Project description
The role of gender in kidney homeostasis and disease
Compared to males, females seem to be protected from kidney diseases including kidney cancer. This sexual dimorphism offers females an advantage against the age-related decline in renal function, which is the main cause of kidney disease. The EU-funded SIMPOSION project is working on the hypothesis that oestrogen signalling in renal progenitors supports their survival and self-renewal. Researchers will also test the rationale that the higher incidence of kidney cancer in males can be explained by lower renal progenitor numbers and a higher proliferation rate. Moreover, this sex hormone renal progenitor axis will be studied under the prism of pregnancy.
Objective
Kidney disorders represent a major global health burden with a significant sexual dimorphism that is largely unexplained. My group first identified the stem cells of the kidney (renal progenitors) and demonstrated their crucial role in kidney disease.
Here, I propose that sex hormones regulate number and function of renal progenitors to empower females to face the hemodynamic and metabolic challenges of pregnancy. I further propose that this process impacts on sexual dimorphisms in incidence and outcome of kidney diseases including kidney cancer. A multitude of unpublished data obtained with primary human progenitor cultures and unique mouse models of progenitor-specific sex hormones receptor knockout already support my concepts. I will demonstrate that, starting from the age of fertility, estrogen signaling in renal progenitors supports their survival and self-renewal, which is needed to increase their capacity to generate new podocytes and tubular epithelial cells. I will show that failure to produce a sufficient number of podocytes from estrogen-activated renal progenitors promotes preeclampsia and fetal growth retardation. This is a completely new pathophysiological concept of why women with a mismatch of nephron number and pregnancy-related hyperfiltration develop preeclampsia. I will further demonstrate that the same mechanism protects fertile women from severe forms of glomerular injury unrelated to pregnancy. Finally, I will prove that to compensate for the lower number of renal progenitors, testosterone pushes them to proliferate more in males and that this can explain the increased incidence of most prevalent forms of kidney cancer, that derive from renal progenitors. This topic is a direct continuation of my previous studies on renal progenitors supported by ERC Starting and Consolidator grants and will unravel fundamental paradigms in kidney physiology, adaptation, and disease with important implications for prevention and management of kidney disease.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- social sciences sociology demography fertility
- medical and health sciences clinical medicine obstetrics
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine physiology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-ADG - Advanced Grant
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Call for proposal
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(opens in new window) ERC-2020-ADG
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50121 Florence
Italy
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