Dr Gabriele Migliorini
Postdoctoral Research Scientist in Statistical Functional Genomics
Functional Genomics of Ankylosing Spondylitis
The majority of regulatory variants identified by Genome-Wide Association Studies (GWAS) occur in non-coding regions of the genome, often at considerable distances from the nearest gene.
A recent GWAS study on Ankylosing Spondylitis (AS), a severe arthropathy involving the spine and sacroiliac joints, identifies, for example, the association with the Major Histocompatibility Complex (MHC) and HLA-B27, as well as several, non-MHC loci, many of which are in intergenic regions.
Methods for assaying chromatin conformation have been recently proposed to identify regulatory regions and enumerate pair-wise interactions that regulatory regions establish to control gene expression, often from distances of the order of tens to thousands of kilobase pairs.
I apply such methods to link specific genes to disease associated variants that have been previously identified by GWAS studies. In particular, I devise bioinformatics protocols to process data obtained by high-throughput sequencing methods used in our Lab, such as ATAC-seq, and Capture-C.
These methods quantitatively identify regulatory regions and assess physical proximity profiles across the genome, effectively imaging the features of DNA folding at kilobase resolution and possibly unveiling the mechanisms involved in the disease pathogenesis of AS and beyond.
I have a PhD in Physics gained at the MIT, Boston, USA. During the last years of my PhD I studied polymer physics, a key component to understand the main ideas behind Chromosome Conformation methods.
During my postdoctoral experience, part of which was at the Max Planck Institute for Polymer Research, I was introduced to the ideas and methods behind chromatin folding, getting acquainted with computational methods and techniques I currently employ in my research.
I recently joined the Julian Knight group at Wellcome Trust Centre for Human Genetics after working for the last five years at the Institute of Cancer Research, University of London.
Correction: Author Correction: Genetic and regulatory mechanism of susceptibility to high-hyperdiploid acute lymphoblastic leukaemia at 10q21.2
Studd JB. et al, (2018), Nature Communications, 9
Identification of 19 new risk loci and potential regulatory mechanisms influencing susceptibility to testicular germ cell tumor
Litchfield K. et al, (2017), Nature Genetics, 49, 1133 - 1140
Genetic and regulatory mechanism of susceptibility to high-hyperdiploid acute lymphoblastic leukaemia at 10q21.2
Studd JB. et al, (2017), Nature Communications, 8
Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
Mitchell JS. et al, (2016), Nature Communications, 7
Genetic Predisposition to Chronic Lymphocytic Leukemia Is Mediated by a BMF Super-Enhancer Polymorphism
Kandaswamy R. et al, (2016), Cell Reports, 16, 2061 - 2067