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Senior Lecturer at Imperial College London
Understanding how genetic information is decoded to produce the complex regulatory systems driving disease remains a great challenge in biomedical sciences. However, the increasing availability of high-dimensional molecular, cellular and phenotypic data now allows a comprehensive investigation of the complex genetic and regulatory mechanisms that underlie the disease process.
My research lab focuses on the systems-level integration of genetic, functional genomic and phenotypic data to identify causal determinants and pathways of complex traits and disease, with a focus on cardio-metabolic, inflammatory and neuropsychiatric disorders. To this aim, I have developed an integrated genetic and gene-network approach, called Systems-Genetics, to determine the consequences of key genetic variants ('master genetic regulators') on functional gene-networks in disease. The research program in Systems-Genetics combines computational approaches and statistical modeling of high-throughput genomics and phenotyping of disease systems. In collaboration with world-leading laboratories, these approaches are applied to humans, animal model systems, and further integrated across species using comparative genomics, to provide a detailed map of the genetic control of functional gene-networks and pathways that are dysregulated in disease. Ultimately, the identification of primary genetic regulators of disease-associated functional networks will uncover novel determinants and therapeutic targets for complex diseases, which are not captured by traditional genetic strategies based on single-gene variant analysis.
To date, using Systems-Genetics we have uncovered several genes regulating functional gene-networks underling disease processes, including EBI2 regulating an anti-viral expression network and type 1 diabetes risk, KCNN4 and its co-regulatory network underlying cell multinucleation in inflammatory disease and SESN3 as a master genetic regulator of a proconvulsant gene network in human epileptic hippocampus. Our Systems-Genetics strategy will be further developed to study cardio-metabolic traits and disease, with the aim of deciphering the primary genetic factors and regulatory networks underlying hypertrophy, remodeling and fibrosis in the human heart.
INTEGRATIVE GENOMICS IN COMPLEX DISEASE
(*equal contribution, ¶corresponding author)
STRUCTURAL VARIANTS IN COMPLEX DISEASE
METHODS AND APPROACHES FOR SYSTEMS-GENETICS
SYSTEMS-GENETICS APPROACHES TO COMPLEX TRAITS AND DISEASE
Education2003 PhD in Biochemistry, Biology and Molecular Biotechnologies, University of Sassari (UNISS), Italy2000 MSc is Statistical Genetics, University of Pavia, Italy1998 Master Degree in Physical Chemistry, University of Sassari (UNISS), Italy
Professional Experience2012 Tenured Group Head, Medical Research Council (MRC)-Clinical Sciences Centre (CSC), UK2011 Senior Lecturer in Genomic Medicine, Imperial College London, UK2009 Associated Group Head, Medical Research Council (MRC)-Clinical Sciences Centre (CSC), UK2007 Lecturer in Genomic Medicine, Imperial College London, UK2003-2007 Career Development Fellowship (Statistical Geneticist), Imperial College London, UK2000-2003 Statistical Geneticist, Shardna Life Sciences Genomics Company, Italy1999 (Jun-Dec) Statistical Geneticist, C.N.R. Institute of Population Genetics, Italy
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