Nicole Soranzo
Email: ns545@cam.ac.uk
PA Name: Luisa Bellieni
PA Email: Luisa.bellieni@fht.org
Twitter: @nicolesoranzo
LinkedIn: https://www.linkedin.com/in/nicole-soranzo-25420a11
Biography
Nicole Soranzo is currently a Professor of Human Genetics at the University of Cambridge, Head of the Genomics Research Centre at Human Technopole (in Milano, IT) and an associate faculty at the Wellcome Sanger Institute (Hinxton, UK). After completing her degree in Biological Sciences at the University of Milan in 1994, she obtained her PhD in Genetics and Biotechnology at the University of Dundee, UK. From 1999 to 2002, she carried out post-doctoral research at the University of Milan, and from 2002 to 2005 at University College in London, where she applied human genetics to study human evolution. From 2005 to 2007 she worked as Senior Scientist at the Pharmacogenomics Department of Johnson and Johnson Pharmaceutical applying human genetics to improve drugs discovery and pharmacogenomics. She returned to the UK at the Sanger Institute, where she started her group in 2009. In 2013 she became adjunct faculty at the University of Cambridge School of Clinical Medicine, and in 2015 she was awarded a personal chair in Human Genetics. She has received many awards and honours for outstanding performance in science, including being appointed Fellow of the Academy of Medical Sciences (FMedSci) and European Molecular Organisation (EMBO).
Research Approach:
Understanding how genetic variation influences human traits and disease is one of the great challenges of modern biology and medicine. Our team uses high-resolution, population-scale genomic analyses of phenotypes representing different hierarchical levels of gene regulation, cellular and organismal phenotypes,to unravel these complex relationships.
Current projects:
Aetiology of complex human diseases
Over the last decade, we have contributed to international efforts to discover genetic determinants of quantitative risk factors and biomarkers of inflammation and immunity. These studies have discovered thousands of genetic loci, provided substantial new information on the general properties of the allelic architecture of these traits, and unravelled causal contributions to disease pathways. For these studies, we have applied genomic scans based on SNP arrays and whole-genome sequencing (UK10K Cohorts Project) to population-based cohorts, discovering rare genetic variation and causal pathways leading to several complex human disorders. Current projects focus on population-scale genome sequencing and analyses of complex diseases in Italy. For instance, we are part of the European consortium Genome of Europe funded by Digital Europe to derive reference genomes for representative samples of European variation. Funded in part by PNRR (PROMINENT project), we are investigating the genetic and environmental causes of chronic diseases and age-related conditions in several Italian cohorts.
Molecular and functional basis of human diseases of blood and immunity
We also use the power of other genomic technologies (e.g. transcriptomics, and epigenomics) to drive a greater understanding of themolecular and functional basis of diseases of blood and immunity. For instance, in the human genetic component of the high-impact EU BLUEPRINT Project, we completed the integrated analysis of high-resolution genetic, epigenetic and transcriptomic data in three major human immune cell types (CD14+ monocytes, CD16+ granulocytes and naive CD4+ T cells) in 200 healthy volunteers, and demonstrated genetic influences mediated by gene regulation at autoimmune disease loci. We are now applying a host of different approaches to advance understanding on the genetic control of blood cell formation, including large-scale surveys of RNA readouts in blood of thousands of healthy donors from multiple populations using single-cell RNA technologies, and the use of a host of in vitro techniques (eg. Massively parallel reporter assays and CRISPR screens) to test the function of human variation in diverse reference blood cell lines. A current project (Cardinal project), funded by the Chan Zuckerberg Initiative and the British Heart Foundation’s Centre of Research Excellence in Cambridge, UK, is generating the largest to date population-scale single cell genomics map in thousands of individuals from cohorts with linked biomedical data. We are currently leveraging this unprecedented dataset to discover genetic effects on gene expression and cell composition phenotypes, and to discover new determinants of health and disease at unprecedented resolution.
Therapeutic target prioritisation
We exploit multi-omic technologies to advance hypotheses of therapeutic target prioritisation for human diseases. Mapping of metabolic function changes associated with disease loci informs understanding of causal pathophysiological and molecular components of disease and can be applied to aid the prioritization of new biological targets in drug discovery programmes and repurposing existing drugs for new indications. Current efforts use rare loss-of-function (LoF) variation to study the phenotypic impact of inactivating established drug target genes. When carried by an otherwise healthy individual, these variants can provide evidence for safety of modulating that particular target to reduce disease risk.
Selected Publications
1. Astle, W.J., [45 authors], and Soranzo, N.± (2016) The allelic landscape of human blood cell trait variation and links to common complex disease. Cell 167;5;1415-1429.e19 https://www.sciencedirect.com/science/article/pii/S0092867416314635?via%3Dihub
2. Chen, L., [80 authors], and Soranzo, N.± (2016) Genetic drivers of epigenetic and transcriptional variation in human immune cells. Cell 167;5;1398-1414.e24 https://www.sciencedirect.com/science/article/pii/S0092867416314465?via%3Dihub
3. Vuckovic D., [110 authors] and Soranzo, N. (2020) The Polygenic and Monogenic Basis of Blood Traits and Diseases. Cell. 3;182(5):1214-1231.e11. https://www.sciencedirect.com/science/article/pii/S0092867420309995?via%3Dihub
4. Cai N., [26 authors], and Soranzo N. (2021) Mitochondrial DNA variants modulate N-formyl methionine, proteostasis and risk of late-onset human diseases. Nat Med. 27(9):1564-1575. https://www.nature.com/articles/s41591-021-01441-3
5. Guo J., [14 authors] and Soranzo N. (2024) Inherited polygenic effects on common haematological traits influence clonal selection on JAK2V617F and the development of myeloproliferative neoplasms. Nat Genet. 2024 Feb;56(2):273-280 https://www.nature.com/articles/s41588-023-01638-x
