Escola Paulista de Medicina
Postgraduate Program in Pharmacology

Research Focus

CELLULAR AND MOLECULAR PHARMACOLOGY AND PHYSIOLOGY

CELLULAR AND MOLECULAR PHARMACOLOGY AND PHYSIOLOGY

Research Projects

Multiple processes in different tissues and organs are coordinated by a communication network between cells for the perfect functioning of the organism. This cell signaling occurs through a wide variety of extracellular molecules, including amino acid derivatives, proteins, nucleotides, steroids, fatty acid derivatives, among others, which must be decoded and interpreted by the target cells, generating responses that are fundamental for proper cell function or even for cell and organism survival. The cell responds to a specific signaling molecule (ligand) through interaction with protein macromolecules (receptors, ion channels, enzymes and transporters) leading to the activation of intracellular signaling pathways and the consequent cellular response. Furthermore, it can also lead to the activation of transcription factors and alteration in gene expression. The studies of all these steps are fundamental both for a better understanding of the biology of different organs/systems and of pathological processes. Some of these have been studied by the Program's advisors, such as: gastrointestinal dysfunction associated with muscular dystrophy, neurodegenerative diseases, metabolic diseases, inflammatory processes, infertility and cancer. Drugs can alter the various stages of processing this information and result in the modification of cell function, can benefit the patient and are also being studied. Studies of pharmacokinetics, mechanisms of action, interaction and side/adverse effects of drugs are extremely important and applicable. The discovery of new drugs or molecules and immunotherapeutics for the treatment of different pathological processes depends on molecular characterization, pre-clinical studies and well-designed clinical trials for patients characterized and selected as to their molecular profile and staging. To this end, basic, translational and clinical multidisciplinary studies in different areas of knowledge are important for the development of scientific research within the scope of the PPG in Pharmacology at UNIFESP and the training of highly qualified human resources, the main objectives of this line of research.

CARDIOVASCULAR AND RENAL PHYSIOLOGY AND PHARMACOLOGY

CARDIOVASCULAR AND RENAL PHYSIOLOGY AND PHARMACOLOGY

Research Projects

We have used experimental models in rodents that simulate pathophysiological conditions in humans in order to investigate the mechanisms underlying cardiovascular and renal changes that occur in conditions such as renovascular arterial hypertension, myocardial infarction, diabetes mellitus, obesity, genetic hypertension, renal failure, apnea obstructive sleep, among other pathophysiological conditions. Our objective, in this line of research, is to advance the understanding of the physiological mechanisms of cardiovascular and renal regulation and their importance in conditions in which these mechanisms generate disorder, such as the pathophysiological conditions reported above. Approaches ranging from the investigation of cellular mechanisms, from the organ to the systems and even in the individual as a whole, associating, for example, molecular and cellular, electrophysiological, telemetric, hemodynamic, among others, in a translational and multidisciplinary study have brought together Researchers and Advisors the graduate program in Pharmacology, its students and post-docs, in addition to allowing interaction with other research groups, in Brazil and abroad. The investigation of hormonal, paracrine and autocrine signaling, of complex mechanisms such as, for example, the renin-angiotensin-aldosterone system and its interactions with the sympathetic autonomic nervous system and its cardiovascular and renal repercussions in various physiological and pathophysiological conditions has been one of the important focuses of this line of research. It is noteworthy that the international insertion of our students has been one of our missions, with the objective of improving their academic-scientific training, allowing greater interaction with researchers from other research institutions on the frontier of knowledge, always seeking excellence in the training of students and in qualified scientific production, that is, that in which students and supervisors participate. Finally, it is important to highlight that there is interaction between the participants of this line of research with the other three lines of the graduate program in Pharmacology at UNIFESP, with transdisciplinary actions and interaction between the Program's research groups.

