Projects
Regulation of cellular metabolism in immune cells
Recently we are focusing our efforts on understanding how the cellular metabolism drives the cell fate. Cellular metabolism is considered as new level of regulation over the cell development, phenotype, and function. Glycolysis, beta-oxidation, glutaminolysis, and oxidative phosphorylation, for instance, are sources of energy, and each cell type has its preferential metabolic pathway to perform a particular function at a particular time. Moreover, changes in mitochondrial shaping or communication with other organelles as well as the use of drugs that inhibit or favor one metabolic pathway over the other offer potential targets to modulate the immune response. The control of metabolic pathways is mediated by molecules referred as “metabolic sensors” (e.g., AMPK, mTOR, HIF-1α, sirtuins, among others), which the members can crosstalk with several other fundamental signaling pathways, generating multiple and exciting opportunities to be explored. Our daily routine uses different inflammation models (e.g., kidney diseases, intestinal diseases, obesity, among others) well established in both mouse and zebrafish, aiming to increasingly fill the gap between basic science and clinic.
Inflammation and acute and chronic kidney injuries
As stated earlier, we investigate several types of inflammatory responses in several organs. However, we have a strong basis on kidney diseases. Considered today an epidemic, they have high social and economic impact with increasing rates in patients’ morbidity and mortality. Both innate and adaptive immune responses play a central role in the pathophysiology of both acute and chronic kidney injuries as well as in the process of fibrogenesis. Because of the growing discoveries of specific cell markers, new active molecules and extra functions for molecules already described, different approaches have been taken to modulate kidney-infiltrating and kidney-resident immune cells. Thus, we hypothesized that kidney offers unique environments that can influence inflammatory response. Therefore, we investigate the role of several immune cell subsets (e.g., B and T lymphocytes, neutrophils, macrophages, dendritic cells, NKT cells, among others) and their activation signaling pathways (e.g., Toll-like. Nod-like, and inflammasome receptors) considering their environmental pressure to perform our in vitro and in vivo experiments. Finally, we believe that the modulation of immune response using different therapeutic strategies, pharmacological or not, can influence the phenotype and function of both non-immune and immune-infiltrating kidney cells in favor of a better functional outcome for the organ.
Stem cells and kidney regeneration
Hematopoietic and mesenchymal stem cells are cells with sufficient plasticity to regenerate tissues and restore physiological functions in damaged organs. Therefore, we have investigated mechanisms and the potential use of these cells in organ transplant and acute kidney injury models, their plasticity in differentiating into tubular cells, and the bidirectional relationship with the immune system.
Microbiota, obesity, short-chain fatty acids, and inflammation
Several national and international research groups, including ours, have consistently shown the role of agents (e.g., microbiota) or biological products (e.g., short-chain fatty acids – SCFAs) over local or distant inflammatory sites. For example, intestinal microbiota transplantation has been demonstrated good perspectives on the treatment of kidney diseases, obesity, inflammatory bowel diseases and even neurological diseases. Lifestyle, including physical fitness, diet, environment, and so on, changes the quality and the quantity of your body microbiota, which in turn, produces products such as SCFAs, that can prevent the development or progression of infirmities. Thus, we also aim to understand how the crosstalk between the gut and other tissues, as the kidney and the skin, can be used as tool to treat inflammatory diseases in extra-intestinal organs.
Regulatory cells and organ transplantation
The induction of tolerance remains the only strategy to increase graft survival without causing toxic graft damage. CD4+CD25+FoxP3+ T cells, or regulatory T cells, have been well characterized in the last decades and their importance have been described in autoimmune diseases, viral infections, cancer, and organ transplantation. Recently, other mechanisms and regulatory immune cells (e.g., regulatory B cells, myeloid-derived suppressor cells, among other) have been also illuminated. Thus, other the laboratory is also interested in studying tolerance mechanisms, especially during kidney transplantation and inflammatory kidney diseases.
Protective genes: heme oxygenase 1 (HO-1) and kidney
Heme oxygenase 1 (HO-1) is considered a protective gene with anti-apoptotic, anti-proliferative, and anti-inflammatory activities. HO-1 expression is robustly induced after kidney ischemia/reperfusion to limit the extension of kidney lesion and it can also suppress atherosclerotic lesions in experimental models of chronic rejection. However, HO-1 expression may be regulated by a polymorphism in its promoter and after immunosuppressant treatments. Therefore, the laboratory is interested in studying the role and how to modulate the expression of HO-1 in acute kidney injury, kidney transplantation and injury, and in vitro models of epithelia-to-mesenchymal trans differentiation.
Zebrafish disease modeling
Zebrafish (Danio rerio), also known as “paulistinha”, has many advantages as an experimental model. Zebrafish has the interesting feature of performing external fertilization with transparent eggs which, when fertilized, develop rapidly, and can form a complete embryo within 24 hours. The high regenerative capacity of zebrafish from various organs such as the central nervous system, heart, kidneys, and liver, makes the model interesting for studying inflammatory diseases. With respect to zebrafish immune system, it shares mammalian neutrophil-like cells, macrophages, dendritic cells, B and T lymphocytes. The laboratory focuses on the immune response using inflammatory disease models in Zebrafish as a tool to identify new disease mechanisms and actions of potential therapeutic drug candidates.