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Gestobes: Metabolism Regulation
The research team led by Dr. Mª del Pilar Ramos was established as a research group in 1997 at the Faculty of Pharmacy of the Universidad CEU-San Pablo. They have extensive experience in studying metabolic adaptations and their regulation by insulin in physiological situations such as pregnancy, or pathological conditions such as obesity or gestational diabetes.
Dr. Ramos, a professor of Biochemistry and Molecular Biology, has been working for over 30 years in the field of insulin signaling and oxidative/nitrosative stress. She has secured public funding (PM99/011, BFI2003-03455, SAF2007-64881, SAF2010-19603, SAF2014-56671-R, RTI2018-095615-B-I00, and PID2021-123865OB-I00) and consortium grants (S2010/BMD-2423 -MOIR1, B2017/BMD3684-MOIR2, and P2022/BMD-7227-MOIR3) as well as private funding (FUSP-CEU, and director of the Merck Biotechnology Chair), resulting in over 80 publications. She has served on the board of the Diabetic Pregnancy Study Group (DPSG) and was its president in 2017 and 2018. She has also coordinated the Perinatal Biochemistry group of the SEBBM (2010-2014). Additionally, the IP has participated in numerous internationally funded research projects, including European calls, focusing on studying adaptations during pregnancy, the molecular mechanisms of these adaptations, and their implications for fetal development. To carry out these projects, the research group has established a wide range of Biochemistry and Molecular Biology technologies in studies using cellular models, animals (genetically modified mice, rats), and humans, currently collaborating with Dr. José Luis Bartha from the La Paz Hospital.
Additionally, Dr. Ramos has supervised 7 doctoral theses and has overseen numerous research projects for obtaining the Advanced Studies Diploma. Her research work is complemented by her roles as a lecturer and manager at the Universidad CEU-San Pablo, where she is responsible for the area of Biochemistry and Molecular Biology and Vice Dean of Organization and Resources, Faculty, Teaching, and Research at the Faculty of Pharmacy, USP-CEU. She previously served as Director of the Degree in Biotechnology at the same Faculty and, since 2019, she has been President of the Conference of Coordinators of Bachelor's and Master's Degrees in Biochemistry and Biotechnology at Spanish Universities and director of the Master's Degree in Management of Biotechnological Health Companies (in collaboration with ASEBIO, Spanish Association of Bioenterprises). Dr. Ramos is a frequent speaker and moderator at national and international conferences.
As a result of her career, Dr. Ramos has received various awards, including the "11th Joseph Hoet Research Award" from the "Diabetic Pregnancy Study Group (DPSG)" of the EASD in 2014. The award, sponsored by Novo-Nordisk, is given for outstanding research contributions in the field of Diabetes and Pregnancy.
Key Features of the Research Group:
Insulin resistance is a characteristic of various physiological conditions (pregnancy, aging) or pathological conditions such as obesity, type 2 diabetes (T2DM), or metabolic syndrome. In recent years, changes in lifestyle have contributed to the increased prevalence of pathologies associated with insulin resistance, with an estimated 300 million people projected to have T2DM by 2025. The association in middle age between metabolic syndrome disorders and subsequent neurodegenerative disorders, including Alzheimer's disease and Parkinson's, is well documented. An important mechanism in the connection between metabolic syndrome and neurodegenerative disorders is chronic inflammation associated with metabolic disorders (metaflammation), which underlies persistent neuroinflammation and subsequent neurodegeneration. The growing worldwide prevalence of obesity, diabetes, and Alzheimer's disease has a significant socioeconomic impact and represents a major challenge for public health systems. For this reason, the WHO strongly recommends efforts to prevent Alzheimer's disease by introducing changes in modifiable risk factors such as diet.
In this context, the GESTOBES group has been studying the molecular mechanisms and intertissue communication in insulin resistance and its implications in metabolism for years. In this line, we have recently made relevant contributions suggesting that PTN (pleiotrophin) regulates both metaflammation - associated with insulin resistance and altered lipid accumulation in conditions such as aging, pregnancy, and obesity - and the neuroimmune response in central disorders characterized by manifest neuroinflammation. Based on these findings, our working hypothesis is that the PTN/RPTPβ/ζ signaling pathway links neuroinflammation and neurodegeneration with peripheral metaflammation inherent in metabolic syndrome disorders such as obesity, glucose intolerance, or dyslipidemia. To test this hypothesis, we will use a diet-induced obesity model to study whether Ptn deletion is associated with neuroinflammation and neurodegeneration and whether its receptor, RPTPβ/ζ, is involved in these effects. Additionally, we will investigate whether Ptn deletion affects neuroinflammation and neurodegeneration in a mouse model of Alzheimer's disease. Our work will benefit from the tools we have successfully used to describe the functions of PTN and RPTPβ/ζ in inflammatory pathologies and conditions (in vitro and in vivo models including PTN and APP GEMMs, specific RPTPβ/ζ inhibitors, etc.).
Funding over the Last Five Years:
Contracts with Companies
Dr. Ramos, a professor of Biochemistry and Molecular Biology, has been working for over 30 years in the field of insulin signaling and oxidative/nitrosative stress. She has secured public funding (PM99/011, BFI2003-03455, SAF2007-64881, SAF2010-19603, SAF2014-56671-R, RTI2018-095615-B-I00, and PID2021-123865OB-I00) and consortium grants (S2010/BMD-2423 -MOIR1, B2017/BMD3684-MOIR2, and P2022/BMD-7227-MOIR3) as well as private funding (FUSP-CEU, and director of the Merck Biotechnology Chair), resulting in over 80 publications. She has served on the board of the Diabetic Pregnancy Study Group (DPSG) and was its president in 2017 and 2018. She has also coordinated the Perinatal Biochemistry group of the SEBBM (2010-2014). Additionally, the IP has participated in numerous internationally funded research projects, including European calls, focusing on studying adaptations during pregnancy, the molecular mechanisms of these adaptations, and their implications for fetal development. To carry out these projects, the research group has established a wide range of Biochemistry and Molecular Biology technologies in studies using cellular models, animals (genetically modified mice, rats), and humans, currently collaborating with Dr. José Luis Bartha from the La Paz Hospital.
