Description
The CAROLINA Project aims to gain an in-depth understanding of the biological mechanisms of ovarian aging and to develop innovative strategies to delay or prevent the age-related decline in reproductive function. This approach could pave the way for new therapies targeting age-related infertility and generate fundamental knowledge about the cellular, molecular, and epigenetic changes that characterize reproductive aging.
At its core, the project focuses on developing and optimizing partial cellular reprogramming in ovarian tissue and assessing its effects on gonadal function. Cellular reprogramming involves converting terminally differentiated somatic cells into pluripotent cells through the controlled expression of defined reprogramming factors. When applied in a partial and transient manner, this process can reverse cellular aging phenotypes without completely erasing the cell’s original identity, thereby preserving its specific functionality.
The specific objectives of the CAROLINA Project are:
- Develop and optimize protocols for partial reprogramming in the ovary, comprehensively evaluating their impact on ovarian function, follicular dynamics, and hormone production.
- Generate a comprehensive molecular atlas of ovarian cell types after partial reprogramming using high-resolution transcriptomics, epigenomics, and proteomics to identify key molecular and functional changes.
- Design an innovative perfusion-based approach for targeted delivery of reprogramming factors to human ovaries, with the goal of enhancing therapeutic efficacy while minimizing adverse effects such as loss of cell identity or activation of oncogenic pathways.
This project integrates reproductive biology, tissue engineering, stem cell biology, and omics technologies to address one of the greatest challenges in reproductive medicine: preserving and restoring female fertility in the context of aging.
Description
The CAROLINA Project aims to gain an in-depth understanding of the biological mechanisms of ovarian aging and to develop innovative strategies to delay or prevent the age-related decline in reproductive function. This approach could pave the way for new therapies targeting age-related infertility and generate fundamental knowledge about the cellular, molecular, and epigenetic changes that characterize reproductive aging.
At its core, the project focuses on developing and optimizing partial cellular reprogramming in ovarian tissue and assessing its effects on gonadal function. Cellular reprogramming involves converting terminally differentiated somatic cells into pluripotent cells through the controlled expression of defined reprogramming factors. When applied in a partial and transient manner, this process can reverse cellular aging phenotypes without completely erasing the cell’s original identity, thereby preserving its specific functionality.
The specific objectives of the CAROLINA Project are:
- Develop and optimize protocols for partial reprogramming in the ovary, comprehensively evaluating their impact on ovarian function, follicular dynamics, and hormone production.
- Generate a comprehensive molecular atlas of ovarian cell types after partial reprogramming using high-resolution transcriptomics, epigenomics, and proteomics to identify key molecular and functional changes.
- Design an innovative perfusion-based approach for targeted delivery of reprogramming factors to human ovaries, with the goal of enhancing therapeutic efficacy while minimizing adverse effects such as loss of cell identity or activation of oncogenic pathways.
This project integrates reproductive biology, tissue engineering, stem cell biology, and omics technologies to address one of the greatest challenges in reproductive medicine: preserving and restoring female fertility in the context of aging.
Team members
Xavier Santamaria M.D., Ph.D. is a Board Ob/Gyn specialist in Reproductive Medicine. He obtained a post-graduate fellowship in Reproductive Endocrinology and Infertility at Yale University (USA) and completed his Ph.D. at the Universitat Autònoma Barcelona (Spain). Dr. Santamaria was the Director of the International Department at the IVI between 2012 and 2016. In 2016, he joined Dr. Simon’s Research group as a Senior Principal Investigator, where he has developed his research related to Asherman’s Syndrome.
His main clinical and scientific interest is in understanding the regenerative capacity of the human endometrium and developing strategies to regenerate the endometrium to improve embryo implantation.
His group was the first to complete a trial using human bone marrow stem cells to treat Asherman’s syndrome and endometrial atrophy (PMID: 27005892) demonstrating this approach’s feasibility in treating endometrial pathologies. As a result, CD133+ cells have been designed as the first Orphan Drug (ODD) by the European Medicines Agency (EMA) and Food and Drug Administration (FDA) in the field of gynecological research. Dr. Santamaria has also participated as an inventor in 7 different patent applications, and is a co-founder and scientific director of 4 different start-up companies.
He has published 27 papers in peer-reviewed journals (H-index of 15) and 12 book chapters. He has been an invited speaker at more than 70 international conferences and was awarded the prize for Best Oral Presentation for Young Investigators at the Society of Gynecological Investigation Meeting in 2009. He has directed one doctoral thesis.
ResearcherID:Â D-7856-2018
Felipe Vilella, a Ph.D. in molecular biology, is the consolidated group leader of the Maternal Fetal Crosstalk Laboratory at INCLIVA/Carlos Simon Foundation. He performed two post-doctoral positions, one in the Clinical Science Centre of the MRC in London (UK) and the other in the Centro de Investigaciones Principe Felipe in Valencia (Spain). He was a visiting researcher for five years at Stanford University (USA) and two years at Harvard University (USA).
His main scientific interest focuses on understanding the communication mechanisms occurring between the mother and the embryo and elucidating how the mother can genetically modify the preimplantation embryo.
His research was the first to demonstrate the transmission of genetic information from the mother to the preimplantation embryo, demonstrating that the mother can modify the embryo transcriptomically and/or epigenetically, regardless of its genetic background (PMID: 26395145). He studied the effect of microRNAs and mitochondrial DNA secreted by endometrial cells on the embryo (PMID: 31665361, 29390102). He also focuses on understanding the implantation process, elucidating how endometrial cells communicate with each other at the single-cell level (PMID: 32929266).
He has published 42 papers in peer-reviewed journals with an accumulated impact factor of 399.35. His papers have been cited 2,267 times with an average of 56.68 citations/paper. He has an H-Index of 21, has published 12 book chapters, and has directed 6 Ph.D. theses. He has participated in over 16 international projects, being an independent principal investigator in 11. He has participated as an invited speaker at over 80 international conferences.
ResearchID: C-2970-2018. http://www.researcherid.com/rid/C-2970-2018
Ana Monteagudo, Ph.D.
Postdoctoral Researcher
Sofia Zaragozano
Predoctoral Researcher
Estefania Fernandez
Laboratory Technician