Dr Diana Moss PhD

Senior Lecturer Pharmacology & Therapeutics

Research

Neuroblastoma

Neuroblastoma is the most common individual solid tumour type in children. Survival rates for children presenting with metastatic Neuroblastoma remain very poor whereas tumours in the youngest patients may spontaneously differentiate leading to remission. We hypothesised that if tumours regress due to delayed differentiation, differentiation therapy may be a useful tool in the treatment of Neuroblastoma. We have shown that even the most aggressive tumours with amplification of the MYCN gene lose expression of MYCN and differentiate when placed in an embryonic environment. Current interests include the use of a chick embryo chorioallantoic membrane model as an in vivo system to develop differentiation therapies. Neuroblastoma cells will form tumours on the chick CAM and these can be treated with drugs such as retinoic acid. In response tumours display an increase in differentiation markers and a decrease in stem cell markers. Neuroblastoma cells grown in normoxia do not metastasise into the embryo however cells grown in hypoxia for three days do metastasise. We are also interested in the ability of differentiation therapies to limit the metastasis of Neuroblastoma cells.

Control of gene regulation in diseases of the nervous system

Polymorphisms or mutations leading to disregulation of gene expression may be crucial for understanding the causes of diseases of the nervous system, rather than mutations within the coding region of proteins. Putative regulatory domains are identified using comparative genomics and their activity is tested in vitro and then in vivo using the technique of electroporation of chick embryos. We have investigated the role of evolutionary conserved regions (ECRs) of genes implicated in motor neuron disease in this model. Interestingly, recently identified primate specific SVA’s associated with the FUS gene are also active in the neural tube of chick embryos suggesting the trans acting elements that act on these sequences are conserved back to chick.

Research Grants

Exploiting the embryonic environment to reprogram cancer stem cells in neuroblastoma

NEUROBLASTOMA (UK)

October 2008 - September 2012

Analysis of the expression, protein-protein interactions and function of members of the IgLON family of neuronal glycoproteins.

WELLCOME TRUST (UK)

April 2000 - November 2003

Advanced in vivo imaging and transcriptomic analysis of neuroblastoma metastasis in a chick embryo model

NEUROBLASTOMA (UK)

October 2014 - February 2018

Do IgLONs regulate cell division in glial cells?

WELLCOME TRUST (UK)

June 2004 - July 2004

Consequence of down regulation of MYCN in Neuroblastoma cells in a chick chorioallantoic membrane tumour model: Vacation scholarship for Xinwei Chen

WELLCOME TRUST (UK)

July 2013 - September 2013

Mechanism and consequences of MYCN down regulation in neuroblastoma cells in vivo and in vitro

NEUROBLASTOMA (UK)

October 2012 - April 2014

New model to investigate regulation of expression of key genes responsible for pain modulation

PAIN RELIEF FOUNDATION (UK)

September 2009 - August 2010

An investigation into the role of the lgLON family of cell adhesion molecules in gliomas and other brain tumours.

NORTH WEST CANCER RESEARCH FUND

December 2003 - November 2004

How does the embryonic environment control MYCN expression in neuroblastoma cells?

NEUROBLASTOMA RESEARCH FUND (UK)

May 2012 - May 2013

Role of hypoxia in paediatric tumour cells migration, adhesion and invasion

ALDER HEY CHILDREN'S NHS FOUNDATION TRUST (UK)

June 2013 - September 2014

Bench fees for Mohammed Akeel

KING ABDULAZIZ CITY FOR SCIENCE AND TECHNOLOGY (KACST) (SAUDI ARABIA)

October 2012 - May 2013

An investigation into the role of the lgLON family of cell adhesion molecules in gliomas and other brain tumours.

CLATTERBRIDGE CANCER RESEARCH

December 2004 - December 2005

Bench fees for Rasha Swadi

REPUBLIC OF IRAQ MINISTRY OF EDUCATION

October 2014 - September 2018

Prediction and analysis of genetic variation which would affect expression of candidate genes associated with Motor Neurone Disease

MOTOR NEURONE DISEASE ASSOCIATION

September 2009 - May 2011

Establishment of a lent viral system

ALDER HEY CHILDREN'S CHARITY (UK)

January 2014 - February 2014

Research Collaborations

John Quinn

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Violaine See

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Paediatric Cancer Biology

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