakubowska, M. A., Ferdek, P. E., Gerasimenko, O. V., Gerasimenko, J. V. and Petersen, O. H. 2016. Nitric oxide signals are interlinked with calcium signals in normal pancreatic stellate cells upon oxidative stress and inflammation. Open Biology 6(8), article number: 160149. (10.1098/rsob.160149)
- Gryshchenko, O., Gerasimenko, J. V., Gerasimenko, O. V. and Petersen, O. H. 2016. Calcium signalling in pancreatic stellate cells: mechanisms and potential roles. Cell Calcium 59(2-3), pp. 140-144. (10.1016/j.ceca.2016.02.003)
- Gryshchenko, O., Gerasimenko, J. V., Gerasimenko, O. V. and Petersen, O. H. 2016. Ca2+ signals mediated by bradykinin type 2 receptors in normal pancreatic stellate cells can be inhibited by specific Ca2+ channel blockade. Journal of Physiology 594(2), pp. 281-293. (10.1113/JP271468)
- Gerasimenko, J. et al. 2015. Both RyRs and TPCs are required for NAADP-induced intracellular Ca2+ release. Cell Calcium 58(3), pp. 237-245. (10.1016/j.ceca.2015.05.005)
- Gerasimenko, J. V., Peng, S. and Gerasimenko, O. V. 2014. Role of acidic stores in secretory epithelia. Cell Calcium 55(6), pp. 346-354. (10.1016/j.ceca.2014.04.002)
- Gerasimenko, J. V., Petersen, O. H. and Gerasimenko, O. V. 2014. Monitoring of intra-ER free Ca2+. Wiley Interdisciplinary Reviews: Membrane Transport and Signaling 3(3), pp. 63-71. (10.1002/wmts.106)
- Gerasimenko, J. V., Gerasimenko, O. V. and Petersen, O. H. 2014. The role of Ca2+ in the pathophysiology of pancreatitis. The Journal of Physiology 592(2), pp. 269-280. (10.1113/jphysiol.2013.261784)
- Gerasimenko, J. V. et al. 2013. Ca2+ release-activated Ca2+ channel blockade as a potential tool in antipancreatitis therapy. Proceedings of the National Academy of Sciences of the United States of America 110(32), pp. 13186-13191. (10.1073/pnas.1300910110)
- Ferdek, P., Gerasimenko, J. V., Peng, S., Tepikin, A. V., Petersen, O. H. and Gerasimenko, O. V. 2012. A novel role for Bcl-2 in regulation of cellular calcium extrusion. Current Biology 22(13), pp. 1241-1246. (10.1016/j.cub.2012.05.002)
- Gerasimenko, O. V., Petersen, O. H. and Gerasimenko, J. V. 2012. Role of intracellular acid Ca2+ stores in pathological pancreatic protease activation [Editorial]. Expert Review of Gastroenterology & Hepatology 6(2), pp. 129-131. (10.1586/EGH.12.5)
- Petersen, O. H., Gerasimenko, O. V. and Gerasimenko, J. V. 2012. The war within - unraveling the molecular causes of acute pancreatitis - a potentially deadly disease in which the pancreas essentially digests itself - is yielding clues to how it might be treated. The Scientist 26(2), pp. 40-44.
