Skip to main navigationSkip to main content
The University of Southampton
Medicine
Phone:
01722 425193
Email:
A.J.Chase@soton.ac.uk

Dr Andrew Chase PhD

Associate Professor in Leukaemia Genetics

Dr Andrew Chase's photo

Dr Andrew Chase is an Associate Professor in Leukemia Genetics within the Faculty of Medicine at the University of Southampton.

Andrew has a background in clinical cytogenetics and early work focussed on cytogenetics of chronic myeloid leukaemia, the use of cytogenetics to monitor transplantation for CML, and chromosome breakage disorders.

Andrew is based at the Wessex Regional Genetics Laboratory in Salisbury and has a Bloodwise program grant with Professor Nick Cross. Recent work has used new genomic technologies to investigate the genetic changes that underlie chromosome rearrangements such as translocations and uniparental disomy in myeloid neoplasms. 

Qualifications

BSc, Botany, University of London, 1984
PhD, Cytogenetic and Molecular Characterisation of Chromosome 13 Abnormalities in Leukemia, Imperial College, University of London, 2000 

Appointments held

Senior Clinical Cytogeneticist, Hammersmith Hospital, London (1989-2001)
Principal Research Fellow (2001-2020)
Associate Professor (2020 – present)

 

Research interests

Dr. Andrew Chase is based at the Wessex Regional Genetics Laboratory in Salisbury. He has a Bloodwise program grant with Professor Nick Cross with the aim to of understand pathogenic mechanisms in myeloid neoplasms. A major interest has been the relationship between large scale chromosome rearrangements such as translocations and uniparental disomy and their pathogenic consequences at the DNA level in myeloid neoplasias.

Recent work has focussed on the potential for therapeutic targeting of tyrosine kinases in myeloid neoplasias, understanding the pathogenic role of STAT5B, EZH2 and PRR14L, and the consequences of ABL1 mutations in an inherited developmental disorder.

Therapeutic targeting with tyrosine kinase inhibitors. Chromosomal translocations and point mutations of tyrosine kinases can render cells constitutively active and potentially targetable by tyrosine kinase inhibitors. Cellular models were developed which demonstrated efficacy of ponatinib and dovitinib in targeting FGFR1 (Chase, 2007; Chase, 2013) and Ruxolitinib for targeting JAK2 (Chase, 2013; Schwaab, 2015).

STAT5B N642H and eosinophilia. A combination of RNAseq and whole exome sequencing datasets were used to identify myeloid neoplasms cases with STAT5B N642H mutations. A further screen of patient samples identified additional cases and showed the mutation to be associated with eosinophilia (Cross, 2019). Functional work is continuing to understand the link between the N642 mutation and eosinophilia and potential for therapeutic targeting using JAK2 inhibitors.

aUPD22 and PRR14L. A combination of SNP arrays and whole exome sequencing were used to identify inactivating mutations in PRR14L, primarily in chronic myelomonocytic leukaemia (CMML). PRR14L is therefore a novel tumour suppressor gene in myeloid neoplasias. Collaboration with Professor Jackie Boultwood and Dr. Andrea Pellagatti in Oxford showed that knockdown of PRR14L in primitive haemopoietic cells resulted in increased monocyte production consistent with the primary disease subtype of CMML (Chase, 2019). Work to further elucidate the normal function and pathogenic mechanisms of PRR14L is ongoing.

Pathogenic mechanisms of EZH2 mutations. Previous work showed that myeloid neoplasias can harbour inactivating mutations associated with acquired uniparental disomy of chromosome 7 (Ernst, 2010). Recent work has focussed on understanding the pathogenic consequences of a subset of missense mutations in EZH2 that lie in two clusters outside of the SET domain. An EZH2-null iPS cell line model was developed to show loss of activity in one cluster and RT-PCR and minigene assays were used to show induced exon skipping in a second cluster (Chase, 2020).

ABL1 mutations associated with a developmental disorder. Southampton clinical geneticists Andrew Douglas and Alexander Blakes have identified several patients with novel constitutional ABL1 mutations that give rise to developmental anomalies including skeletal malformations and congenital heart disease. Using techniques that were previously developed to investigate neoplasias with activating tyrosine kinase mutations, cell-based models of the ABL1 variants were used to investigate deregulation of ABL1 signalling and potential for treatment with the ABL1 inhibitor imatinib (Blakes, 2020).

 

Research group

Human Development and Health

Postgraduate Supervision

Co-supervision
Amy Jones PhD 2010
Sebastian Kreil PhD 2012

Sort via:TypeorYear

Articles

Letter/Editorial

MSC Genomics

Module Lead - Interpretation of Genomics in Clinical Practice
Dissertation Module supervisor
Lecturer

BM5

Subject Lead – Genetics
Tutorial facilitator
Year 3 project supervisor

 

Dr Andrew Chase
Wessex Regional Genetics Laboratory, Salisbury District Hospital

Room Number: WRGL/Salisbury

Share this profile Share this on Facebook Share this on Twitter Share this on Weibo
Privacy Settings