Dr Karen Keeshan

  • Reader (Paul O'Gorman Leukaemia Research Centre)

telephone: 0141 3017895
email: Karen.Keeshan@glasgow.ac.uk

R324 Level 3, Paul O'Gorman Leukaemia Res Cent, Gartnavel General Hospital, Glasgow G12 0YN, G12 0xb

ORCID iDhttps://orcid.org/0000-0001-7266-0890

Biography

Dr Karen Keeshan is a Reader in Leukaemia Research at the Paul O’Gorman Leukaemia Research Centre, in the Institute of Cancer Sciences, University of Glasgow. 

Dr Keeshan graduated with a B.Sc. in Biochemistry from the University College Cork, Ireland in 1998. She trained for a PhD degree under the joint supervision of Prof. Tom Cotter and Dr Sharon McKenna and graduated with a PhD on Apoptosis and Chronic Myeloid Leukaemia from University College Cork in 2002.  

Dr Keeshan carried out her postdoctoral training in the USA. She first undertook a post-doctoral research post in Prof. Bruno Calabretta’s laboratory in the Kimmel Cancer Centre, at Thomas Jefferson University, Philadelphia, working on signalling in Chronic Myeloid Leukaemia. She then undertook a second post-doctoral position in Prof. Warren Pear’s laboratory at the University of Pennsylvania. She held two Leukaemia and Lymphoma Society awards, The Leukemia and Lymphoma Society, Special Fellowship Award and The Leukemia and Lymphoma Society, Career Development Award working on Acute Lymphoid and Acute Myeloid leukaemia where she first identified TRIB2 as a novel oncogene.   

In 2008, Dr Keeshan was awarded a President of Ireland Young Researcher award (PIYRA) a highly prestigious award granted by the President of Ireland on behalf of the Irish Government Agency Science Foundation Ireland which supports “future leaders”She also received a Marie Sklodowska-Curie Actions –Individual FellowshipThese enabled Dr Keeshan to establish her Leukaemia research group at the University College Cork, Ireland.  

In 2012, Dr Keeshan moved her research group to the University of Glasgow having been awarded a non clinical Senior Lecturer post in Paediatric Haematology funded by the Howat Foundation and Children with Cancer UK, to develop paediatric leukaemia research in Scotland. She has received additional funding from Blood Cancer UK, Yorkhill Leukaemia & Cancer Research Fund and a number of additional charity, studentship and grant awards. Dr Keeshan reviews for high impact journals, a large number of funding agencies including charities and government, is a panel evaluator for fellowships including Marie Sklodowska-Curie Actions and enjoys collaborating with colleagues across the world, giving seminars and talks at international conferences and institutes. Dr Keeshan is a leader in Tribbles and cancer research, and has co-organised international conferences in this field.  

Dr Keeshan was promoted to Reader in Leukaemia Research in 2016 at the University of GlasgowShe works closely with clinical colleagues at the Royal Hospital for Children and has trained clinical and non-clinical researchers in Leukaemia Research aiming to translate our scientific advances in paediatric leukaemia into clinical practice. Research in the lab focuses on acute myeloid leukaemia and identifying paediatric disease specifications that may improve current therapy. PhD students and post-doctoral researchers in Dr Keeshan’s group are offered opportunities to attend local, national and international conferences and have been awarded prices for selected talks and travel awards. Lab alumni have gone into a variety of careers including academic research, teaching, industry and clinical posts. 

Publications

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Number of items: 67.

2021

Latif, A.-L. et al. (2021) BRD4-mediated repression of p53 is a target for combination therapy in AML. Nature Communications, 12(1), 241. (doi: 10.1038/s41467-020-20378-8) (PMID:33431824) (PMCID:PMC7801601)

Aung, M. M. K., Mills, M. L., Bittencourt-Silvestre, J. and Keeshan, K. (2021) Insights into the molecular profiles of adult and paediatric acute myeloid leukaemia. Molecular Oncology, (doi: 10.1002/1878-0261.12899) (PMID:33421304) (Early Online Publication)

Keeshan, K. (2021) Superenhancing AML with Trib1. Blood, 137(1), pp. 8-9. (doi: 10.1182/blood.2020008315) (PMID:33410899)

Marensi, V., Keeshan, K. R. and MacEwan, D. J. (2021) Pharmacological impact of FLT3 mutations on receptor activity and responsiveness to tyrosine kinase inhibitors. Biochemical Pharmacology, 183, 114348. (doi: 10.1016/j.bcp.2020.114348) (PMID:33242449)

2020

Richmond, L. and Keeshan, K. (2020) Pseudokinases: a tribble‐edged sword. FEBS Journal, 287(19), pp. 4170-4182. (doi: 10.1111/febs.15096) (PMID:31621188)

Mitxitorena, I., Somma, D., Mitchell, J. P., Lepistö, M., Tyrchan, C., Smith, E. L., Kiely, P. A., Walden, H. , Keeshan, K. and Carmody, R. J. (2020) The deubiquitinase USP7 uses a distinct ubiquitin-like domain to deubiquitinate NF-ĸB subunits. Journal of Biological Chemistry, 295(33), pp. 11754-11763. (doi: 10.1074/jbc.RA120.014113) (PMID:32587091) (PMCID:PMC7450122)

Sarrou, E. , Richmond, L., Carmody, R. J. , Gibson, B. and Keeshan, K. (2020) CRISPR gene editing of murine blood stem and progenitor cells induces MLL-AF9 chromosomal translocation and MLL-AF9 leukaemogenesis. International Journal of Molecular Sciences, 21(12), 4266. (doi: 10.3390/ijms21124266) (PMID:32549410) (PMCID:PMC7352880)

2019

Collins, P. E., Somma, D., Kerrigan, D., Herrington, F., Keeshan, K. R. , Nibbs, R. J.B. and Carmody, R. J. (2019) The IκB-protein BCL-3 controls toll-like receptor-induced MAPK activity by promoting TPL-2 degradation in the nucleus. Proceedings of the National Academy of Sciences of the United States of America, 116(51), pp. 25828-25838. (doi: 10.1073/pnas.1900408116) (PMID:31772019) (PMCID:PMC6926074)