- Gerasimenko, O. V. and Gerasimenko, J. V. 2012. Mitochondrial function and malfunction in the pathophysiology of pancreatitis. Pflugers Archiv European Journal of Physiology 464(1), pp. 89-99. (10.1007/s00424-012-1117-8)
- Petersen, O. H., Gerasimenko, O. V., Tepikin, A. and Gerasimenko, J. V. 2011. Aberrant Ca2+ signalling through acidic calcium stores in pancreatic acinar cells. Cell Calcium 50(2), pp. 193-199. (10.1016/j.ceca.2011.02.010)
- Petersen, O. H., Gerasimenko, O. V. and Gerasimenko, J. V. 2011. Pathobiology of acute pancreatitis: focus on intracellular calcium and calmodulin. F1000 Medicine Reports(3), article number: 15. (10.3410/M3-15)
- Gerasimenko, J. V. et al. 2011. Calmodulin protects against alcohol-induced pancreatic trypsinogen activation elicited via Ca2+ release through IP3 receptors. Proceedings of the National Academy of Sciences of the United States of America 108(14), pp. 5873-5878. (10.1073/pnas.1016534108)
- Gerasimenko, J. V., Ferdek, P., Fischer, L., Gukovskaya, A. and Pandol, S. 2010. Inhibitors of Bcl-2 protein family deplete ER Ca2+ stores in pancreatic acinar cells. Pflugers Archiv-European Journal of Physiology 460(5), pp. 891-900. (10.1007/s00424-010-0859-4)
- Baumgartner, H. K. et al. 2009. Calcium elevation in mitochondria is the main Ca2+ requirement for mitochondrial permeability transition pore (mPTP) opening. Journal of Biological Chemistry 284(31), pp. 20796-20803. (10.1074/jbc.M109.025353)
- Petersen, O. H., Tepikin, A. V., Gerasimenko, J. V., Gerasimenko, O. V., Sutton, R. and Criddle, D. N. 2009. Fatty acids, alcohol and fatty acid ethyl esters: Toxic Ca2+ signal generation and pancreatitis. Cell Calcium 45(6), pp. 634-642. (10.1016/j.ceca.2009.02.005)
- Gerasimenko, J. V. et al. 2009. Pancreatic protease activation by alcohol metabolite depends on Ca2+ release via acid store IP3 receptors. Proceedings of the National Academy of Sciences of the United States of America 106(26), pp. 10758-10763. (10.1073/pnas.0904818106)
- Fedirko, N., Gerasimenko, J. V., Tepikin, A. V. and Gerasimenko, O. V. 2009. Regulation of early response genes in pancreatic acinar cells: external calcium and nuclear calcium signalling aspects. Acta Physiologica 195(1), pp. 51-60. (10.1111/j.1748-1716.2008.01935.x)
- Murphy, J. A. et al. 2008. Direct activation of cytosolic Ca2+ signaling and enzyme secretion by cholecystokinin in human pancreatic acinar cells. Gastroenterology 135(2), pp. 632-641. (10.1053/j.gastro.2008.05.026)
- Baumgartner, H. K. et al. 2007. Caspase-8-mediated apoptosis induced by oxidative stress is independent of the intrinsic pathway and dependent on cathepsins. American Journal of Physiology-Gastrointestinal and Liver Physiology 293(1), pp. G296-G307. (10.1152/ajpgi.00103.2007)
- Criddle, D. N. et al. 2007. Calcium signalling and pancreatic cell death: apoptosis or necrosis?. Cell Death and Differentiation 14(7), pp. 1285-1294. (10.1038/sj.cdd.4402150)
- Gerasimenko, J. V., Sherwood, M., Tepikin, A., Petersen, O. H. and Gerasimenko, O. V. 2006. NAADP, cADPR and IP3 all release Ca2+ from the endoplasmic reticulum and an acidic store in the secretory granule area. Journal of Cell Science 119(2), pp. 226-238. (10.1242/jcs.02721)
- Gerasimenko, J. V., Flowerdew, S. E., Voronina, S. G., Sukhomlin, T. K., Tepikin, A. V., Petersen, O. H. and Gerasimenko, O. V. 2006. Bile acids induce Ca2+ release from both the endoplasmic reticulum and acidic intracellular calcium stores through activation of inositol trisphosphate receptors and ryanodine receptors. Journal of Biological Chemistry 281(52), pp. 40154-40163. (10.1074/jbc.M606402200)
- Dolman, N. J., Gerasimenko, J. V., Gerasimenko, O. V., Voronina, S. G., Petersen, O. H. and Tepikin, A. V. 2005. Stable Golgi-mitochondria complexes and formation of Golgi Ca2+ gradients in pancreatic acinar cells. Journal of Biological Chemistry 280(16), pp. 15794-15799. (10.1074/jbc.M412694200)
- Gerasimenko, O. V. and Gerasimenko, J. V. 2004. New aspects of nuclear calcium signalling. Journal of Cell Science 117(15), pp. 3087-3094. (10.1242/jcs.01295)
- Gerasimenko, J. V., Maruyama, Y., Yano, K., Dolman, N. J., Tepikin, A. V., Petersen, O. H. and Gerasimenko, O. V. 2003. NAADP mobilizes Ca2+ from a thapsigargin-sensitive store in the nuclear envelope by activating ryanodine receptors. Journal of Cell Biology 163(2), pp. 271-282. (10.1083/jcb.200306134)
- Gerasimenko, O. V., Maruyama, Y., Tepikin, A., Petersen, O. H. and Gerasimenko, J. V. 2003. Calcium signalling in and around the nuclear envelope. Biochemical Society Transactions 31(1), pp. 76-78.
