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Dr Julia Gerasimenko
Uwch Ddarlithydd
- Ar gael fel goruchwyliwr ôl-raddedig
Ysgol y Biowyddorau
Trosolwyg
Trosolwg Ymchwil
- Ymchwilio i gyfranogiad sylweddau patholegol gan gynnwys bile, alcohol a metabolau alcohol nad ydynt yn ocsideiddiol wrth gychwyn pancreatitis acíwt.
- Signalau calsiwm ffisiolegol mewn celloedd acinar pancreatig gan gynnwys gweithredoedd ffosffad dinucleotide asid nicotinig (NAADP) a'i rôl mewn ffisioleg a phatholeg y pancreas exocrine.
- Datblygu ceisiadau microsgopeg dau ffoton ar gyfer astudiaethau o pancreas exocrine.
- Atal atalyddion sianel calsiwm sy'n cael eu gweithredu gan ryddhau (CRAC) fel therapi posibl ar gyfer pancreatitis acíwt.
Cyhoeddiad
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)
Ymchwil
Mae fy mhrif ddiddordeb ymchwil yn cael ei gyfeirio ond nid yn gyfyngedig i astudio mecanweithiau ac achosion pancreatitis acíwt. Mae 80% o achosion o pancreatitis acíwt yn gysylltiedig â naill ai reflux bustl neu gam-drin alcohol. Mae effeithiau gwenwynig alcohol yn cael eu cyfryngu'n bennaf gan esters ethyl asid brasterog (FAEE), sy'n cael eu cynhyrchu yn y pancreas pan fo lefelau ocsigen yn yr organ yn isel. Mae FAEEs yn cymell cynnydd gormodol yn y crynodiad ïon calsiwm y tu mewn i gelloedd acinar pancreatig, sydd yn ei dro yn arwain at actifadu ensymau treulio cynamserol. Un o'r ymatebion dilysnod pancreatitis acíwt yw activation cynamserol, mewngellol trypsinogen a'i drosi o zymogen i trypsin gweithredol. Y prif ganlyniad yw marwolaeth celloedd necrotig enfawr a llid y pancreas.
Mae cynllun fy ymchwil yn seiliedig ar ddau ganlyniad allweddol diweddar:
- Mae cenhadau mewnol Ffisiolegol Ca2 + rhyddhau Ca2 + nid yn unig o'r reticulum endoplasmig, ond hefyd o byllau asid yn ardal granule zymogen.
- Mae asidau bustl, cyffuriau alcohol ac alcohol yn rhyddhau calsiwm o'r reticulum endoplasmig a'r pyllau asid. Byddwn yn ymchwilio i'r mecanweithiau penodol sy'n sail i ryddhau Ca2 + gwenwynig o'r gwahanol byllau yn ogystal â'r ffurfiad gwactod dilynol a gweithrediad ensym treulio patholegol sy'n achosi'r clefyd. Bydd ymyriadau penodol yn y rhaeadr signalau patholegol yn cael eu profi i baratoi'r ffordd ar gyfer triniaethau rhesymegol yn y pen draw ymchwilio i gyfranogiad alcohol a'i fetabolion wrth sefydlu pancreatitis.
O ganlyniad i gydweithrediad llwyddiannus â labordy Dr. K. Mikoshiba yn Sefydliad Gwyddoniaeth yr Ymennydd RIKEN, Tokyo, Japan, gwelsom fod actifadu proteas pancreatig trwy metaboledd alcohol yn dibynnu'n bennaf ar ryddhau Ca2 + trwy dderbynyddion IP3 siop asid (Gerasimenko J. et al, PNAS, 2009). Ar hyn o bryd nid oes triniaeth ffarmacolegol benodol ar gyfer pancreatitis. Fodd bynnag, erbyn hyn mae ein hymchwil wedi nodi'r proteinau critigol sy'n gyfrifol am y rhyddhau calsiwm gormodol a dyna lle mae'r broblem yn dechrau gyda'r posibilrwydd o chwilio am gyfansoddion cemegol penodol ar gyfer trin pancreatitis acíwt.
Rwy'n ymchwilio i weithred ffosffad adenine dinucleotide asid nicotinig (NAADP), nofel Ca2+ sy'n rhyddhau negesydd a'i rôl wrth sefydlu prosesau patholegol pancreas exocrine. Mae ein canfyddiadau (Gerasimenko J, et al., JCS, 2006) yn dangos bod y pwll Ca2+ sensitif NAADP wedi'i leoli yn y reticulum endoplasmig ac mewn organynnau asidig, sy'n cael eu cynrychioli gan gronynnau ysgrifenyddiaeth, endosomau a lysosomau. Hyd yn hyn roedd llawer o ansicrwydd ar weithred NAADP mewn systemau mamaliaid. Byddwn yn ymchwilio i ryddhau Ca2+ pellach a elicited NAADP o wahanol organynnau mewn celloedd acinar pancreatig permeabilized a diwylliannau celloedd pancreatig gan ddefnyddio technegau trawsyrru a knockouts gan gynnwys dolen a adroddwyd yn ddiweddar i sianeli TPC2. Rwyf hefyd yn datblygu cymwysiadau optegol sy'n cynnwys microsgopeg dau ffoton ar gyfer y tasgau a amlinellir uchod ac yn benodol techneg permeabilization dau ffoton sy'n caniatáu inni astudio siopau Ca2+ mewngellol bach mewn gwahanol organynnau.
A-D. Enghraifft o athreiddedd y gell gan olau cyffro dwy-ffoton dwysedd uchel (735 nm)
A. Dyblwyd cell acinar pancreatig wedi'i llwytho â Fluo-5N AC cyn permeabilization. Mae dot glas yn dangos lleoliad cymhwysiad golau dau ffoton.