Additionally, Dr. Ramos has supervised 7 doctoral theses and has overseen numerous research projects for obtaining the Advanced Studies Diploma. Her research work is complemented by her roles as a lecturer and manager at the Universidad CEU-San Pablo, where she is responsible for the area of Biochemistry and Molecular Biology and Vice Dean of Organization and Resources, Faculty, Teaching, and Research at the Faculty of Pharmacy, USP-CEU. She previously served as Director of the Degree in Biotechnology at the same Faculty and, since 2019, she has been President of the Conference of Coordinators of Bachelor's and Master's Degrees in Biochemistry and Biotechnology at Spanish Universities and director of the Master's Degree in Management of Biotechnological Health Companies (in collaboration with ASEBIO, Spanish Association of Bioenterprises). Dr. Ramos is a frequent speaker and moderator at national and international conferences.
As a result of her career, Dr. Ramos has received various awards, including the "11th Joseph Hoet Research Award" from the "Diabetic Pregnancy Study Group (DPSG)" of the EASD in 2014. The award, sponsored by Novo-Nordisk, is given for outstanding research contributions in the field of Diabetes and Pregnancy.
Key Features of the Research Group:
Insulin resistance is a characteristic of various physiological conditions (pregnancy, aging) or pathological conditions such as obesity, type 2 diabetes (T2DM), or metabolic syndrome. In recent years, changes in lifestyle have contributed to the increased prevalence of pathologies associated with insulin resistance, with an estimated 300 million people projected to have T2DM by 2025. The association in middle age between metabolic syndrome disorders and subsequent neurodegenerative disorders, including Alzheimer's disease and Parkinson's, is well documented. An important mechanism in the connection between metabolic syndrome and neurodegenerative disorders is chronic inflammation associated with metabolic disorders (metaflammation), which underlies persistent neuroinflammation and subsequent neurodegeneration. The growing worldwide prevalence of obesity, diabetes, and Alzheimer's disease has a significant socioeconomic impact and represents a major challenge for public health systems. For this reason, the WHO strongly recommends efforts to prevent Alzheimer's disease by introducing changes in modifiable risk factors such as diet.
In this context, the GESTOBES group has been studying the molecular mechanisms and intertissue communication in insulin resistance and its implications in metabolism for years. In this line, we have recently made relevant contributions suggesting that PTN (pleiotrophin) regulates both metaflammation - associated with insulin resistance and altered lipid accumulation in conditions such as aging, pregnancy, and obesity - and the neuroimmune response in central disorders characterized by manifest neuroinflammation. Based on these findings, our working hypothesis is that the PTN/RPTPβ/ζ signaling pathway links neuroinflammation and neurodegeneration with peripheral metaflammation inherent in metabolic syndrome disorders such as obesity, glucose intolerance, or dyslipidemia. To test this hypothesis, we will use a diet-induced obesity model to study whether Ptn deletion is associated with neuroinflammation and neurodegeneration and whether its receptor, RPTPβ/ζ, is involved in these effects. Additionally, we will investigate whether Ptn deletion affects neuroinflammation and neurodegeneration in a mouse model of Alzheimer's disease. Our work will benefit from the tools we have successfully used to describe the functions of PTN and RPTPβ/ζ in inflammatory pathologies and conditions (in vitro and in vivo models including PTN and APP GEMMs, specific RPTPβ/ζ inhibitors, etc.).
Funding over the Last Five Years:
- [2022-2026] MINISTRY OF SCIENCE AND INNOVATION. Connection of metabolic syndrome and metainflammation with neuroinflammation and neurodegeneration through signaling pathways. (PID2021-123865OB-I00). PI: María del Pilar Ramos/Gonzalo Herradón.
- [2023-2026] COMMUNITY OF MADRID. Advancing in the knowledge of new mediators, mechanisms, and tissue interactome in situations of insulin resistance. S2022/BMD-7227. PI: María del Pilar Ramos. Coord. Gema Medina.Gómez.
- [2020-2023] MINISTRY OF HEALTH, CONSUMER AFFAIRS AND SOCIAL WELFARE. NATIONAL DRUG PLAN. The axis as a regulator of neuroinflammation induced by alcohol consumption during adolescence. (PND 2019/015). PI: Dr. Gonzalo Herradón.
- [2019-2021] MINISTRY OF SCIENCE, INNOVATION AND UNIVERSITIES. Role of the pleiotrophin/tyrosine phosphatase beta/zeta signaling pathway in inflammatory processes involved in metabolic and neurodegenerative disorders. (RTI2018-095615-B-I00). PI: Dr. María del Pilar Ramos Álvarez.
- [2018-2022] COMMUNITY OF MADRID. Molecular mechanisms and intertissular communication in insulin resistance. S2017/BMD-3684. PI: María del Pilar Ramos. Coord. Gema Medina.Gómez.
Contracts with Companies
- [2015-present] Merck Biotechnology Chair. Director: Dr. María del Pilar Ramos Álvarez.