In terms of instrumentation, we are currently developing a research tool to measure O2 partial pressure in vivo that addresses most of the limitations of all existent approaches. This instrument will increase the spatial and temporal resolution of current "state of the art techniques", to eliminate artifacts induced by the measurement, and increase the sensitivity to a few photons. The principle of my approach is cross-correlation-based phase detection of single photon emission from low-energy modulated excitation of porphyrin quenching phosphorescence.
My goal is to increase signal-to-noise ratio at the theoretical limits of signal detection. These precise measurements will define the basis to understand O2 sensing and regulation, beyond mechanisms operating at organelle and molecular level. Oxygen regulation is determined by its fluxes, replacing the stable concentration paradigm. Based on this conceptualization, healthy oxidative phosphorylation reflects physiological O2 fluxes, and metabolic (bioenergetic) disruptions reflect early phenotypic changes and vulnerabilities. A similar approach will be used to develop instrumentation to quantify gaseous ligands, keeping in mind that all instruments should be translatable to be used as clinical diagnostic tools.
The understanding of O2 transport and regulation will define the approach to probe other ligands, including NO, CO and H2S. This research must proceed in parallel, since O2 affects the other gaseous ligands' availability, and NO, CO and H2S regulate O2 utilization. Currently, our research has produced several therapeutic breakthroughs, which are also very powerful research tools, including:
- Development of a fully synthetic ligand carrier capable of delivering O2 to tissues at extreme anemic conditions, a real transfusion alternative. in press Anesthesiology, 2011.
- Development of injectable ligand-releasing nanoparticles that restore NO availability during endothelial dysfunction, hemolytic anemia, malaria, and hemorrhagic shock. Am J Physiol Heart Circ Physiol 49-56, 2011; Free Radical Bio Med 530-8, 2010. Am J Pathol 1306-15, 2010; in press Resuscitation, 2011.
- Modifying the NO releasing nanoparticles platform to transport and deliver H2S.
- Development of injectable vesicles that transport and release CO.
These research tools, new instruments and intravital microscopy have allowed me to study:
- Tissue gaseous ligands sensing, distribution and transport in clinically relevant scenarios.
- The modulation and understanding of cardiovascular functions to gaseous ligands.
- Vascular damage and neurological complications due to parasitic diseases (malaria).
- Hypometabolism, to ensure organism viability in extreme conditions.
As population increases, and healthcare transitions to personalized medicine, understanding the role of atmospheric and environmental changes in biology will promote individualized treatments of diseases and endemic sicknesses. The future of my research relates to areas that include treatment techniques (basic research, diagnosis, and treatment procedures), advanced imaging, medical devices, biomaterials, and bioscience of extreme conditions, such as climate change and outer space adaptation.