Smith, E. L., Somma, D., Kerrigan, D., McIntyre, Z., Cole, J. J., Liang, K. L., Kiely, P. A., Keeshan, K. and Carmody, R. J. (2019) The regulation of sequence specific NF-ĸB DNA binding and transcription by IKKβ Phosphorylation of NF-ĸB p50 at Serine 80. Nucleic Acids Research, 47(21), pp. 11151-11161. (doi: 10.1093/nar/gkz873) (PMID:31598684) (PMCID:PMC6868378)

Mussai, F. et al. (2019) Targeting the arginine metabolic brake enhances immunotherapy for leukaemia. International Journal of Cancer, 145(8), pp. 2201-2208. (doi: 10.1002/ijc.32028) (PMID:30485425) (PMCID:PMC6767531)

2018

Chaudhury, S. et al. (2018) Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias. Nature Communications, 9, 5280. (doi: 10.1038/s41467-018-07584-1) (PMID:30538250) (PMCID:PMC6290074)

Salomé, M. , Hopcroft, L. and Keeshan, K. (2018) Inverse and correlative relationships between TRIBBLES genes indicate non-redundant functions during normal and malignant hemopoiesis. Experimental Hematology, 66, 63-78.e13. (doi: 10.1016/j.exphem.2018.07.005) (PMID:30031847)

Foulkes, D. M. et al. (2018) Covalent inhibitors of EGFR family protein kinases induce degradation of human Tribbles 2 (TRIB2) pseudokinase in cancer cells. Science Signaling, 11(549), eaat7951. (doi: 10.1126/scisignal.aat7951) (PMID:30254057) (PMCID:PMC6553640)

Newcombe, A. A., Gibson, B. E.S. and Keeshan, K. (2018) Harnessing the potential of epigenetic therapies for childhood acute myeloid leukemia. Experimental Hematology, 63, pp. 1-11. (doi: 10.1016/j.exphem.2018.03.008) (PMID:29608923)

Salomé, M. , Magee, A., Yalla, K., Chaudhury, S. , Sarrou, E. , Carmody, R. J. and Keeshan, K. (2018) A Trib2-p38 axis controls myeloid leukaemia cell cycle and stress response signalling. Cell Death and Disease, 9(5), 443. (doi: 10.1038/s41419-018-0467-3) (PMID:29670085) (PMCID:PMC5906628)

O'Connor, C., Yalla, K., Salome, M. , Moka, H. A., Gómez Castañeda, E., Eyers, P. A. and Keeshan, K. (2018) Trib2 expression in granulocyte-monocyte progenitors drives a highly drug resistant acute myeloid leukaemia linked to elevated Bcl2. Oncotarget, 9(19), pp. 14977-14992. (doi: 10.18632/oncotarget.24525) (PMID:29599919) (PMCID:PMC5871090)

2017

Laing, A. A., Harrison, C. J., Gibson, B. E.S. and Keeshan, K. (2017) Unlocking the potential of anti-CD33 therapy in adult and childhood acute myeloid leukaemia. Experimental Hematology, 54, pp. 40-50. (doi: 10.1016/j.exphem.2017.06.007) (PMID:28668350)

Sarrou, E. , Gibson, B. and Keeshan, K. (2017) Absence of Mcm6 mimics haemopoietic ageing and has implications for leukaemic transformation. 46th Annual Scientific Meeting of the ISEH - International Society for Experimental Hematology, Frankfurt, Germany, 24-27 Aug 2017. S69. (doi:10.1016/j.exphem.2017.06.134)

Carmody, R. and Keeshan, K. (2017) The Tribble with APL: a new road to therapy. Cancer Cell, 31(5), pp. 612-613. (doi: 10.1016/j.ccell.2017.04.011) (PMID:28486101)

Eyers, P. A., Keeshan, K. and Kannan, N. (2017) Tribbles in the 21st Century: the evolving roles of Tribbles pseudokinases in biology and disease. Trends in Cell Biology, 27(4), pp. 284-298. (doi: 10.1016/j.tcb.2016.11.002) (PMID:27908682) (PMCID:PMC5382568)

Ahmed, A., Wan, X., Mitxitorena, I., Lindsay, A. J., Pandolfi, P. P., McCaffrey, M. W., Keeshan, K. , Chen, Y. H. and Carmody, R. J. (2017) Regulation of NF-κB by PML and PML-RARα. Scientific Reports, 7, 44539. (doi: 10.1038/srep44539) (PMID:28317833) (PMCID:PMC5357907)

2016

Chaudhury, S. S. , Wheadon, H. , Gibson, B. and Keeshan, K. (2016) The Bone Marrow Niche Distinguishes Young and Old Leukemia. 58th ASH Annual Meeting, San Diego, CA, USA, 3-6 Dec 2016.

O'Connor, C. et al. (2016) The presence of C/EBPα and its degradation are both required for TRIB2 mediated leukaemia. Oncogene, 35(40), pp. 5272-5281. (doi: 10.1038/onc.2016.66) (PMID:26996668)

Keeshan, K. , Vieugué, P., Chaudhury, S. , Rishi, L., Gaillard, C., LIang, L., Garcia, E., Nakumura, T., Omidvar, N. and Kogan, S. C. (2016) Co-operative leukaemogenesis in acute myeloid leukaemia and acute promyelocytic leukaemia reveal C/EBPα as a common target of TRIB1 and PML/RARA. Haematologica, 101(10), pp. 1228-1236. (doi: 10.3324/haematol.2015.138503) (PMID:27390356) (PMCID:PMC5046652)

Liang, K. L., Paredes, R., Carmody, R. , Eyers, P. A., Meyer, S., McCarthy, T. V. and Keeshan, K. (2016) Human TRIB2 oscillates during the cell cycle and promotes ubiquitination and degradation of CDC25C. International Journal of Molecular Sciences, 17(9), 1378. (doi: 10.3390/ijms17091378) (PMID:27563873) (PMCID:PMC5037658)

Chaudhury, S. , Gibson, B. and Keeshan, K. (2016) The Impact of Cellular Age on Leukaemic Transformation. 21st Congress Of The European Hematology Association, Copenhagen, Denmark, 9-12 June 2016. p. 12.

