Studying normal and abnormal haematopoiesis through the human lifetime
Research type
Research Study
Full title
Studying normal and abnormal haematopoiesis through the human lifetime by molecular and functional characteristation, and genetic modifications.
IRAS ID
273782
Contact name
Anindita Roy
Contact email
Sponsor organisation
University of Oxford
Duration of Study in the UK
10 years, 0 months, 0 days
Research summary
Haematopoiesis is the process by which stem cells (haematopoietic stem cells, HSCs), develop stepwise through immature, progenitor cell types to mature blood cells. This starts before birth and continues throughout the human lifetime. Currently, much of our understanding of haematopoiesis comes from studies in mice; this shows variation by developmental age and tissue site. These findings cannot be fully extrapolated to humans, therefore detailed characterisation of human haematopoiesis before birth, and comparison to haematopoiesis during childhood and adulthood is crucial.
We need to understand how abnormal haematopoiesis leads to blood disorders such as blood cancer (leukaemia). Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer. The origin of many of these disorders depends on the developmental stage of cell it develops in. In infants and children, leukaemia frequently arises from changes in white blood cell development before birth. Some subtypes of childhood leukaemia, such as infant-ALL (diagnosed in babies <1 year of age) and those occurring in children with Down syndrome (DS-ALL), have a poor outcome. Studying prenatal and postnatal blood cells will determine the specific characteristics of immature fetal target cells and their microenvironment that make them susceptible to cancer causing changes, By genetically modifying prenatal and postnatal target cells, specific blood cancers such as infant leukaemia may be modelled in order to understand their biology, and to test novel treatments. Conversely genetic modification of leukaemic blood cells may identify targets for treatments.
This project aims to investigate:
1: How blood cell development changes through normal human lifetime
2: How disruption of normal blood cell development leads to blood disorders
3: Can normal blood cells be genetically modified to model blood disorders such as leukaemia, especially those that arise in infants and children?
4: Can abnormal cells be genetically modified to identify treatments of blood disorders?REC name
London - Bloomsbury Research Ethics Committee
REC reference
21/LO/0195
Date of REC Opinion
9 Mar 2021
REC opinion
Favourable Opinion