Cell Biology (actin cytoskeleton, cell signaling, vesicular transport) and Immunology (inflammation, COX-2 and Prostaglandin E2 production, subpopulations of T lymphocytes, Treg cells, cytokines) of Protozoan parasites (mainly Entamoeba histolytica and Leishmania mexicana). More recent research on ovarian cancer (OvCa) looking for biomarkers and studying mechanisms involved in the disease development.
Initial contact between the trophozoites membrane and host cells is an important event that precedes the host cell lysis. There is plenty of evidence suggesting that the cytoskeleton and lectin activities may participate in this process. The properties of the membrane and its relation with the cytoskeleton may help the parasite to invade the host tissues as is the case for the liver. In this process, the trophozoite needs to recognize and interact with extracellular matrix components such a fibronectin (FN), in order to degrade them and reach the target organs. My group is interested in the signaling processes that occur during the interaction of trophozoites with FN. Particularly, on the effect that such signaling exerts on the actin cytoskeleton structuration, and on the exo- and endocytosis processes of the FN receptor; all these aspects we are studying them using diverse methodological strategies and methodologies. Right now, we are studying:
§ If the interaction with FN induce the expression of different actin isoforms.
§ The participation of different GTPases in the actin polymerization process and the effect of diverse drugs on the actin structures.
§ The participation of Rab proteins (mainly Rab 21 and Rab 11) during the exo- and endocytosis of the FN receptor and during erythrophagocytosis.
§ Induction of COX-2 activity as a result of FN interaction.
§ Proteomic analysis of associated components during the formation of different actin structures.
All these projects with the aim to understand the mechanisms involved in the pathogenicity of this parasite, which until now is considered as a primitive eukaryote.
Cutaneous leishmaniasis is produced by L. mexicana; it presents three clinical manifestations: localized, difuse and predifuse. It is not clear whether these manifestations are due to the host, to the parasite or to the combination of both. We have studied the humoral and cellular immune responses, induced in two different mice strains; one that is naturally resistant (C57/BL), and one that is susceptible (BALB/c) to the infection by L. mexicana. We have established that in the mice model, PGE2 inhibits the production of Interleukin 12 (IL-12) in the susceptible model during the initial phase of the immune response, thus driving the immune response towards a predominance of the Th2 subpopulation. More recently we have identified that macrophages are one important source of PGE2, through the induction of COX-2 enzyme; also we have described the signaling pathway involved in this COX-2 activation.
Moreover, we have also found that there is a COX-2 like activity in Leishmania mexicana and we are analyzing the possible role of this enzymatic activity of the parasite in the modulation of the host immune response.
Ovarian Cancer (OvCa).
Ovarian cancer (OvCa), among the gynecological cancers, occupies the main place as the cause of mortality in Mexico. It presents with very unspecific symptoms, and this is the reason why both women and physicians attribute the clinical manifestations to other common conditions. And then, it is too late when they discover the metastasis of the tumoral cells towards the abdominal cavity that induces the production of malignant ascites, unequivocal sign that the cancer has disseminated. In our laboratory we are interested in monitoring the changes in the expression profiles of proteins that constitute the ascites fluid and that could have important roles as biomarkers to follow the course of clinical manifestations, and also with the aim to understand better the molecular mechanisms that determine the growth and the tumor progression. Eventually we would like to define molecules for the design of new diagnostic methods able to detect early phases of OvCa.