- Research Grants
Full Professor of the Institute of Biosciences at the University of São Paulo and Senior Researcher at CNPq. Member of the Academies of Sciences of the State of São Paulo (ACIESP, 1980) and Brazilian (ABC, 2012). Graduated in Biomedical Sciences from Escola Paulista de Medicina (1970) and Ph.D. in Pharmacology from the same institution in 1974. Full Professor in Pharmacology from USP (1989). Since the beginning of her career, she has been active in Scientific Societies and has been President of SBFTE (Brazilian Society of Experimental Pharmacology and Therapeutics) and member of FESBE and SBPC Board of Directors as General Secretary and Treasurer. She served on Advisory Committees of CAPES and CNPq and was a member of the Secretariat for Research and Development Policies and Programs of MCTI (2003) and the National Council for Ethics in Research in Laboratory Animals. She is currently a member of the CNPq Deliberative Council, the SBPC, the Institute of Advanced Studies of USP and the Evaluation Committee of EMBRAPII. Since 2007 he has served as Vice-President of the Friends Association of the Weizmann Institute, Brazil. She is a reviewer for several international journals and belongs to the Editorial Board of the Journal Pineal Research, Frontiers in Cellular Endocrinology and Brain Behavior and Immunity. She co-chaired the 3rd SCR FASEB on Melatonin Biology, Clinics and Therapeutics (2013, Niagara Falls, USA) and is a member of the International Union for Pharmacology Committee (IUPHAR) for melatonin receptors. Research line: He works in the field of Chronopharmacology with emphasis on the role of melatonin on the inflammatory response and cancer. He consolidated knowledge of the area by proposing the Pineal-Immune Axis, responsible for the alternation between melatonin production by pineal or immunocompetent cells. Currently, it is developing new molecular platforms of selective and mixed ligands of melatonin receptors, delivering cancer therapies, overweight and neurodegenerative diseases based on the concept of the Pine-Immune Axis, proposed by the group led by Regina P Markus. In 2018, this axis was considered as an organizing system between the effects of melatonin as a chronobiotic agent and modulator of the immune system in Brit's editorial. J. Pharmacol. Next, work begins to emerge from different groups that cite the process of controlling the pineal and extra-pineal production of melatonin, as regulated by the pineal-immune axis. The search for theory to organize the knowledge of melatonin as a chronobiotic agent and an immunomodulatory agent and the different sources of melatonin synthesis allowed the creation of a gene index that relates synthesis enzymes and degradation to estimate the capacity of a fabric synthesize melatonin. These data, applied to different tumors, can be used as a prognostic index of evolution. In collaboration with researchers at the Weizmann Institute for Research in Israel in 2018, he proposes that the bone marrow of mice can rhythmically synthesize melatonin under the direct command of the sympathetic nervous system and coupled to an endogenous rate of TNF. These are unpublished findings that will promote a paradigm shift in the understanding of the physiology of the formation of blood and bone cells, and also in spinal dysfunctions. More recently, considering the advances that the group has made in understanding the purinergic control of melatonin production, the hypothesis has been successfully evaluated that against high concentrations of external ATP, which may be due to cell death in the vicinity of the pineal gland, the precursor of melatonin (N-acetylserotonin) becomes the dark hormone. (Source: Lattes Curriculum)
|News published in Agência FAPESP Newsletter about the researcher|
|Melatonin may help boost the success of bone marrow transplants|
|Melatonin levels can be used as an indicator of tumor malignity|
The pineal gland is a unique structure of ectodermal origin, whose hormone melatonin, is also known as dark hormone, because it tells the internal environment the duration of the night. This gland is also integrated with the body's defense processes, since it negatively regulates the migration of leukocytes to peripheral tissues and the production of pro-inflammatory agents by several c...
Our collaborative project aims at understanding how light/dark dependent signals regulate physiologic immune-cell generation and host-defense as part of homeostasis and in response to inflammatory insult. Identificating regulatory mechanisms and key molecules will provide new targets for improving clinical procedures such as stem cell transplantation and immunotherapy. (AU)
The equipment is a confocal/facs allowing the separation of cells and the simultaneous evaluation of molecular markers and cell structures. In the project AMNIS will allow the analysis of phenotypic changes, gene expression, cell interaction, receptor expression and transduction pathways definition. In our project our goal is to understand the mechanisms involved in the activation and...
The Immune-Pineal Axis hypothesis provides the molecular basis for understanding the role of melatonin in the surveillance for external aggressions and internal disorganization of the [39, 97, 98]. In addition, it explains how the production of melatonin is shifted from the pineal gland to peripheral immune cells and microglias during an innate immune response. The goal of the present p...
(Only some records are available in English at this moment)
Our goal is to provide proofs of concept that the production of melatonin by cancer cells of the urinary bladder and intestinal colon is a factor that reduces proliferation through the stimulation of melatonin receptors located in the tumor cell itself. The effect of each of the melatonin receptor subtypes through selective melatonin receptor agonists or mixed characteristics (agonist /...
