Description
The CAROLINA Project aims to understand ovarian aging mechanisms and develop novel strategies to delay or prevent reproductive aging. This project may lead to new therapies for infertility caused by ovarian aging and provide insights into the cellular and molecular changes associated with reproductive aging.
We aim to develop and optimize partial reprogramming in the ovary and assess the effects on ovarian function. Cellular reprogramming enables the conversion of terminally differentiated somatic cells into pluripotent cells using the expression of defined reprogramming factors [1][2]. During induced cell fate alteration, cellular reprogramming reverses cellular phenotypes linked to aging [3][4][5].
The CAROLINA Project has specific objectives to achieve this goal, including:
- Developing and optimizing partial reprogramming in the ovary and analyzing changes in ovarian function
- Generating a molecular roadmap of ovarian cell types following partial reprogramming to understand alterations at the molecular level
- Developing a perfusion-based approach to deliver reprogramming factors and rejuvenate human ovaries, which will enhance efficiency and reduce off-target effects.

Description
The CAROLINA Project aims to understand ovarian aging mechanisms and develop novel strategies to delay or prevent reproductive aging. This project may lead to new therapies for infertility caused by ovarian aging and provide insights into the cellular and molecular changes associated with reproductive aging.
We aim to develop and optimize partial reprogramming in the ovary and assess the effects on ovarian function. Cellular reprogramming enables the conversion of terminally differentiated somatic cells into pluripotent cells using the expression of defined reprogramming factors [1][2]. During induced cell fate alteration, cellular reprogramming reverses cellular phenotypes linked to aging [3][4][5].
The CAROLINA Project has specific objectives to achieve this goal, including:
- Developing and optimizing partial reprogramming in the ovary and analyzing changes in ovarian function
- Generating a molecular roadmap of ovarian cell types following partial reprogramming to understand alterations at the molecular level
- Developing a perfusion-based approach to deliver reprogramming factors and rejuvenate human ovaries, which will enhance efficiency and reduce off-target effects.

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

Sara Lopez, Ph.D.

Ana Monteagudo, Ph.D.

Sofia Zaragozano

Ana Ochando
