Molecular genetics of renal disorders
Irene Franco
Email: franco.irene@hsr.it
Location: DIBIT1 A2, Floor 4, Room 40
Project Leader, Somatic mutation mechanisms lab
Staff scientist, Molecular Genetics of Renal Disorders Unit
Irene Franco holds a PhD in Human Oncology (2014) and an MS in Biotechnology (2009) from the University of Torino (Italy), where she studied cellular signaling in different physio-pathological contexts, including inflammation, embryonic development and polycystic kidney disease. In 2014, she moved to the Karolinska Institute (Sweden), where she used next generation sequencing to study genetic mechanisms of aging. In 2020, she has obtained a Horizon2020 Marie-Curie individual fellowship to move to San Raffaele and develop her research on mechanisms of somatic mutagenesis in the kidney. She has now obtained independent financing from AIRC and Fondazione Cariplo to study somatic mutagenesis in the context of kidney cancer and polycystic kidney disease.
Research activity
Exposure to exogenous and endogenous mutagens results in the daily accumulation of somatic mutations. The consequent loss of genomic integrity is recognized as the leading force in malignant transformation. Despite this important role, our understanding of ongoing mutagenic processes in healthy tissues and cell types is limited.
Our research focuses on somatic mutagenesis in normal tissues, in particular, in pre-cancerous kidney cells. Through analysis of somatic cells taken from human kidneys as well as the use of mouse models, we are investigating molecular mechanisms that may lead to an excessive accumulation of somatic mutations. In particular, through a multidisciplinary approach that combines cellular biology and genomics, we are evaluating whether changes in cellular metabolism may promote mutagenesis and consequently act as a very early trigger of cellular transformation. In addition, we are exploring somatic mutagenesis in kidney samples from patients with inherited diseases that cause cancer predisposition and polycystic kidney disease. Results obtained by this study are expected to provide a better understanding of kidney cancer initiation and possible strategies for prevention of kidney tumors and cysts in individuals at risk.
The complete list of publications is available here.
Franco I., Eriksson M., Reverting to old theories of aging with new evidence for the role of somatic mutations, Nature Review Genetics, 2022, 645-646.
Franco I., Revechon G., Eriksson M., Challenges of proving a causal role of somatic mutations in the aging process, Aging Cell, 2022; 21:e13613
Margaria JP, Campa CC, De Santis MC, Hirsch E. and Franco I, ThePI3K/Akt/mTOR pathway in polycystic kidney disease: a complex interaction with polycystins and primary cilium., Cellular Signalling, 2020 Feb;66:109468. doi: 10.1016/j.cellsig.2019.109468
Franco I., Helgadottir H.T., Moggio A., Larsson M., Vrtačnik P., Johansson A., Norgren N., Lundin P., Mas-Ponte D, Nordström J., Lundgren T., Stenvinkel P., Wennberg L., Supek F. and Eriksson M., Whole genome DNA sequencing provides an atlas of somatic mutagenesis in healthy human cells and identifies a tumor-prone cell type, Genome Biology, 2019 Dec 18;20(1):285. doi: 10.1186/s13059-019-1892-z
Franco, I., Fernandez-Gonzalo R., Vrtacnik, P., Lundberg, T. R., Eriksson, M., Gustafsson, T., Healthy skeletal muscle aging: The role of satellite cells, somatic mutations and exercise, Int Review of Cell and Molec Biology, 2019, 346 157-200
Franco I, Johansson A, Olsson K, Vrtačnik P, Lundin P, Helgadottir HT, Larsson M, Revêchon G, Bosia C, Pagnani A, Provero P, Gustafsson T, Fischer H, Eriksson M., Somatic mutagenesis in satellite cells associates with human skeletal muscle aging, Nature Communications, 2018 Feb 23;9(1):800.
Revêchon G, Viceconte N, McKenna T, Sola Carvajal A, Vrtačnik P, Stenvinkel P, Lundgren T, Hultenby K, Franco I, Eriksson M., Rare progerin-expressing preadipocytes and adipocytes contribute to tissue depletion over time, Scientific Reports, 2017 Jun 30;7(1):4405.
Franco I, Margaria JP, De Santis MC, Ranghino A, Monteyne D, Chiaravalli M, Pema M, Campa CC, Ratto E, Gulluni F, Perez-Morga D, Somlo S, Merlo GR, Boletta A, Hirsch E., Phosphoinositide 3-Kinase-C2α Regulates Polycystin-2 Ciliary Entry and Protects against Kidney Cyst Formation, Journal of the American Society of Nephrology, 2016 Apr;27(4):1135-44.