Salomè, M. and Keeshan, K. (2016) TRIB2 Regulates the Cell Cycle Under Stress Conditions in a Murine Cell Model of Leukaemia. 21st Congress Of The European Hematology Association, Copenhagen, Denmark, 9-12 June 2016.

Sarrou, S., Gibson, B. and Keeshan, K. (2016) Efficient Genome Editing of Mouse Hematopoietic Cells Using Crispr/Cas9 Technology. 21st Congress Of The European Hematology Association, Copenhagen, Denmark, 9-12 June 2013. p. 295.

Yalla, K., O'Connor, C., Campos, J. and Keeshan, K. (2016) TRIB2 Transformed GMP is the Myeloid Leukaemia Initiating Cell. 21st Congress Of The European Hematology Association, Copenhagen, Denmark, 9-12 June 2016.

Liang, K. L., O'Connor, C., Veiga, J. P., McCarthy, T. V. and Keeshan, K. (2016) TRIB2 regulates normal and stress-induced thymocyte proliferation. Cell Discovery, 2, 15050. (doi: 10.1038/celldisc.2015.50) (PMID:27462446) (PMCID:PMC4860960)

2015

Latif, A.-L., Cole, J. J., Monteiro Campos, J., Clark, W., McGarry, L., Brock, C., Newcombe, A., Keeshan, K. , Copland, M. and Adams, P. D. (2015) Dual inhibition of MDM2 and BET cooperate to eradicate acute myeloid leukemia. Blood, 126(23), p. 674. (doi: 10.1182/blood.V126.23.674.674)

Salome, M. , Campos, J. and Keeshan, K. (2015) TRIB2 and the ubiquitin proteasome system in cancer. Biochemical Society Transactions, 43(5), pp. 1089-1094. (doi: 10.1042/bst20150103) (PMID:26517929)

Chaudhury, S. S. , Morison, J. K., Gibson, B. E.S. and Keeshan, K. (2015) Insights into cell ontogeny, age and acute myeloid leukaemia. Experimental Hematology, 43(9), pp. 745-755. (doi: 10.1016/j.exphem.2015.05.008) (PMID:26051919)

Liang, K. L., O'Connor, C., McCarthy, T. V. and Keeshan, K. (2015) Investigation of the role of TRIB2 in normal murine hematopoiesis. Experimental Hematology, 43(9), S77. (doi: 10.1016/j.exphem.2015.06.181)

Pellicano, F., O'Connor, C. and Keeshan, K. (2015) An investigation of the leukaemia initiating cell in TRIB2 mediated AML. Experimental Hematology, 43(9), S88. (doi: 10.1016/j.exphem.2015.06.228)

O'Connor, C., Campos, J., Osinski, J. M., Gronostajski, R. M., Michie, A. and Keeshan, K. (2015) Nfix expression critically modulates early B lymphopoiesis and myelopoiesis. PLoS ONE, 10(3), e0120102. (doi: 10.1371/journal.pone.0120102) (PMID:25780920) (PMCID:PMC4363787)

2014

Lohan, F., O'Connor, C., Campos, J., Ohlsson, E., Salome, M. , Forde, C., Cahill, M., Kiely, P., Porse, B. and Keeshan, K. (2014) Targeting C/EBPalpha p42 and oncogene cooperativity in acute myeloid leukaemia. Experimental Hematology, 42(8), S42. (doi: 10.1016/j.exphem.2014.07.153)

O'Connor, C., Campos, J., Murphy, B., Hannon, M., Gronostajski, R., Michie, A. and Keeshan, K. (2014) NFIX influences stem and progenitor lineage fate. Experimental Hematology, 42(8), S54. (doi: 10.1016/j.exphem.2014.07.205)

Ni Ealaithe, C., Rishi, L. and Keeshan, K. (2014) Analysis of Trib genes in leukaemia. Irish Journal of Medical Science, 183(S4), S133-S134. (doi: 10.1007/s11845-014-1153-9)

Rishi, L. et al. (2014) Regulation of Trib2 by an E2F1-C/EBP feedback loop in AML cell proliferation. Blood, 123(15), pp. 2389-2400. (doi: 10.1182/blood-2013-07-511683) (PMID:24516045)

Walsh, S., Gavin, A., Wyatt, S., O'Connor, C., Keeshan, K. , Nolan, Y. M., O'Keeffe, G. W. and Sullivan, A. M. (2014) Knockdown of interleukin-1 receptor 1 is not neuroprotective in the 6-hydroxydopamine striatal lesion rat model of Parkinson's disease. International Journal of Neuroscience, 125(1), pp. 70-77. (doi: 10.3109/00207454.2014.904304)

2013

Lohan, F. et al. (2013) Elucidation and therapeutic targeting of the molecular mechanism of TRIB2-mediated acute myeloid leukaemia. Blood, 122(21), p. 3792.

Ryan, S.M., O’Keeffe, G.W., O'Connor, C., Keeshan, K. and Nolan, Y.M. (2013) Negative regulation of TLX by IL-1β correlates with an inhibition of adult hippocampal neural precursor cell proliferation. Brain, Behavior, and Immunity, 33, pp. 7-13. (doi: 10.1016/j.bbi.2013.03.005)

Keeshan, K. , Hannon, M., Rishi, L., Hasemann, M., Frank, A.-K., Timoney, J., O'Connor, C., Cahill, M. and Porse, B. (2013) E2F1 positively regulates Trib2 pseudokinase expression and proliferation in acute leukaemia. Experimental Hematology, 41(8), S50. (doi: 10.1016/j.exphem.2013.05.197)

Keeshan, K. , O'Connor, C., Campos, J., Murphy, B., Hannon, M. and Michie, A. (2013) NFIX expression critically modulates early B lymphopoiesis and myelopoiesis. Experimental Hematology, 41(8), S68. (doi: 10.1016/j.exphem.2013.05.267)

