- Higgs Group: Laboratory of Gene Regulation Research Group
DPhil, MRCP, FRCPath
I studied medicine at Oxford, before moving to London to undertake specialist training with an academic clinical fellowship in haematology and intensive care medicine. My clinical interests focus on bone marrow transplantation and cellular therapy. In 2012 I returned Oxford with a Wellcome Trust Clinical Research Training Fellowship to do a DPhil on gene regulation with Doug Higgs and Jim Hughes at the MRC Weatherall Institute of Molecular Medicine.
During my DPhil I developed a technique called Capture-C for detecting physical interactions between different sequences of DNA, within the chromatin fibre. This is more sensitive, accurate and reproducible than other available techniques and at present it is the best available technique for determining high-resolution chromatin interactions. This gave us key insights into the fundamental way in which physical interactions are controlled in the nucleus. Determining the physical interactions that occur in the nucleus is very important for understanding genome function. This is because the regulatory sequences are scattered over huge distances around the genes they control and detection of the physical contacts between different elements allows the regulatory elements controlling a gene to be identified. The technique should allow us to unravel the function of many of the polymorphisms identified by genome wide association studies that confer risk to common diseases such as multiple sclerosis, type II diabetes and malaria.
At present I am undertaking postdoctoral research and I am developing novel high throughput sequencing based techniques to allow safe genome editing of cells for cellular therapy and bone marrow transplantation.
HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis.
Yan T. et al, (2018), Nat Commun, 9
Robust detection of chromosomal interactions from small numbers of cells using low-input Capture-C.
Oudelaar AM. et al, (2017), Nucleic Acids Res, 45
Low-input Capture-C: A Chromosome Conformation Capture Assay to Analyze Chromatin Architecture in Small Numbers of Cells.
Oudelaar AM. et al, (2017), Bio Protoc, 7
Deficiency Drives Enhancer Activation of Oncogenes in Clear Cell Renal Cell Carcinoma.
Yao X. et al, (2017), Cancer Discov, 7, 1284 - 1305
Comparative analysis of three-dimensional chromosomal architecture identifies a novel fetal hemoglobin regulatory element.
Huang P. et al, (2017), Genes Dev, 31, 1704 - 1713