B. Mae'r un gell yn dyblu ar ôl treiddio a thrwythiad gyda dextran Coch Texas (3000 MW). Dim ond y gell isaf sydd wedi'i threiddio ac felly mae'n llachar oherwydd trylediad dextran coch Texas i'r cytoplasm.
C. Mae'r un gell yn dyblu ar ôl golchi allan o Texas Red dextran. Nodyn llai fflworoleuedd o Fluo-5N yn y gell permeabilized isaf.
D. Llun golau a drosglwyddir o'r doublet (ar ôl permeabilization) a ddangosir yn A-C.
E. Rydym wedi dangos bod NAADP -fel IP3 a cADPR - yn rhyddhau Ca2 + nid yn unig o'r ER, ond hefyd o gronfa asid, bafilomycin-sensitif yn yr ardal gronynnog ysgrifenyddol pan fydd pwmp ER Ca2 + yn cael ei atal gan thapsigargin (TG). Mae storfa calsiwm yn newid o ardaloedd gronynnog (glas) a basal (coch). (Gerasimenko et al J Cell Sci 2006)
F. Ca2+ cydrannau signalau a Ca2+-cyfryngu rhyngweithiadau yn y polyn ysgrifenyddol apical celloedd acinar pancreatig. Crynodeb o gasgliadau o arbrofion ar gelloedd permeabilized dau ffoton ac o clamp patch astudiaethau recordio presennol cell cyfan (Gerasimenko et al J Cell Sci 2006; Menteyne et al Curr Biol 2006)
Ffynonellau ariannu cyfredol
- Cyngor Ymchwil Meddygol
- Ymddiriedolaeth Wellcome
Cydweithio â labordai eraill
- Yr Athro Alexei Tepikin, Prifysgol Lerpwl, UK
- Yr Athro Steven Pandol, Prifysgol California, Los Angeles, UDA
- Yr Athro Anna Gukovskaya, Prifysgol California, Los Angeles, UDA
- Dr. Katsuhiko Mikoshiba, Sefydliad Gwyddoniaeth Ymennydd RIKEN, Tokyo, Japan
Cyfraniadau i lyfrau
- Oleg Gerasimenko a Julia Gerasimenko, permeabilization dau ffoton a mesuriadau calsiwm mewn organelles cellog, Pennod 12 yn DULLIAU MEWN CYFRES BIOLEG MOLECIWLAIDD (Golygydd Cyfres J. Walker) DELWEDDU CELLOEDD BYW (Golygydd cyfrol D.B. Papkovsky).
- O. Gerasimenko a J. Gerasimenko, Mesur calsiwm yn yr amlen niwclear a niwcleoplasm, Pennod 7 mewn signalau Calsiwm, Ail Argraffiad, Gwasg Prifysgol Rhydychen, 2001: A Practical Approach, golygwyd gan A. Tepikin, tt. 125-135
- J. Gerasimenko. Mesur Ca 2 + mewn endosomau celloedd cyfan, pennod 11 wrth fesur calsiwm a chalmodulin y tu mewn a'r tu allan celloedd, llawlyfr labordy Springer, golygwyd gan O.H. Petersen, tt.231-247
Aelodau Staff
Myfyrwyr Ymchwil Ôl-raddedig
- Mr Richard Charlesworth
- Dr Shuang Peng
- Miss Eloise Stapleton
- Mr David Evans
- Mr Aled Coughlan
Addysgu
Cydlynydd Asesu/Dirprwyon Modiwlau: Datblygiadau BI3355 mewn Ffisioleg a Phathoffisioleg
Meysydd goruchwyliaeth
Rwyf ar gael i oruchwylio'r prosiectau canlynol:
1. Ymchwilio i ffisioleg a phatholeg y pancreas exocrine, gan ddefnyddio mewn paratoadau a modelau situ pancreatitis acíwt (Gryshchenko et al 2016, Gryshchenko et al 2018, Gryshchenko et al 2020, Gerasimenko et al 2022).
2. Datblygu triniaethau ar gyfer pancreatitis acíwt. Cyhoeddwyd gwahanol ddulliau yn ddiweddar yn Physiological Reviews (Petersen et al 2021 Rolau calsiwm ac ATP yn ffisioleg a phatholeg y pancreas exocrine) ac mewn Calsiwm Cell (Gerasimenko a Gerasimenko 2023 Rôl signalau Ca2 + ym mhatholeg pancreas exocrine).
3. Rôl SARS-CoV2 mewn pancreatitis acíwt (signalau Gryshchenko et al Calsiwm mewn celloedd imiwnedd pancreatig yn y fan a'r lle. Gerasimenko et al 2022, is-uned protein SARS-CoV-2 S 1 Elicits Ca2+ mewnlifiad - Arwyddion Ca2 + Dibynnol mewn celloedd Stellate Pancreatig a Macrophages Yn Situ).
4. Atalyddion sianel CRAC fel triniaeth bosibl ar gyfer pancreatitis acíwt (Gerasimenko et al 2013 Ca2 + blocâd sianel Ca2+ wedi'i actifadu fel offeryn posibl mewn therapi antipancreatitis; Lewis et al 2024 Cyfuniad o'r atalydd sianel CRAC CM4620 a galactose fel therapi posibl ar gyfer pancreatitis acíwt).
Contact Details
GerasimenkoJV@caerdydd.ac.uk
+44 29208 70865
Adeilad Syr Martin Evans, Rhodfa'r Amgueddfa, Caerdydd, CF10 3AX
+44 29208 70865
Adeilad Syr Martin Evans, Rhodfa'r Amgueddfa, Caerdydd, CF10 3AX