Liang, K.L., Rishi, L. and Keeshan, K. (2013) Tribbles in acute leukemia. Blood, 121(21), pp. 4265-4270. (doi: 10.1182/blood-2012-12-471300)

Lohan, F. and Keeshan, K. (2013) The functionally diverse roles of tribbles. Biochemical Society Transactions, 41(4), pp. 1096-1100. (doi: 10.1042/BST20130105)

2012

Hannon, M., Lohan, F., Erbilgin, Y., Sayitoglu, M., O’Hagan, K., Mills, K., Ozbek, U. and Keeshan, K. (2012) Elevated TRIB2 with NOTCH1 activation in paediatric/adult T-ALL. British Journal of Haematology, 158(5), pp. 626-634. (doi: 10.1111/j.1365-2141.2012.09222.x)

Lohan, F. M. and Keeshan, K. (2012) Mechanism of Trib2 mediated degradation of C/EBP-ain acute myelogenous leukaemia. British Journal of Haematology, 157(S1), p. 57. (doi: 10.1111/j.1365-2141.2012.09071.x)

Keeshan, K. (2012) Elevated Trib2 with Notch1 activation in pediatric/adult T-ALL. In: British Society for Haematology 52nd Annual Scientific Meeting, Glasgow, 16-18 April 2012,

2011

Hannon, M., Al-Shahrour, F., Ebert, B. L. and Keeshan, K. (2011) Regulation of Trib2 gene expression in normal and AML cells. British Journal of Haematology, 153(Supl 1), pp. 6-7. (doi: 10.1111/j.1365-2141.2011.08609.x)

The Trustees of the University Of Pennsylvania (2011) Diagnostic and Therapeutic Utility of Tribbles-2 in Human Cancers. .

2010

Keeshan, K. (2010) 643 Degradation of C/EBPalpha by Trib proteins correlates with Trib mediated acute myeloid leukemia. European Journal of Cancer Supplements, 8(5), pp. 162-163. (doi: 10.1016/S1359-6349(10)71443-9)

Dedhia, P.H., Keeshan, K. , Uljon, S., Xu, L., Vega, M.E., Shestova, O., Zaks-Zilberman, M., Romany, C., Blacklow, S.C. and Pear, W.S. (2010) Differential ability of Tribbles family members to promote degradation of C/EBP and induce acute myelogenous leukemia. Blood, 116(8), pp. 1321-1328. (doi: 10.1182/blood-2009-07-229450)

Keeshan, K. , Bailis, W., Dedhia, P. H., Vega, M. E., Shestova, O., Xu, L., Toscano, K., Uljon, S. N., Blacklow, S. C. and Pear, W. S. (2010) Transformation by Tribbles homolog 2 (Trib2) requires both the Trib2 kinase domain and COP1 binding. Blood, 116(23), pp. 4948-4957. (doi: 10.1182/blood-2009-10-247361)

2008

Keeshan, K. , Shestova, O., Ussin, L. and Pear, W.S. (2008) Tribbles homolog 2 (Trib2) and HoxA9 cooperate to accelerate acute myelogenous leukemia. Blood Cells, Molecules, and Diseases, 40(1), pp. 119-121. (doi: 10.1016/j.bcmd.2007.06.005)

2007

Wouters, B.J. et al. (2007) Distinct gene expression profiles of acute myeloid/T-lymphoid leukemia with silenced CEBPA and mutations in NOTCH1. Blood, 110(10), pp. 3706-3714. (doi: 10.1182/blood-2007-02-073486)

2006

Chen, Y.-X., Yan, J., Keeshan, K. , Tubbs, A.T., Wang, H., Silva, A., Brown, E.J., Hess, J.L., Pear, W.S. and Hua, X. (2006) The tumor suppressor menin regulates hematopoiesis and myeloid transformation by influencing Hox gene expression. Proceedings of the National Academy of Sciences of the United States of America, 103(4), pp. 1018-1023. (doi: 10.1073/pnas.0510347103)

Ferrari-Amorotti, G., Keeshan, K. , Zattoni, M., Guerzoni, C., Iotti, G., Cattelani, S., Donato, N.J. and Calabretta, B. (2006) Leukemogenesis induced by wild-type and STI571-resistant BCR/ABL is potently suppressed by C/EBP. Blood, 108(4), pp. 1353-1362. (doi: 10.1182/blood-2006-01-011833)

Keeshan, K. et al. (2006) Tribbles homolog 2 inactivates C/EBPα and causes acute myelogenous leukemia. Cancer Cell, 10(5), pp. 401-411. (doi: 10.1016/j.ccr.2006.09.012)

Keeshan, K. et al. (2006) Tribbles homolog 2 (Trib2) inactivates C/EBPalpha and causes acute myelogenous leukemia. Blood, 108(11), p. 776.

Maillard, I., Tu, L., Sambandam, A., Yashiro-Ohtani, Y., Millholland, J., Keeshan, K. , Shestova, O., Xu, L., Bhandoola, A. and Pear, W. S. (2006) The requirement for Notch signaling at the -selection checkpoint in vivo is absolute and independent of the pre-T cell receptor. Journal of Experimental Medicine, 203(10), pp. 2239-2245. (doi: 10.1084/jem.20061020)

2003

Keeshan, K. (2003) Transcription activation function of C/EBP is required for induction of granulocytic differentiation. Blood, 102(4), pp. 1267-1275. (doi: 10.1182/blood-2003-02-0477)

Keeshan, K. , Cotter, T.G. and McKenna, S.L. (2003) Bcr-Abl upregulates cytosolic p21WAF-1/CIP-1by a phosphoinositide-3-kinase (PI3K)-independent pathway. British Journal of Haematology, 123(1), pp. 34-44. (doi: 10.1046/j.1365-2141.2003.04538.x)

2002

Keeshan, K. , Cotter, T.G. and McKenna, S.L. (2002) High Bcr-Abl expression prevents the translocation of Bax and Bad to the mitochondrion. Leukemia, 16(9), pp. 1725-34.