The pineal gland regulates several biological rhythms and defense responses in healthy subjects by producing melatonin at nighttime. On the other hand, inflammatory mediators impair pineal melatonin synthesis. Our preliminary data presented in this project highlights that low-grade inflammation generated by diet-induced obesity model inhibits nocturnal melatonin synthesis at night and b...
Heparan sulfate is a glycosaminoglycan of the extracellular matrix that is bound to a proteoglycan. When occur a disruption of matrix there is a formation of free disaccharides that could bind to toll-like receptors and trigger inflammatory responses. Knowing that the suppression of nocturnal melatonin production in the pineal gland is induced by molecular patterns associated to bacteri...
Gliomas are recurrent primary brain tumors classified according its proliferation rate and invasiveness. A preliminary study of gene expression in material obtained from patients with glioma showed a significant negative correlation between the grade of invasiveness and the expression of the gene that encodes the enzyme responsible for converting N-acetylserotonin (NAS) in melatonin (ME...
(Only some records are available in English at this moment)
During the mounting of inflammatory responses, the bidirectional communication between the pineal gland and the immune system induces the suppression of melatonin production in the pineal to allow the proper migration of macrophages and the initiation of the non-rhythmic production of melatonin in the site where the inflammatory process is occurring. We have shown that the TLR4 plays a...
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
|Data from Web of Science|
(References retrieved automatically from State of São Paulo Research Institutions)
MACHADO, Sanseray da Silveira Cruz. Caracterização dos receptores tipo Toll em glândulas pineais de rato e sua implicação no entendimento do eixo imune-pineal. 2015. Tese (Doutorado) – Instituto de Biociências. Universidade de São Paulo (USP). São Paulo.
FRANCO, Daiane Gil. Efeito da melatonina sobre a viabilidade de células granulares de cerebelo em cultura depende do contexto celular. 2014. Tese (Doutorado) – Instituto de Biociências. Universidade de São Paulo (USP). São Paulo.
CECON, Erika. Sistema melatonérgico como alvo do peptídeo beta-amiloide. 2014. Tese (Doutorado) – Instituto de Biociências. Universidade de São Paulo (USP). São Paulo.
MORAES, Renato Couto. Papel da corticosterona na vigência do estresse sobre a função pineal em ratos.. 2010. Tese (Doutorado) – Instituto de Ciências Biomédicas. Universidade de São Paulo (USP). São Paulo.
TAMURA, Eduardo Koji. Efeito da melatonina sobre a produção endotelial de óxido nítrico in vitro e in vivo. 2009. Tese (Doutorado) – Instituto de Biociências. Universidade de São Paulo (USP). São Paulo.
FRANCO, Daiane Gil. Modulação da produção de óxido nítrico por melatonina em cultura de células de cerebelo. 2010. Dissertação (Mestrado) - Instituto de Biociências. Universidade de São Paulo (USP). São Paulo.
MACHADO, Sanseray da Silveira Cruz. Caracterização do eixo imune-pineal: glândula pineal como alvo para lipopolissacarídeo (LPS). 2010. Dissertação (Mestrado) - Instituto de Biociências. Universidade de São Paulo (USP). São Paulo.
SOUSA, Cláudia Emanuele Carvalho de. Caracterização do eixo imune-pineal: mecanismo de ação do controle da função pineal pela citocina pró-inflamatória TNF. 2011. Dissertação (Mestrado) - Instituto de Biociências. Universidade de São Paulo (USP). São Paulo.
SOUSA, Cláudia Emanuele Carvalho de. Efeito da poluição atmosférica de São Paulo sobre o Eixo Imune-Pineal. 2015. Tese (Doutorado) – Instituto de Biociências. Universidade de São Paulo (USP). São Paulo.
FERNANDES, Pedro Augusto Carlos Magno. Regulação da produção hormonal da glândula pineal de ratos por moduladores do processo inflamatório. 2009. Tese (Doutorado) – Instituto de Biociências. Universidade de São Paulo (USP). São Paulo.
CECON, Erika. Fator de transcrição NFKB em glândulas pineais de ratos. 2010. Dissertação (Mestrado) - Instituto de Biociências. Universidade de São Paulo (USP). São Paulo.
FREITAS, Marina Marçola Pereira de. Efeito da melatonina endógena sobre a reatividade de células endoteliais ex vivo. 2011. Dissertação (Mestrado) - Instituto de Biociências. Universidade de São Paulo (USP). São Paulo.
LIMA, Kelly Dhayane Abrantes. Modulação da interação neutrófilo-endotélio in vitro por melatonina: ação sobre as células endoteliais. 2011. Dissertação (Mestrado) - Instituto de Biociências. Universidade de São Paulo (USP). São Paulo.