Institute of Genetic Medicine

Staff Profile

Dr Colin Miles

Senior Lecturer

Background

Colin Miles is a geneticist and developmental biologist, formerly of MRC Human Genetics Unit (Edinburgh) and MRC National Institute for Medical Research (London) with particular interests in nephrogenesis and haematopoiesis, and the creation of models of human disease for dissecting disease mechanisms and identifying/testing novel therapeutic approaches.

Research

Research Interests

The Wilms’ Tumour 1 Gene in Development and Disease.

Mutations in the Wilms’ tumour suppressor gene, WT1, cause kidney disease, childhood kidney cancer and leukaemia. In addition, WT1 is crucial for many other aspects of normal mammalian development and serves as a paradigm for aberrant development leading to human disease. To date, however, few bona fide target genes have been identified and the molecular pathways in which WT1 acts in normal development and disease remain poorly characterised. Research in my laboratory employs transgenic/gene targeting technology coupled with genomics/proteomics approaches to study the regulation and function of the WT1 gene during development in order to dissect the molecular and cellular mechanisms underlying these processes.


Glomerulosclerosis is a key and common feature of chronic kidney disease (over 140,000 affected in UK). WT1 mutation causes diffuse glomerulosclerosis in a rare condition known as Denys Drash Syndrome (DDS). We are identifying the initiating molecular and cellular events leading to glomerulosclerosis in a DDS model and building a molecular profile of disease progression in this model with a view to identifying novel diagnostic markers/potential therapeutic targets that may be relevant to the progression of glomerulosclerosis in general.


Expression of WT1 is a hallmark of the majority of all leukaemias. Consequently, WT1 is an attractive target for pan-leukaemic therapies. Although WT1 is readily detected in leukaemic cells, it has proven difficult to identify WT1 expressing cells in normal, healthy, bone marrow and therefore the normal physiological role of WT1 expressing cells and the function of WT1 remain unknown. If anti-WT1 strategies are to provide effective therapies, without adverse side-effects, it is essential to understand the role of WT1 and WT1 expressing cells in normal haematopoiesis. We are developing novel approaches to characterise WT1 expressing haematopoietic cells and dissect the role of WT1 within these cells.


In addition, the frequency of WT1 mutation in acute myeloid leukaemia (AML) is similar to that in Wilms’ tumour, implying that mutation of WT1 is a leukaemogenic event. We are creating and analysing models designed to mimic the situation in leukaemia to determine the role of WT1 mutation in leukaemia and the function of WT1 in normal haematopoiesis.

Co-workers

John Sayer - Clinical Professor of Renal Medicine 

Simon Ramsbottom - Kidney Research UK Postdoctoral Fellow

Elisa Molinari - Postdoctoral Research Associate

Sumaya Alkanderi - Clinical Research Associate

Ahzad Ahmad - Clinical Research Associate

Laura Devlin - PhD student

Laura Powell - PhD student

 

Teaching

MRes Module Leader for Genetic Medicine (MMB8030)

Contributor to Developmental Genetics MRes module (MMB8031) and Undergraduate module Genetics of Development and its Disorders (BGM3062)

Publications