- Gerasimenko, J. V., Gerasimenko, O. V., Palejwala, A., Tepikin, A., Petersen, O. H. and Watson, A. J. M. 2002. Menadione-induced apoptosis: Roles of cytosolic Ca2+ elevations and the mitochondrial permeability transition pore. Journal of Cell Science 115, pp. 485-497.
- Gerasimenko, O. V., Gerasimenko, J. V., Rizzuto, R. R., Treiman, M., Tepikin, A. V. and Petersen, O. H. 2002. The distribution of the endoplasmic reticulum in living pancreatic acinar cells. Cell Calcium 32(5-6), pp. 261-268. (10.1016/S0143416002001938)
- Gerasimenko, J. V., Gerasimenko, O. V. and Petersen, O. H. 2001. Membrane repair: Ca2+-elicited lysosomal exocytosis. Current Biology 11(23), pp. R971-R974. (10.1016/S0960-9822(01)00577-2)
- Cansela, J. M., Gerasimenko, O. V., Gerasimenko, J. V., Tepikin, A. V. and Petersen, O. H. 2000. Two different but converging messenger pathways to intracellular Ca2+ release: the roles of nicotinic acid adenine dinucleotide phosphate, cyclic ADP-ribose and inositol trisphosphate. Embo Journal 19(11), pp. 2549-2557. (10.1093/emboj/19.11.2549)
Book sections
- Gerasimenko, O. V. and Gerasimenko, J. V. 2010. Two-photon permeabilization and calcium measurements in cellular organelles. In: Live Cell Imaging: Methods and Protocols., Vol. 591. Methods in Molecular Biology Vol. 2. Springer, pp. 201-210., (10.1007/978-1-60761-404-3_12)
Research
My primary research interest is directed but not limited to study of mechanisms and causes of acute pancreatitis. 80% cases of acute pancreatitis are associated with either bile reflux or alcohol abuse. The toxic effects of alcohol are principally mediated by fatty acid ethyl esters (FAEE), which are produced in the pancreas when oxygen levels in the organ are low. FAEEs induce an excessive increase in the calcium ion concentration inside pancreatic acinar cells, which in turn leads to premature activation of digestive enzymes. One of the hallmark responses of acute pancreatitis is a premature, intracellular activation of trypsinogen and its conversion from zymogen to active trypsin. The main result is massive necrotic cell death and inflammation of the pancreas.
The plan of my research is based on two recent key findings:
- Physiological Ca2+-liberating internal messengers release Ca2+ not only from the endoplasmic reticulum, but also from acid pools in the zymogen granule area.
- Bile acids, alcohol and alcohol metabolites release calcium from the endoplasmic reticulum and the acid pools. We shall investigate the specific mechanisms underlying toxic Ca2+ release from the various pools as well as the subsequent vacuole formation and pathological digestive enzyme activation that causes the disease. Specific interventions in the pathological signalling cascade will be tested to pave the way for eventual rational treatments investigation of the involvement of alcohol and its metabolites in the induction of pancreatitis.
As the result of successful collaboration with Dr. K. Mikoshiba's laboratory in RIKEN Brain Science Institute, Tokyo, Japan, we found that pancreatic protease activation by alcohol metabolite mainly depends on Ca2+ release via acid store IP3 receptors (Gerasimenko J. et al, PNAS, 2009). Currently there is no specific pharmacological treatment for pancreatitis. However, now our research has identified the critical proteins responsible for the excessive calcium release which is where the problem begins with the possibility to search for specific chemical compounds for the treatment of acute pancreatitis.
I am investigating the action of nicotinic acid adenine dinucleotide phosphate (NAADP), a novel Ca2+ releasing messenger and its role in the induction of pathological processes of exocrine pancreas. Our findings (Gerasimenko J, et al., JCS, 2006) show that the NAADP-sensitive Ca2+ pool is located in the endoplasmic reticulum and in acidic organelles, which are represented by secretory granules, endosomes and lysosomes. So far there was much uncertainty on the action of NAADP in mammalian systems. We shall investigate further NAADP-elicited Ca2+ release from different organelles in permeabilized pancreatic acinar cells and pancreatic cell cultures using transfection and knockouts techniques including recently reported link to TPC2 channels. I am also developing optical applications involving two-photon microscopy for the tasks outlined above and in particular two-photon permeabilization technique that allow us to study small intracellular Ca2+ stores in different organelles.
