Research
Research in the lab focuses on the molecular basis of neurodegeneration. Our system of study is the neurotrophins and their receptors. Our neuronal population model is the cholinergic neurons from the basal forebrain. The human disease of our interest is Alzheimer's. We use molecular biology, biochemistry, flow cytometry, confocal and fluorescence microscopy together with histology and immunochemistry.
The neurotrophin receptors p75 and tropomyosin receptor kinase A (TrkA) play important roles in the development and survival of the nervous system. Biochemical data suggest that p75 and TrkA reciprocally regulate the activities of each other. For instance, p75 is able to regulate the response of TrkA to lower concentrations of nerve growth factor (NGF), and TrkA promotes shedding of the extracellular domain of p75 by α-secretases in a ligand-dependent manner. The current model suggests that p75 and TrkA are regulated by means of direct physical interaction; however, the nature of such interaction has been elusive thus far. Recently we found that the TMD of each receptor forms a direct complex, although the molecular mechanism is still unknown.
The current interests in our lab are:
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- The understanding of p75 neurotrophin receptor biological role in healthy and pathological aging. Our current focus is in the molecular mechanism and role of p75 cleavage by ADAM17 and the gamma-secretase complex.
- The understanding at molecular levels of how p75 and TrkA interact and regulate each other activities.
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- The understanding of NRTK activation mechanism, specially in NTRK fusions involved in tumor development and cancer.
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- To study the development and neurodegeneration of cholinergic neurons from the basal forebrain (BFCNs) during normal and pathological aging, with a focus on the transcriptional and epigenetic re-programming during aging.
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