Research
We have been working with different biological systems but focusing on the structural aspects of three macromolecular assemblies: the troponin complex of the cardiac contraction system and the amyloidogenic proteins alpha-synuclein and p53 participating in senile disorders and cancer, respectively. We combine structural and biophysical approaches, including nuclear magnetic resonance, cryo-EM, small angle X-ray scattering, fluorescence, and image correlation spectroscopy, to help understand fundamental questions in biology.
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The cardiac contraction-relaxation cycle is controlled by sophisticated machinery. Striated muscle contraction relies on the interaction between two filamentous systems, the thick filament comprised of myosin and the thin filament (TF) composed of filamentous actin (F-actin), tropomyosin (Tm), and the Tn complex. In the heart, the Tn-complex, a trimer comprised of troponin C (cTnC), troponin T (cTnT), and troponin I (cTnI), is situated at regular intervals along the TF and is responsible for calcium-dependent positioning of Tm upon the surface of F-actin. We now witness allostery as a critical mechanism to explain the functioning of macromolecular events. We are interested in better understanding allosteric networks' role in the physiology of cardiac muscle contraction and disease.
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Amyloid filaments are found in diverse senile disorders and, more recently, in cancer as amyloid-like species. Amyloid formation involves interconverting species with severe consequences such as neurodegeneration and the prion-like effect. We are interested in studying different amyloidogenic proteins involved with neurodegenerative disorders and cancer, the process in which they assemble, the early stages of amyloid conversion, their structure and polymorphism, and how these macromolecular complexes and precursors become toxic to cells.
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The tumor suppressor p53 undergoes mutations leading to oncogenic activities in cancer. We are interested in studying conditions where the p53 phase separates, forming liquid droplet, gel-like, and solid-like amyloid species. By investigating the higher-order p53 oligomeric species, we aim to understand how hotspot p53 mutations develop gain-of-function activities in cancer.