Professor Chris Pepper

Research

For more than two decades, Chris’ research has focused on understanding the mechanisms that underpin the development of disease progression and drug resistance using primary chronic lymphocytic leukaemia (CLL) cells as a model. Chris maintains that the study of this disseminated tumour represents an unrivalled opportunity to unravel these processes as longitudinal sampling from both the lymphoid tissues and the peripheral blood is possible. There is an increasing realisation that tumour pathology and the development of drug resistance are not only determined by the intrinsic tumour genotype but are also influenced by the interplay between tumour cells and the different microenvironments in which they reside. In order to address this, Chris’ team have developed a physiologically relevant, multi-compartment, in vitro models to mimic these tumour microenvironments and investigate the molecular drivers of tumour cell trafficking, homing and tissue retention.

His research is almost entirely patient-focussed; most of his work is based on primary CLL cells and has a strong translational element designed to improve patient care. In this regard, his team were the first to demonstrate the clinical importance of the BCL2 family of proteins and the transcription factor NF-κB in modulating disease progression and response to drugs. His background in medicinal chemistry has led to a strong interest in evaluating the efficacy and mechanisms of action of novel pre-clinical agents. His current drug development programme includes agents targeting IKKα, NIK, CDK9, CXCR4 and ATR.

Selected publications

Slusarczyk, Magdalena, Serpi, Michaela, Ghazaly, Essam, Kariuki, Benson M, McGuigan, Christopher and Pepper, Chris (2021) Single Diastereomers of the Clinical Anticancer ProTide Agents NUC-1031 and NUC-3373 Preferentially Target Cancer Stem Cells In Vitro. Journal of Medicinal Chemistry, 64 (12). pp. 8179-8193. ISSN 0022-2623

Kennedy, Emma, Coulter, Eve Marie, Halliwell, Emma, Profitos-Peleja, Nuria, Walsby, Elisabeth, Clark, Barnaby, Phillips, Elizabeth H, Burley, Thomas A, Mitchell, Simon, Devereux, Stephen, Jones, Christopher Iain, Johnston, Rosalynd, Chevassut, Timothy J, Pepper, Chris, Pepper, Andrea G S and others, (2021) TLR9 expression in Chronic Lymphocytic Leukemia identifies a pro-migratory subpopulation and novel therapeutic target. Blood. pp. 1-32. ISSN 0006-4971 

Lewis, Thomas, Corcoran, David B, Thurston, David E, Giles, Peter J, Ashelford, Kevin, Walsby, Elisabeth J, Fegan, Christopher D, Pepper, Andrea G S, Rahman, Khondaker Miraz and Pepper, Christopher (2020) Novel pyrrolobenzodiazepine benzofused hybrid molecules inhibit NF-κB activity and synergise with bortezomib and ibrutinib in hematological cancers. Haematologica. ISSN 0390-6078

Cohen, Jared A, Rossi, Francesca Maria, Zucchetto, Antonella, Bomben, Riccardo, Terzi-di-Bergamo, Lodovico, Rabe, Kari G, Degan, Massimo, Steffan, Agostino, Polesel, Jerry, Santinelli, Enrico, Innocenti, Idanna, Cutrona, Giovanna, D' Arena, Giovanni, Pozzato, Gabriele, Pepper, Christopher J and others, (2019) A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia. Haematologica, 104. ISSN 0390-6078

Tissino, Erika, Pozzo, Federico, Benedetti, Dania, Caldana, Chiara, Bittolo, Tamara, Rossi, Francesca Maria, Bomben, Riccardo, Nanni, Paola, Chivilò, Hillarj, Cattarossi, Ilaria, Zaina, Eva, Norris, Kevin, Polesel, Jerry, Gentile, Massimo, Pepper, Chris and others, (2020) CD49d promotes disease progression in chronic lymphocytic leukemia: new insights from CD49d bimodal expression. Blood, 135 (15). pp. 1244-1254. ISSN 0006-4971

Norris, Kevin, Hillmen, Peter, Rawstron, Andrew, Hills, Robert, Baird, Duncan M, Fegan, Christopher D and Pepper, Chris (2019) Telomere length predicts for outcome to FCR chemotherapy in CLL. Leukemia. ISSN 0887-6924

Twohig, Jason P, Cardus Figueras, Ana, Andrews, Robert, Wiede, Florian, Cossins, Benjamin C, Derrac Soria, Alicia, Lewis, Myles J, Townsend, Michael J, Millrine, David, Li, Jasmine, Hill, David G, Uceda Fernandez, Javier, Liu, Xiao, Szomolay, Barbara, Pepper, Christopher J, Taylor, Philip R, Pitzalis, Costantino, Tiganis, Tony, Williams, Nigel M, Jones, Gareth W and Jones, Simon A (2019) Activation of naïve CD4+ T cells re-tunes STAT1 signaling to deliver unique cytokine responses in memory CD4+ T cells. Nature Immunology, 20. pp. 458-470. ISSN 1529-2908

Pepper, Andrea G S, Zucchetto, Antonella, Norris, Kevin, Tissino, Erika, Polesel, Jerry, Soe, Zarni, Allsup, David, Hockaday, Anna, Ow, Pei Loo, Hillmen, Peter, Rawstron, Andrew, Catovsky, Daniel, Bulian, Pietro, Bomben, Riccardo, Baird, Duncan M, Fegan, Christopher D, Gattei, Valter and Pepper, Chris (2021) Combined analysis of IGHV mutations, telomere length and CD49d identifies long-term progression-free survivors in TP53 wild-type CLL treated with FCR-based therapies. Leukemia. pp. 1-4. ISSN 0887-6924 

Hyatt S, Jones RE, Heppel NH, Grimstead JW, et al. Telomere length is a critical determinant for survival in multiple myeloma. Br J Haematol. 2017 Mar 24. doi:10.1111/bjh.14643. [Epub ahead of print] PubMed PMID: 28342200.

Law PJ, Berndt SI, Speedy HE, Camp NJ, et al. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia. Nat Commun. 2017 Feb 6;8:14175. doi:10.1038/ncomms14175. PubMed PMID: 28165464; PubMed Central PMCID: PMC5303820.

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