|Enilza Maria Espreafico
Tel.: (16) 3315-3348
ROLE OF MYOSIN-VA AND ITS LIGHT CHAIN DLC2 IN CELL MIGRATION AND APOPTOSIS.
One of the current aims of our laboratory is to establish the role of myosins-V in the cascade of invasion and metastasis in melanomas and carcinomas. At the moment, we are characterizing the effect of siRNAs against myosin-Va and its light chain DLC2 in tumor cell lineages, as well as the anti-tumor action mechanisms, properties, and efficacy of an apoptosis-inducing peptide derived from myosin-Va. We employ multiple approaches, including the construction of recombinant DNA, transfection and lentiviral transduction of mammalian cells, RNAi silencing, fluorescence confocal microscopy and electron microscopy, polyclonal antibodies production, and protein-protein interaction assays.
IDENTIFICATION AND CHARACTERIZATION OF NOVEL GENES INVOLVED IN MELANOMA PROGRESSION.
Tumor progression is characterized by the acquisition of multiple genetic alterations. Detecting these alterations is mandatory for the identification of new therapeutic targets and the development of targeted therapeutic strategies, so that higher efficiency and specificity are obtained in the battle against cancer. Our projects aim at the identification and functional characterization of novel genes involved in tumorigenesis and metastasis. To this end, we employ melanoma cell lineages at different stages of tumor progression as experimental models, by means of a multidisciplinary approach combining methodologies from the areas of Molecular Biology, Bioinformatics, Biochemistry, and Cell Biology.
GRISCELLI SYNDROME: MOLECULAR DIAGNOSIS AND FUNCTIONAL STUDIES.
The Griscelli Syndrome comprises three subtypes of hereditary diseases, namely GS1, GS2, and GS3, involving the genes MYO5A, RAB27A, and MLPH. These diseases are characterized by alterations in pigmentation and may occur concomitantly with neurological deficiency (GS1), fatal immunodeficiency (GS2), or hypopigmentation alone (GS3). Defective release of lytic granules in T-cytotoxic cells and natural killer accounts for the immunodeficiency associated with the Griscelli Syndrome and other types of primary hereditary immunodeficiency whose main manifestation is the hemophagocytic syndrome, a threatening condition of sudden appearance that may lead to death if left untreated. The only possible cure for this condition is bone marrow transplant. Our research has contributed to works from the clinical area by aiding cell and molecular diagnosis, thereby determining cell alterations and mutations associated with the Griscelli Syndrome. We intend to extend analysis to other hemophagocytic syndromes and develop treatment strategies based on genic (demonstrated by our group at the cellular level in cytotoxic T lymphocytes) or protein therapy. We are also interested in studying the molecular mechanisms involved in cytoskeleton polarization and lytic granules exocytosis during cytotoxic response.