2001

Keeshan, K. , Mills, K.I., Cotter, T.G. and McKenna, S.L. (2001) Elevated Bcr-Abl expression levels are sufficient for a haematopoietic cell line to acquire a drug-resistant phenotype. Leukemia, 15(12), pp. 1823-1833.

2000

Di Bacco, A., Keeshan, K. , McKenna, S. L. and Cotter, T. G. (2000) Molecular abnormalities in chronic myeloid leukemia: deregulation of cell growth and apoptosis. Oncologist, 5(5), pp. 405-415. (doi: 10.1634/theoncologist.5-5-405) (PMID:11040277)

This list was generated on Sat Jun 19 20:15:19 2021 BST.
Number of items: 67.

Articles

Latif, A.-L. et al. (2021) BRD4-mediated repression of p53 is a target for combination therapy in AML. Nature Communications, 12(1), 241. (doi: 10.1038/s41467-020-20378-8) (PMID:33431824) (PMCID:PMC7801601)

Aung, M. M. K., Mills, M. L., Bittencourt-Silvestre, J. and Keeshan, K. (2021) Insights into the molecular profiles of adult and paediatric acute myeloid leukaemia. Molecular Oncology, (doi: 10.1002/1878-0261.12899) (PMID:33421304) (Early Online Publication)

Keeshan, K. (2021) Superenhancing AML with Trib1. Blood, 137(1), pp. 8-9. (doi: 10.1182/blood.2020008315) (PMID:33410899)

Marensi, V., Keeshan, K. R. and MacEwan, D. J. (2021) Pharmacological impact of FLT3 mutations on receptor activity and responsiveness to tyrosine kinase inhibitors. Biochemical Pharmacology, 183, 114348. (doi: 10.1016/j.bcp.2020.114348) (PMID:33242449)

Richmond, L. and Keeshan, K. (2020) Pseudokinases: a tribble‐edged sword. FEBS Journal, 287(19), pp. 4170-4182. (doi: 10.1111/febs.15096) (PMID:31621188)

Mitxitorena, I., Somma, D., Mitchell, J. P., Lepistö, M., Tyrchan, C., Smith, E. L., Kiely, P. A., Walden, H. , Keeshan, K. and Carmody, R. J. (2020) The deubiquitinase USP7 uses a distinct ubiquitin-like domain to deubiquitinate NF-ĸB subunits. Journal of Biological Chemistry, 295(33), pp. 11754-11763. (doi: 10.1074/jbc.RA120.014113) (PMID:32587091) (PMCID:PMC7450122)

Sarrou, E. , Richmond, L., Carmody, R. J. , Gibson, B. and Keeshan, K. (2020) CRISPR gene editing of murine blood stem and progenitor cells induces MLL-AF9 chromosomal translocation and MLL-AF9 leukaemogenesis. International Journal of Molecular Sciences, 21(12), 4266. (doi: 10.3390/ijms21124266) (PMID:32549410) (PMCID:PMC7352880)

Collins, P. E., Somma, D., Kerrigan, D., Herrington, F., Keeshan, K. R. , Nibbs, R. J.B. and Carmody, R. J. (2019) The IκB-protein BCL-3 controls toll-like receptor-induced MAPK activity by promoting TPL-2 degradation in the nucleus. Proceedings of the National Academy of Sciences of the United States of America, 116(51), pp. 25828-25838. (doi: 10.1073/pnas.1900408116) (PMID:31772019) (PMCID:PMC6926074)

Smith, E. L., Somma, D., Kerrigan, D., McIntyre, Z., Cole, J. J., Liang, K. L., Kiely, P. A., Keeshan, K. and Carmody, R. J. (2019) The regulation of sequence specific NF-ĸB DNA binding and transcription by IKKβ Phosphorylation of NF-ĸB p50 at Serine 80. Nucleic Acids Research, 47(21), pp. 11151-11161. (doi: 10.1093/nar/gkz873) (PMID:31598684) (PMCID:PMC6868378)

Mussai, F. et al. (2019) Targeting the arginine metabolic brake enhances immunotherapy for leukaemia. International Journal of Cancer, 145(8), pp. 2201-2208. (doi: 10.1002/ijc.32028) (PMID:30485425) (PMCID:PMC6767531)

Chaudhury, S. et al. (2018) Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias. Nature Communications, 9, 5280. (doi: 10.1038/s41467-018-07584-1) (PMID:30538250) (PMCID:PMC6290074)

Salomé, M. , Hopcroft, L. and Keeshan, K. (2018) Inverse and correlative relationships between TRIBBLES genes indicate non-redundant functions during normal and malignant hemopoiesis. Experimental Hematology, 66, 63-78.e13. (doi: 10.1016/j.exphem.2018.07.005) (PMID:30031847)

Foulkes, D. M. et al. (2018) Covalent inhibitors of EGFR family protein kinases induce degradation of human Tribbles 2 (TRIB2) pseudokinase in cancer cells. Science Signaling, 11(549), eaat7951. (doi: 10.1126/scisignal.aat7951) (PMID:30254057) (PMCID:PMC6553640)

Newcombe, A. A., Gibson, B. E.S. and Keeshan, K. (2018) Harnessing the potential of epigenetic therapies for childhood acute myeloid leukemia. Experimental Hematology, 63, pp. 1-11. (doi: 10.1016/j.exphem.2018.03.008) (PMID:29608923)

Salomé, M. , Magee, A., Yalla, K., Chaudhury, S. , Sarrou, E. , Carmody, R. J. and Keeshan, K. (2018) A Trib2-p38 axis controls myeloid leukaemia cell cycle and stress response signalling. Cell Death and Disease, 9(5), 443. (doi: 10.1038/s41419-018-0467-3) (PMID:29670085) (PMCID:PMC5906628)

O'Connor, C., Yalla, K., Salome, M. , Moka, H. A., Gómez Castañeda, E., Eyers, P. A. and Keeshan, K. (2018) Trib2 expression in granulocyte-monocyte progenitors drives a highly drug resistant acute myeloid leukaemia linked to elevated Bcl2. Oncotarget, 9(19), pp. 14977-14992. (doi: 10.18632/oncotarget.24525) (PMID:29599919) (PMCID:PMC5871090)