A-D. Example of permeabilization of the cell by high intensity two-photon excitation light (735 nm)
A. A pancreatic acinar cell doublet loaded with Fluo-5N AM before permeabilization. Blue dot shows the position of two-photon light application.
B. Same cell doublet after permeabilization and perfusion with Texas Red dextran (3000 MW). Only the lower cell has been permeabilized and is therefore bright due to diffusion of Texas Red dextran into the cytoplasm.
C. Same cell doublet after washing out of Texas Red dextran. Note reduced fluorescence of Fluo-5N in the lower permeabilized cell.
D. Transmitted light picture of the doublet (after permeabilization) shown in A-C.
E. We have demonstrated that NAADP –like IP3 and cADPR – releases Ca2+ not only from the ER, but also from an acid, bafilomycin-sensitive pool in the secretory granule area when ER Ca2+ pump is inhibited by thapsigargin (TG). Calcium store changes from granular (blue) and basal (red) areas. (Gerasimenko et al J Cell Sci 2006)
F. Ca2+ signalling components and Ca2+-mediated interactions in the apical secretory pole of pancreatic acinar cells. Summary of conclusions from experiments on two-photon permeabilized cells and from patch clamp whole cell current recording studies (Gerasimenko et al J Cell Sci 2006; Menteyne et al Curr Biol 2006)
Current Sources of funding
- Medical Research Council
- Wellcome Trust
Collaboration with other labs
- Prof. Alexei Tepikin, Liverpool University, UK
- Prof. Steven Pandol, University of California, Los Angeles, USA
- Prof. Anna Gukovskaya, University of California, Los Angeles, USA
- Dr. Katsuhiko Mikoshiba, RIKEN Brain Science Institute, Tokyo, Japan
Contributions to books
- Oleg Gerasimenko and Julia Gerasimenko, Two-photon permeabilization and calcium measurements in cellular organelles, Chapter 12 in METHODS IN MOLECULAR BIOLOGY SERIES (Series Editor J. Walker) LIVE CELL IMAGING (Volume Editor D.B. Papkovsky).
- O. Gerasimenko and J. Gerasimenko, Measuring calcium in the nuclear envelope and nucleoplasm, Chapter 7 in Calcium signalling, Second Edition, Oxford University Press, 2001: A Practical Approach, Edited by A. Tepikin, pp. 125-135
- J. Gerasimenko. Measuring Ca 2+ in Endosomes of Intact Cells, Chapter 11 in Measuring Calcium and Calmodulin Inside and Outside Cells, Springer Lab Manual, Edited by O.H. Petersen, pp.231-247
Staff Members
Postgraduate Research Students
- Mr Richard Charlesworth
- Dr Shuang Peng
- Miss Eloise Stapleton
- Mr David Evans
- Mr Aled Coughlan
Teaching
Assessment Co-ordinator/Module Deputy: BI3355 Advances in Physiology and Pathophysiology
Supervisions
I am available to supervise the following projects:
1. Investigation of physiology and pathology of the exocrine pancreas, using in situ preparations and models of acute pancreatitis (Gryshchenko et al 2016, Gryshchenko et al 2018, Gryshchenko et al 2020, Gerasimenko et al 2022).
2. Development of treatments for acute pancreatitis. Different approaches have been recently published in Physiological Reviews (Petersen et al 2021 The roles of calcium and ATP in the physiology and pathology of the exocrine pancreas) and in Cell Calcium (Gerasimenko&Gerasimenko 2023 The role of Ca2+ signalling in the pathology of exocrine pancreas).
3. Role of SARS-CoV2 in acute pancreatitis (Gryshchenko et al Calcium signaling in pancreatic immune cells in situ. Gerasimenko et al 2022, SARS-CoV-2 S Protein Subunit 1 Elicits Ca2+ Influx – Dependent Ca2+ Signals in Pancreatic Stellate Cells and Macrophages In Situ).
4. CRAC channel inhibitors as a potential treatment for acute pancreatitis (Gerasimenko et al 2013 Ca2+ release-activated Ca2+ channel blockade as a potential tool in antipancreatitis therapy; Lewis et al 2024 Combination of the CRAC channel inhibitor CM4620 and galactose as a potential therapy for acute pancreatitis).
Contact Details
GerasimenkoJV@cardiff.ac.uk
+44 29208 70865
Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX
+44 29208 70865
Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX