The transdisciplinary character of i3S is achieved through Integrative Research Programs and by promoting projects addressing questions that require participation of basic and applied sciences, such as:
- The development of effective and reliable in vitrodiagnostic tools, namely for early detection of gastric cancer and bacterial infection, combining molecular targets and nanotechnologies, with particular emphasis on in vivobioimaging;
- The development of carriers, scaffolds and cell isolation, and manipulation technologies for effective cell therapies and tissue engineering strategies in neurological diseases and trauma, particularly for elderly and diabetic patients. The specific etiology of disease in these patients is often neglected but should be translated into the design of appropriate in vitro and in vivo strategies;
- The development of fundamental research to solve basic biological questions continues to be a priority and it lays the groundwork for future advancements; it is also a guiding principle in hiring new researchers.
The Cancer integrative program encompasses research groups working on Cell Division, Cell Cycle, Oncobiology, Pathology, Molecular and Cellular Biology, Cancer Genetics, and Population Genetics and Metabolism, in association with groups working on Bioengineering. This program intends to identify risk factors for cell and tissue transformation, as well as the molecular and cellular mechanisms relevant for cancer development and progression.
The groups incorporate expertise in cell cycle and cell division, a key area to understand the basis for cell transformation, growth and genetic instability. Our knowledge in pathology, molecular genetics, population genetics and genetic diversity plays a key role in furthering the understanding of the role of nuclear and mitochondrial genetic mutations in cancer. It is well known that cancer cells show changes in/loss of differentiation and, in most cases, exhibit an increase/shift in bioenergetic demand when compared to normal cells. Therefore, our groups amass expertise in metabolism, cell signaling and apoptosis, which are important to broaden our understanding on how to restrain cancer growth, to induce cell differentiation and/or to promote cell death. Additionally, we focus on the role of cell junctions, cell-extracellular matrix (ECM), and interactions of other cellular and non-cellular components of the cancer microenvironment to understand tissue architecture, cell adhesion, cell communication, migration and invasion.
We gather people with expertise in the role of adhesion molecules in cancer, such as P- and E-cadherin, that work in close collaboration with researchers working in ECM and inflammation. Since cancer "stem-like" cells possess self-renewal capability and display increased chemo and radio-resistance, their identification and modulation is important for an effective therapy and to control tumor recurrence. We use cancer patient cohorts, in vivo models and dynamic in vitro models allied to high throughput technology, bioinformatics, and state-of-the-art molecular and cellular biology to identify regulatory mechanisms and molecular circuitries, acting to confer advantageous features to pre-neoplastic and neoplastic cell populations.
Host Interaction and Response
The Host Interaction and Response integrative program aims to understand and decipher the complex crosstalk that takes place between the host immune system and foreign bodies, namely pathogens and bioengineered materials. To tackle these complex questions, this program gathers internationally established groups working on pathogenesis, immunity, clinical and population genetics, biomaterials, tissue regeneration and nanomedicine. Identification and characterization of the virulence mechanisms employed by infectious agents, and the analysis of the mechanisms engaged by the host to sense and control pathogens benefit from the expertise of groups working on host-pathogen interactions using a range of model-systems, from bacteria and fungi to parasites, from extracellular to obligate intracellular pathogens, and from cultured human cells to animal models.
We also study factors that affect the susceptibility to infection and the mechanisms of disease induction based on our studies in leishmaniasis, tuberculosis and microbe-induced carcinogenesis. The interaction with experts in nanomedicine and bioengineering translates into innovative preventive and therapeutic strategies against pathogens. We also explore the molecular and cellular processes of the host immune/inflammatory response and cell-cell/matrix-cell interactions to design biofunctionalized matrices and scaffolds tailored to actively deliver drugs, along with bioactive molecules or genes and cells aimed at promoting tissue repair/regeneration.
The groups below are experts in biomaterials, inflammation modulation, tissue engineering, stem cell biology, drug/gene delivery and nanomedicine.
Innovative tissue repair/regeneration therapies are investigated and explored, namely molecular and cell-delivery systems, extracellular matrix bioanalogues, and stem cell recruitment and differentiation factors to design a new generation of biomaterials and implantable devices to help restore organ/tissue function and architecture.
Neurobiology and Neurologic Disorders
The Neurobiology and Neurologic Disorders integrative program involves groups working on neurosciences, genetics, protein structure and regenerative medicine. It focuses on understanding the biology of neurons and glia, the causes for neuronal dysfunction and degeneration, exploring the use of biomaterials in neural regeneration and developing therapeutic strategies to ameliorate neurological conditions. The groups committed to this program enjoy international recognition, specifically on spinal networks and myelination, amyloid neuropathy, movement disorders, lysosome and peroxisome storage disorders, pain, neurourology, addiction, structural biology, axonal regeneration, design of biomaterials to improve nerve regeneration, and animal science. Cross-program interaction and external collaboration, which already took place, are now further encouraged. For instance, the interaction between epithelial cancer biology groups and groups delving into glial cell biology have been exploring the role of cell-to-cell contacts and cell-matrix interactions in the context of epithelial cancer. Additionally, groups working on gastric cancer and biomaterials have designed functionalized nanoparticles to detect and fight H. pyloriinfection. Similarly, work on neuronal repair in spinal cord injuries has benefited from the design of nerve conduits to guide nerve regeneration.