Laing, A. A., Harrison, C. J., Gibson, B. E.S. and Keeshan, K. (2017) Unlocking the potential of anti-CD33 therapy in adult and childhood acute myeloid leukaemia. Experimental Hematology, 54, pp. 40-50. (doi: 10.1016/j.exphem.2017.06.007) (PMID:28668350)

Carmody, R. and Keeshan, K. (2017) The Tribble with APL: a new road to therapy. Cancer Cell, 31(5), pp. 612-613. (doi: 10.1016/j.ccell.2017.04.011) (PMID:28486101)

Eyers, P. A., Keeshan, K. and Kannan, N. (2017) Tribbles in the 21st Century: the evolving roles of Tribbles pseudokinases in biology and disease. Trends in Cell Biology, 27(4), pp. 284-298. (doi: 10.1016/j.tcb.2016.11.002) (PMID:27908682) (PMCID:PMC5382568)

Ahmed, A., Wan, X., Mitxitorena, I., Lindsay, A. J., Pandolfi, P. P., McCaffrey, M. W., Keeshan, K. , Chen, Y. H. and Carmody, R. J. (2017) Regulation of NF-κB by PML and PML-RARα. Scientific Reports, 7, 44539. (doi: 10.1038/srep44539) (PMID:28317833) (PMCID:PMC5357907)

O'Connor, C. et al. (2016) The presence of C/EBPα and its degradation are both required for TRIB2 mediated leukaemia. Oncogene, 35(40), pp. 5272-5281. (doi: 10.1038/onc.2016.66) (PMID:26996668)

Keeshan, K. , Vieugué, P., Chaudhury, S. , Rishi, L., Gaillard, C., LIang, L., Garcia, E., Nakumura, T., Omidvar, N. and Kogan, S. C. (2016) Co-operative leukaemogenesis in acute myeloid leukaemia and acute promyelocytic leukaemia reveal C/EBPα as a common target of TRIB1 and PML/RARA. Haematologica, 101(10), pp. 1228-1236. (doi: 10.3324/haematol.2015.138503) (PMID:27390356) (PMCID:PMC5046652)

Liang, K. L., Paredes, R., Carmody, R. , Eyers, P. A., Meyer, S., McCarthy, T. V. and Keeshan, K. (2016) Human TRIB2 oscillates during the cell cycle and promotes ubiquitination and degradation of CDC25C. International Journal of Molecular Sciences, 17(9), 1378. (doi: 10.3390/ijms17091378) (PMID:27563873) (PMCID:PMC5037658)

Liang, K. L., O'Connor, C., Veiga, J. P., McCarthy, T. V. and Keeshan, K. (2016) TRIB2 regulates normal and stress-induced thymocyte proliferation. Cell Discovery, 2, 15050. (doi: 10.1038/celldisc.2015.50) (PMID:27462446) (PMCID:PMC4860960)

Latif, A.-L., Cole, J. J., Monteiro Campos, J., Clark, W., McGarry, L., Brock, C., Newcombe, A., Keeshan, K. , Copland, M. and Adams, P. D. (2015) Dual inhibition of MDM2 and BET cooperate to eradicate acute myeloid leukemia. Blood, 126(23), p. 674. (doi: 10.1182/blood.V126.23.674.674)

Salome, M. , Campos, J. and Keeshan, K. (2015) TRIB2 and the ubiquitin proteasome system in cancer. Biochemical Society Transactions, 43(5), pp. 1089-1094. (doi: 10.1042/bst20150103) (PMID:26517929)

Chaudhury, S. S. , Morison, J. K., Gibson, B. E.S. and Keeshan, K. (2015) Insights into cell ontogeny, age and acute myeloid leukaemia. Experimental Hematology, 43(9), pp. 745-755. (doi: 10.1016/j.exphem.2015.05.008) (PMID:26051919)

Liang, K. L., O'Connor, C., McCarthy, T. V. and Keeshan, K. (2015) Investigation of the role of TRIB2 in normal murine hematopoiesis. Experimental Hematology, 43(9), S77. (doi: 10.1016/j.exphem.2015.06.181)

Pellicano, F., O'Connor, C. and Keeshan, K. (2015) An investigation of the leukaemia initiating cell in TRIB2 mediated AML. Experimental Hematology, 43(9), S88. (doi: 10.1016/j.exphem.2015.06.228)

O'Connor, C., Campos, J., Osinski, J. M., Gronostajski, R. M., Michie, A. and Keeshan, K. (2015) Nfix expression critically modulates early B lymphopoiesis and myelopoiesis. PLoS ONE, 10(3), e0120102. (doi: 10.1371/journal.pone.0120102) (PMID:25780920) (PMCID:PMC4363787)

Lohan, F., O'Connor, C., Campos, J., Ohlsson, E., Salome, M. , Forde, C., Cahill, M., Kiely, P., Porse, B. and Keeshan, K. (2014) Targeting C/EBPalpha p42 and oncogene cooperativity in acute myeloid leukaemia. Experimental Hematology, 42(8), S42. (doi: 10.1016/j.exphem.2014.07.153)

O'Connor, C., Campos, J., Murphy, B., Hannon, M., Gronostajski, R., Michie, A. and Keeshan, K. (2014) NFIX influences stem and progenitor lineage fate. Experimental Hematology, 42(8), S54. (doi: 10.1016/j.exphem.2014.07.205)

Ni Ealaithe, C., Rishi, L. and Keeshan, K. (2014) Analysis of Trib genes in leukaemia. Irish Journal of Medical Science, 183(S4), S133-S134. (doi: 10.1007/s11845-014-1153-9)

Rishi, L. et al. (2014) Regulation of Trib2 by an E2F1-C/EBP feedback loop in AML cell proliferation. Blood, 123(15), pp. 2389-2400. (doi: 10.1182/blood-2013-07-511683) (PMID:24516045)

Walsh, S., Gavin, A., Wyatt, S., O'Connor, C., Keeshan, K. , Nolan, Y. M., O'Keeffe, G. W. and Sullivan, A. M. (2014) Knockdown of interleukin-1 receptor 1 is not neuroprotective in the 6-hydroxydopamine striatal lesion rat model of Parkinson's disease. International Journal of Neuroscience, 125(1), pp. 70-77. (doi: 10.3109/00207454.2014.904304)

Lohan, F. et al. (2013) Elucidation and therapeutic targeting of the molecular mechanism of TRIB2-mediated acute myeloid leukaemia. Blood, 122(21), p. 3792.

