FeMCa
Feeding Circuits and Mechanisms of Cancer

Research Line 1 - Neuron-Glia Interactions in the Control of Energy Homeostasis.

It has been demonstrated that the connectivity of hypothalamic circuits related to intake is not rigidly established but shows predictable changes in response to circulating levels of metabolic hormones. When these dynamic synaptic changes are correlated with the behavioral effects of different signals, it becomes evident that the induced synaptic remodeling precedes changes in the behavior of the animals. This suggests that the synaptic plasticity of hypothalamic circuits, governed by peripheral metabolic signals, is a prerequisite for appropriate behavioral and autonomic adaptations to the changing peripheral environment.

In recent years, our understanding of the function of glial cells in the brain has evolved significantly. Their role in various aspects of the control of neural circuits has been recognized. Astrocytes, in particular, have been linked to both pre- and postsynaptic control of neuronal transmission through multimodal actions. In the hypothalamus, astrocytes and microglia regulate the organization of synaptic inputs and the activity of neural circuits that affect feeding, energy metabolism, and glucose homeostasis. Hypothalamic neurons have been shown to directly stimulate neighboring astrocytes, revealing neuron-to-astrocyte communication in the physiological adaptations to changes in energy state.

Our main objective is to identify the different underlying mechanisms in hypothalamic neuron-glia communication involved in the control of intake behaviors, as well as the intracellular events triggered in response to changes in metabolic signals across various cell types in the hypothalamus.

Research Line 2 - Study of the Molecular Processes Involved in Thyroid Cancer.

Cancer is one of the major unresolved problems in our society. A comprehensive and sustained response to targeted therapies remains difficult to achieve for most types of cancer due to the development of resistance. The identification of targets that can predict treatment response is key to designing improved therapeutic strategies that prevent tumor recurrence.

Thyroid cancer is the most common endocrine cancer, and its incidence has inexplicably increased in recent years. It is diagnosed more frequently in women than in men, being the fifth most common type of cancer among women according to WHO (2020), while it ranks eighteenth among men. In young women (under 25 years), it becomes the most prevalent cancer. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, with a relatively good prognosis following tumor resection or radioactive iodine uptake. However, a percentage of cases may progress and metastasize, becoming untreatable. Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC), although rare (6% and 1%, respectively), are highly aggressive and have an extremely unfavorable prognosis. So far, there is no effective treatment for PDTC and ATC.

The MAPK pathway is the most altered pathway in cancer, including thyroid cancer. Most cases present mutations in BRAF, followed by mutations in RAS (NRAS >> HRAS > KRAS). Treatment with MAPK pathway inhibitors initially provides significant therapeutic benefits in patients with BRAFV600E mutations; however, tumors almost universally return with a more aggressive phenotype.

Our objective is to investigate the molecular mechanisms involved in the initiation of thyroid tumors and the progression of the disease through multidisciplinary approaches, including genetic, biochemical, and cellular biological methods. We aim to understand the functional consequences of key disease factors and identify new potential targets and dependency-based approaches to discover new therapies. One of the central research lines in the laboratory is the study of the role of the HIPPO/YAP pathway in thyroid cancer and in resistance to monotherapy.