Dr Paolo Gallipoli
Position: CRUK Advanced Clinician Scientist Fellow/Honorary Consultant Haematologist
Personal home page: http://www.haem.cam.ac.uk/staff/senior-staff/dr-brian-huntly/group-members/dr-paolo-gallipoli/
PubMed journal articles - click here
My research interests focus on mechanisms of disease initiation and maintenance and the identification and validation of novel therapeutic targets in myeloid leukaemia. Sequencing and mechanistic studies have improved our understanding of the biology of several subtypes of myeloid leukaemias. This has in turn resulted in the development of more targeted and scientifically validated therapies. However, the overall treatment outcomes, even with the introduction of novel agents, remain suboptimal for most patients, mainly as a result of disease relapse. Both chronic and acute myeloid leukaemia arises in a haematopoietic stem or progenitor cell, which has the ability to self-renew, following the acquisition of recurrent driver mutations. This cell of origin, usually named the Leukaemia Stem Cell (LSC), represents the reservoir for relapse due to its inherent or acquired resistance to current therapies. Therefore, an improved understanding of the molecular mechanisms causing disease relapse, particularly at the LSC level, is required to improve patient outcome.
My research studies the role of adaptive responses to current therapies, including novel targeted therapies, in several subtypes of myeloid leukaemias and at LSC level, with a specific focus on the role of metabolic adaptations, as a mechanism of resistance not driven by genetic mutations. Using a combination of forward genetic screening and cell barcoding, functional characterisation and mechanistic studies, I aim to characterise the clonal dynamics in leukaemic cell populations under therapeutic stress, characterise the mechanisms leading to therapy resistance and identify novel therapeutic vulnerabilities to be targeted in combination with standard therapies in these conditions.
I am also interested in the role that the bidirectional cross-talk between altered metabolism and aberrant signalling and transcriptional programmes play in the establishment of myeloid leukaemias. I am specifically studying how metabolic intermediates interact with transcriptional programmes in acute myeloid leukaemia and conversely how specific driver mutations impact on cellular metabolism to enable leukaemic transformation.
Symplectic Elements feed provided by Research Information, University of Cambridge
1) Gallipoli P, Giotopoulos G, Tzelepis K, Costa ASH, Vohra S, Medina-Perez P, Basheer F, Marando L, Di Lisio L, Dias JML, Yun H, Sasca D, Horton SJ, Vassiliou G, Frezza C & Huntly BJP (2018)
Glutaminolysis is a metabolic dependency in FLT3ITD acute myeloid leukemia unmasked by FLT3 tyrosine kinase inhibition. Blood 131, 1639-1653 – Plenary Paper – corresponding author
2) Gallipoli P & Huntly BJP (2017)
Novel epigenetic therapies in haematological malignancies: Current status and beyond. Seminars in Cancer Biology 51, 198-210
3) Gallipoli P, Cook A, Rhodes S, Hopcroft L, Wheadon H, Whetton AD, Jørgensen HG, Bhatia R & Holyoake TL (2014)
JAK2/STAT5 inhibition by nilotinib with ruxolitinib contributes to the elimination of CML CD34+ cells in vitro and in vivo. Blood 124, 1492-501.
4) Gallipoli P, Pellicano F, Morrison H, Laidlaw K, Allan EK, Bhatia R, Copland M, Jørgensen HG & Holyoake TL (2013)
Autocrine TNF-a production supports CML stem and progenitor cell survival and enhances their proliferation. Blood 122, 3335-9.
5) Gallipoli P, Stobo J, Heaney N, Nicolini FE, Clark R, Wilson G, Tighe J, McLintock L, Hughes T, Michor F, Paul J, Drummond M & Holyoake TL (2013)
Safety and efficacy of pulsed imatinib with or without G-CSF versus continuous imatinib in chronic phase CML patients at 5 years follow-up. British Journal of Haematology 163, 674-6.
6) Chen M*, Gallipoli P*, DeGeer D, Sloma I, Forrest DL, Chan M, Lai D, Jorgensen H, Ringrose A, Wang HM, Lambie K, Nakamoto H, Saw KM, Turhan A, Arlinghaus R, Paul J, Stobo J, Barnett MJ, Eaves A, Eaves CJ, Holyoake TL & Jiang X (2013)
Targeting Primitive Human Chronic Myeloid Leukemia Cells by Effective Inhibition of a New AHI-1-BCR-ABL-JAK2 Complex. Journal of the National Cancer Institute 105, 405-423. * joint first author
7)Gallipoli P, Shepherd P, Irvine D, Drummond M & Holyoake T (2011)
Restricted access to second generation tyrosine kinase inhibitors in the UK could result in suboptimal treatment for almost half of chronic myeloid leukaemia patients: results from a West of Scotland and Lothian population study. British Journal of Haematology 155, 128-130.