Ryan, S.M., O’Keeffe, G.W., O'Connor, C., Keeshan, K. and Nolan, Y.M. (2013) Negative regulation of TLX by IL-1β correlates with an inhibition of adult hippocampal neural precursor cell proliferation. Brain, Behavior, and Immunity, 33, pp. 7-13. (doi: 10.1016/j.bbi.2013.03.005)

Keeshan, K. , Hannon, M., Rishi, L., Hasemann, M., Frank, A.-K., Timoney, J., O'Connor, C., Cahill, M. and Porse, B. (2013) E2F1 positively regulates Trib2 pseudokinase expression and proliferation in acute leukaemia. Experimental Hematology, 41(8), S50. (doi: 10.1016/j.exphem.2013.05.197)

Keeshan, K. , O'Connor, C., Campos, J., Murphy, B., Hannon, M. and Michie, A. (2013) NFIX expression critically modulates early B lymphopoiesis and myelopoiesis. Experimental Hematology, 41(8), S68. (doi: 10.1016/j.exphem.2013.05.267)

Liang, K.L., Rishi, L. and Keeshan, K. (2013) Tribbles in acute leukemia. Blood, 121(21), pp. 4265-4270. (doi: 10.1182/blood-2012-12-471300)

Lohan, F. and Keeshan, K. (2013) The functionally diverse roles of tribbles. Biochemical Society Transactions, 41(4), pp. 1096-1100. (doi: 10.1042/BST20130105)

Hannon, M., Lohan, F., Erbilgin, Y., Sayitoglu, M., O’Hagan, K., Mills, K., Ozbek, U. and Keeshan, K. (2012) Elevated TRIB2 with NOTCH1 activation in paediatric/adult T-ALL. British Journal of Haematology, 158(5), pp. 626-634. (doi: 10.1111/j.1365-2141.2012.09222.x)

Lohan, F. M. and Keeshan, K. (2012) Mechanism of Trib2 mediated degradation of C/EBP-ain acute myelogenous leukaemia. British Journal of Haematology, 157(S1), p. 57. (doi: 10.1111/j.1365-2141.2012.09071.x)

Hannon, M., Al-Shahrour, F., Ebert, B. L. and Keeshan, K. (2011) Regulation of Trib2 gene expression in normal and AML cells. British Journal of Haematology, 153(Supl 1), pp. 6-7. (doi: 10.1111/j.1365-2141.2011.08609.x)

Keeshan, K. (2010) 643 Degradation of C/EBPalpha by Trib proteins correlates with Trib mediated acute myeloid leukemia. European Journal of Cancer Supplements, 8(5), pp. 162-163. (doi: 10.1016/S1359-6349(10)71443-9)

Dedhia, P.H., Keeshan, K. , Uljon, S., Xu, L., Vega, M.E., Shestova, O., Zaks-Zilberman, M., Romany, C., Blacklow, S.C. and Pear, W.S. (2010) Differential ability of Tribbles family members to promote degradation of C/EBP and induce acute myelogenous leukemia. Blood, 116(8), pp. 1321-1328. (doi: 10.1182/blood-2009-07-229450)

Keeshan, K. , Bailis, W., Dedhia, P. H., Vega, M. E., Shestova, O., Xu, L., Toscano, K., Uljon, S. N., Blacklow, S. C. and Pear, W. S. (2010) Transformation by Tribbles homolog 2 (Trib2) requires both the Trib2 kinase domain and COP1 binding. Blood, 116(23), pp. 4948-4957. (doi: 10.1182/blood-2009-10-247361)

Keeshan, K. , Shestova, O., Ussin, L. and Pear, W.S. (2008) Tribbles homolog 2 (Trib2) and HoxA9 cooperate to accelerate acute myelogenous leukemia. Blood Cells, Molecules, and Diseases, 40(1), pp. 119-121. (doi: 10.1016/j.bcmd.2007.06.005)

Wouters, B.J. et al. (2007) Distinct gene expression profiles of acute myeloid/T-lymphoid leukemia with silenced CEBPA and mutations in NOTCH1. Blood, 110(10), pp. 3706-3714. (doi: 10.1182/blood-2007-02-073486)

Chen, Y.-X., Yan, J., Keeshan, K. , Tubbs, A.T., Wang, H., Silva, A., Brown, E.J., Hess, J.L., Pear, W.S. and Hua, X. (2006) The tumor suppressor menin regulates hematopoiesis and myeloid transformation by influencing Hox gene expression. Proceedings of the National Academy of Sciences of the United States of America, 103(4), pp. 1018-1023. (doi: 10.1073/pnas.0510347103)

Ferrari-Amorotti, G., Keeshan, K. , Zattoni, M., Guerzoni, C., Iotti, G., Cattelani, S., Donato, N.J. and Calabretta, B. (2006) Leukemogenesis induced by wild-type and STI571-resistant BCR/ABL is potently suppressed by C/EBP. Blood, 108(4), pp. 1353-1362. (doi: 10.1182/blood-2006-01-011833)

Keeshan, K. et al. (2006) Tribbles homolog 2 inactivates C/EBPα and causes acute myelogenous leukemia. Cancer Cell, 10(5), pp. 401-411. (doi: 10.1016/j.ccr.2006.09.012)

Keeshan, K. et al. (2006) Tribbles homolog 2 (Trib2) inactivates C/EBPalpha and causes acute myelogenous leukemia. Blood, 108(11), p. 776.

