Prof. Dr. Maria Ines VACCARO, PhD, AGAF
PhD in Biochemistry by the University of Buenos Aires, Argentina.
Fellow by the American Gastroenterological Association Institute, USA (AGAF)
Magister in Medical Education by the National University of Tucuman, Argentina.
Full Professor of Pathophysiology by University of Buenos Aires, Argentina.
Senior Researcher by the National Council for Scientific Research, Argentina.
Director of the Institute for Biochemistry and Molecular Medicine, National Council for Scientific Research and University of Buenos Aires.
Research Leader of the Translational Medicine Unit at the Center for Medical Education and Clinical Research UMT-CEMIC, Buenos Aires.
International Council Member of the Autophagy, Inflammation, and Metabolism Center of Biomedical Research Excellence of NIH, USA.
The study of the molecular mechanisms that human cells trigger in response to disease is a very active area of scientific research in medicine. Our work is focused on the molecular mechanisms involved in the early events that occur in pancreatic cells during disease. In the search for new molecules that are differently expressed during acute pancreatitis, we characterized a novel transmembrane protein called Vacuole Membrane Protein 1 (VMP1) that is highly expressed early during the disease. In our laboratory, we discovered that VMP1 triggers autophagy in mammalian cells. Autophagy is a highly preserved process in evolution whereby the cell degrades cytoplasmic components including organelles. Autophagy has been linked to a variety of pathological processes such as neurodegenerative diseases and tumorigenesis, which highlights its medical importance. We demonstrate that VMP1 mediates a new type of selective autophagy (Zymophagy) that acts as a defense mechanism in pancreatic cells. We also demonstrated that VMP1 participates in the mechanisms of resistance to death of pancreatic tumor cells and it is induced by hypoxia and chemotherapy. We showed that the interaction of VMP1 with specific plasma membrane proteins marks a new initiation site for autophagy and that the interaction of VMP1 with BH3 Domain of Beclin1 is required for mammalian autophagy. We recently found that VMP1 is unconventionally secreted by a mechanism under study called secretory autophagy and is found in human serum in the extracellular vesicle fraction (EV). EV are heterogeneous vesicles that are surrounded by the lipid bilayer membrane and are released from the cells into the extracellular environment. EV serve as central carriers of genetic information, regulatory proteins and lipids between cells. In cancer, they mediate intercellular communication between tumor and tumor stroma and support local and systemic effects such as immunosuppression, angiogenesis and formation of a pre-metastatic niche. My present objectives are to characterize the function of VMP1 and its partners in selective autophagy and in the secretion of extracellular vesicles; and to study the relevance of VMP1 secretion as a cellular response to pathologies such as digestive cancers, pancreatitis and diabetes. I consider that the study of the molecular mechanisms that cells are able to activate in the face of complex diseases will allow the developing of new and more rational diagnostic and therapeutic strategies.
Main Research Focus
The aim of my research is the identification and characterization of key pathophysiological processes involved in complex diseases of the digestive tract. The current topics are autophagy, selective autophagy and the noncanonical secretory autophagy in extracellular vesicles secretion, their molecular mechanisms and roles in the cellular response to gastrointestinal, pancreatic and hepatic complex diseases.