NEUROPSICPHARMACOLOGY, NEUROPLASTICITY AND AGING

NEUROPSICPHARMACOLOGY, NEUROPLASTICITY AND AGING

Research Projects

This line of research aims to investigate molecular, pharmacological, physiological, behavioral and neurobiological aspects of neurodegenerative and psychiatric disorders in experimental animal models. With these investigations, it is intended to clarify pathophysiological mechanisms, the involvement with environmental and physiological predisposing factors, and above all, provide elements for possible new preventive and therapeutic approaches to the following pathological conditions: Schizophrenia, Drug abuse, Depression and anxiety disorders, Epilepsy and aging-related neurodegenerative diseases (Parkinson's Disease and Alzheimer's Disease). In this line of research, animal models already well described for these disorders are used, or new models are developed and proposed, such as the strain of spontaneously hypertensive rats (SHR) for the study of schizophrenia, or the chronic administration of reserpine (a vesicular monoamine transporter blocker) as a progressive pharmacological model of Parkinson's Disease. Behavioral analyzes include motor, cognitive and emotional assessments related to these pathological conditions in rodents exposed to specific tasks. Approaches to mechanistic and/or pathophysiological investigation include determining levels of neurotransmitters and neuromodulators; the study of neurodegeneration markers; evaluations of protein expression related to the respective disorders or local pharmacological inactivations in specific brain regions. Genetic tools are also used to study the differentiated expression of proteins among the neuronal groups involved in the studied phenomena. For example, a strain of rats with differentiated expression of fos protein (neuronal activity marker) is used to identify specific neuronal groups involved in the genesis or extinction of the compulsive behavior of the use of ethanol and various psychostimulants. Furthermore, we studied the role of neuroinflammation factors, such as astrocytic and microglial activation and cytokine production, as participants in the pathophysiology of some of these diseases, and possible therapeutic targets. Regarding preventive and therapeutic approaches, we have also been working with the investigation of the effects of innovative treatments for some of these disorders, such as: the use of cannabidiol (a component of Cannabis sativa) for the prevention and treatment of schizophrenia; natural products of diverse origins that potentially delay the development of neurodegenerative diseases; drugs with epidemiological potential for the prevention of neurological disorders, such as caffeine and its relationship with protection against Parkinson's disease. Still from the point of view of therapeutic strategies, we also focus on the use of neural and mesenchymal stem cells in diseases of the central nervous system, such as Alzheimer's disease and epilepsy. This development involves the study of neural protection mechanisms related to both cell therapy and the neuronal degeneration itself present in these pathologies. Finally, in the studies described above, environmental and physiological factors that may change the prevalence or manifestation of disorders are taken into account, such as age, gender, emotional factors, stress, sexual hormonal cycles, factors related to neurodevelopment, profiles genetics that confer resistance to diseases, among others.

NATURAL PRODUCTS, DRUG DEVELOPMENT AND BIOMARKERS

NATURAL PRODUCTS, DRUG DEVELOPMENT AND BIOMARKERS

Research Projects

The first Brazilian initiative in public investment in medicinal plants was the creation of the Medicines Center (Ceme) in 1982 (disbanded in 1991), which implemented a research program of plants for popular use in Brazil, with the objective of obtaining possible substances assets that served for the preparation of new drugs and medicines. In recent years, natural products (from plants and animals) have been regaining space and importance, either through the actions of their active principles or as an inspiring source of new bioactive molecular patterns. In the application of drug planning strategies, studies of the evolutionary processes of molecular recognition in biological systems are of great importance, as they constitute the fundamental basis for understanding properties such as potency, affinity, selectivity and toxicity. Biotechnological tools associated with medicinal chemistry methods gain a prominent role in the development of new molecules with biological activity. The great advances in genomics and proteomics, together with the evolution of X-ray crystallography and nuclear magnetic resonance techniques, provide a significant increase in the number of molecular targets with extremely useful information for the discovery of drugs and new molecules. Since the creation of our PPG Program in Pharmacology, advisors have been carrying out research in the area of ​​natural products and UNIFESP has encouraged the creation of multi-user laboratories with all the technologies mentioned above. Currently, the evaluation of the efficacy and molecular mechanism of action of compounds isolated from medicinal plants with hypotensive/antihypertensive and antacid/antiulcer activities has been explored. In addition, poison toxins, due to their possible use for therapeutic purposes, as drugs and/or as a structural model for drug development, are being explored. Biological markers (biomarkers) are macromolecules present in tissues, blood or other biological fluids, which can be produced by healthy individuals, however, high levels indicate dysregulation and, therefore, the possible presence of a pathological process. There is a huge variety of biomarkers, which can be proteins, including enzymes, cell/nuclear membrane receptors or antibodies; nucleic acids; small peptides; among others. These markers can be useful for patients, aiding the diagnosis processes, disease staging, assessment of therapeutic response, recurrence and prognosis. In addition, they help in the development of new treatment modalities and/or in the evaluation of the pharmacokinetics of drugs. One of the greatest current challenges is the development of target-specific drugs that do not damage normal cells or that can be used in combination with conventional therapies. Biomarker identification is now often performed using techniques such as large-scale sequencing, gene expression arrays and mass spectroscopy to quickly identify individual biomolecules or groups of biomarkers that differ between healthy and pathological samples. UNIFESP has multi-user equipment for “omics” technologies and several laboratories of our Program advisors have been developing molecular and cellular biology, biochemical and in vivo studies techniques using classical techniques of physiology and pharmacology in animals in search of new targets for the indication prevention measures and early detection of diseases such as leukemia, cancer, hemochromatosis, among others. Therefore, this line of research is characterized and intended for the translation of knowledge, with the possibility of advancing in innovation and prospecting for new molecules and of training human resources at the frontier of knowledge.


© 2013 a 2021 - Universidade Federal de São Paulo - Unifesp
Instituto de Farmacologia e Biologia Molecular - Rua Três de Maio, 100 - Vila Clementino, São Paulo - SP - ppg.farmacologia@unifesp.br