Maillard, I., Tu, L., Sambandam, A., Yashiro-Ohtani, Y., Millholland, J., Keeshan, K. , Shestova, O., Xu, L., Bhandoola, A. and Pear, W. S. (2006) The requirement for Notch signaling at the -selection checkpoint in vivo is absolute and independent of the pre-T cell receptor. Journal of Experimental Medicine, 203(10), pp. 2239-2245. (doi: 10.1084/jem.20061020)

Keeshan, K. (2003) Transcription activation function of C/EBP is required for induction of granulocytic differentiation. Blood, 102(4), pp. 1267-1275. (doi: 10.1182/blood-2003-02-0477)

Keeshan, K. , Cotter, T.G. and McKenna, S.L. (2003) Bcr-Abl upregulates cytosolic p21WAF-1/CIP-1by a phosphoinositide-3-kinase (PI3K)-independent pathway. British Journal of Haematology, 123(1), pp. 34-44. (doi: 10.1046/j.1365-2141.2003.04538.x)

Keeshan, K. , Cotter, T.G. and McKenna, S.L. (2002) High Bcr-Abl expression prevents the translocation of Bax and Bad to the mitochondrion. Leukemia, 16(9), pp. 1725-34.

Keeshan, K. , Mills, K.I., Cotter, T.G. and McKenna, S.L. (2001) Elevated Bcr-Abl expression levels are sufficient for a haematopoietic cell line to acquire a drug-resistant phenotype. Leukemia, 15(12), pp. 1823-1833.

Di Bacco, A., Keeshan, K. , McKenna, S. L. and Cotter, T. G. (2000) Molecular abnormalities in chronic myeloid leukemia: deregulation of cell growth and apoptosis. Oncologist, 5(5), pp. 405-415. (doi: 10.1634/theoncologist.5-5-405) (PMID:11040277)

Conference or Workshop Item

Sarrou, E. , Gibson, B. and Keeshan, K. (2017) Absence of Mcm6 mimics haemopoietic ageing and has implications for leukaemic transformation. 46th Annual Scientific Meeting of the ISEH - International Society for Experimental Hematology, Frankfurt, Germany, 24-27 Aug 2017. S69. (doi:10.1016/j.exphem.2017.06.134)

Chaudhury, S. S. , Wheadon, H. , Gibson, B. and Keeshan, K. (2016) The Bone Marrow Niche Distinguishes Young and Old Leukemia. 58th ASH Annual Meeting, San Diego, CA, USA, 3-6 Dec 2016.

Chaudhury, S. , Gibson, B. and Keeshan, K. (2016) The Impact of Cellular Age on Leukaemic Transformation. 21st Congress Of The European Hematology Association, Copenhagen, Denmark, 9-12 June 2016. p. 12.

Salomè, M. and Keeshan, K. (2016) TRIB2 Regulates the Cell Cycle Under Stress Conditions in a Murine Cell Model of Leukaemia. 21st Congress Of The European Hematology Association, Copenhagen, Denmark, 9-12 June 2016.

Sarrou, S., Gibson, B. and Keeshan, K. (2016) Efficient Genome Editing of Mouse Hematopoietic Cells Using Crispr/Cas9 Technology. 21st Congress Of The European Hematology Association, Copenhagen, Denmark, 9-12 June 2013. p. 295.

Yalla, K., O'Connor, C., Campos, J. and Keeshan, K. (2016) TRIB2 Transformed GMP is the Myeloid Leukaemia Initiating Cell. 21st Congress Of The European Hematology Association, Copenhagen, Denmark, 9-12 June 2016.

Conference Proceedings

Keeshan, K. (2012) Elevated Trib2 with Notch1 activation in pediatric/adult T-ALL. In: British Society for Haematology 52nd Annual Scientific Meeting, Glasgow, 16-18 April 2012,

Patents

The Trustees of the University Of Pennsylvania (2011) Diagnostic and Therapeutic Utility of Tribbles-2 in Human Cancers. .

This list was generated on Sat Jun 19 20:15:19 2021 BST.

Grants

Grants and Awards listed are those received whilst working with the University of Glasgow.

  • The role of the Bone Marrow Microenvironment in Acute Myeloid Leukaemia (AML) Drug Resistance.

    2021 - 2022
     
  • Targeting ERBB signalling in acute myeloid leukaemia

    2019 - 2022
     
  • Investigation of CD33-targeted therapy in childhood acute myeloid leukaemia (AML)

    2016 - 2019
     
  • The influence of the microenvironment in paediatric AML

    2016 - 2018
     
  • Dissecting the function of Bcl-3 in NF-kappaB signaling in B cells

    2015 - 2018
     
  • The importance of stem cell ontogeny in paediatric and adult acute myeloid leukaemia

    2014 - 2016
     
  • Investigating leukaemic stem cell responses following CD33-targeted therapy and the implications for low and high risk paediatric AML groups

    2014 - 2015
     
  • Targeting Trib2 oncogenic signalling in normal and malignant stem cells.

    2013 - 2016
     

Supervision

SUPERVISION

Dr Karen Keeshan supervises Postdoctoral researchers, clinical research fellows and PhD students from countries around the world including Ireland, UK, Greece, Italy, Saudi Arabia, Egypt, Malaysia, Portugal, India, China, Spain, Poland, Australia 

Dr Karen Keeshan supervises Masters students (MSc, MRes and MScifrom different courses and Institutes e.g. Cancer Sciences, Immunology, Biomedical Sciences. 

The lab also hosts students for final year undergraduate projects, Erasmus internships, summer internships, and second level school experiences. 

 

 

Teaching

TEACHING

Dr Karen Keeshan teaches and assesses on a number of masters and medicine courses;  

MB ChB BSc Intercalated course 

MSc Cancer research & Precision Oncology 

MB ChB Haematology and Oncology 

MSc Molecular Pathology 

MSc/MRes Biomedical Sciences 

MRes Biomedical Sciences and Integrative Mammalian biology 

Dr Karen Keeshan is external and internal PhD Thesis examiner for students at Universities across the UK and EU 

 

STEM AMBASSODOR 

D Karen Keeshan is a STEM Ambassador in Scotland Hub. She is available to provide STEM activities to primary school and second level schools in the area.  


External and Social Media Links