The solutions to the most pressing problems in healthcare today - ranging from Alzheimer’s disease, cancer and diabetes – will require novel capabilities to accurately measure biological systems at the molecular level. Dr. Hariri will combine expertise in molecular design and optics to engineer novel single molecule tools and transformative platforms for monitoring and diagnostics to help unravel some of the grand challenges of biomedical research. Dr. Hariri's group will pursue the following three research areas:
Area #1 Integrated Biosensors: Unravelling the spatial and temporal dynamics of neurochemicals in the brain.
Ongoing research aimed at developing new therapies for a variety of brain disorders including Parkinson’s disease, Epilepsy, and Alzheimer’s disease, depend on our ability to monitor neurochemicals such as neurotransmitters in the brain. Neuroscientists have clearly established that a variety of chemical species/processes act together over multiple temporal and spatial domains to govern a specific behavior. However, so far, no technology allows the detailed mapping of the spatially and temporally dynamic chemical content of the brain with a sufficient resolution across different regions. Addressing these challenges will be at the heart of my group’s research goals. The research goal of my lab will be to create materials and tools that will allow a quantitative chemical view of the brain across scales from single neuron to brain slice to the living brain. Importantly, we will be focusing on: 1) Building an integrated optical biosensor that can detect “in real-time” physiological concentrations of neurochemicals in-vivo in order to achieve higher temporal resolution measurements for investigation of biological processes and behavioral events. This will enable the mapping of multiple neurochemicals at finer scales and with better precision; 2) creating minimally invasive approaches to reduce artifacts or perturbations of biological systems caused by the measurement device; 3) developing material chemistry approaches to address biofouling and biocompatibility problems. Finally, we will expand the use of this optical biosensor platform to detect pathogens, proteins, and many biomarkers to provides valuable information about a given disease state such as Diabetes and Cancer.
Area #2 Novel diagnostic mechanisms: Ultrasensitive sensor platforms for low abundance molecular detection.
Early detection is the most effective means of improving prognosis for many diseases such as cancer. A major requirement for early-stage diagnosis is the provision of assays that can be at the same time sensitive and specific for individual biomarker, and in most cases capable of quantifying multiple biomarkers at the same time. The current gold-standard in the field of biomolecular detection is the enzyme-linked immunosorbent assay or ELISA. However, conventional ELISA-based diagnostic assays suffer from various limitations. For instance, in many cases such as early disease diagnostics, the concentration of targets is too low to be detected, and their sensitivity is fundamentally limited by the noise in an assay. In my group, we want to develop proteomics assays by integrating advanced proofreading steps to provide the necessary combination of sensitivity and specificity for important biomarkers. Specifically, we want to interface sandwich immunoassays with the DNA self-assembly toolbox and use cutting-edge single molecule methodologies as a readout modality. The success of this approach will enable routine detection of sub-femtomolar concentrations of biomarkers in clinical samples.
Area #3 Aptamer switches for multifunctional stimulus-responsive Nano-systems
Aptamer switches designs range from molecular beacons or strand displacement-based sensors that generate a fluorescent readout in response to ligand binding, to much more sophisticated constructs that can be externally manipulated through the targeted application of light, or by exposure to specific chemical or microenvironmental conditions. Many of these devices have proven capable of executing relatively complex functions, including drug delivery vehicles for the targeted and controlled release of therapeutics, or molecular sensors. Beyond the basic switching mechanisms developed previously, my group is interested in building more sophisticated nucleic acid-based systems by integrating DNA bricks, tiles, or origami design principles with aptamer switches to perform complex functions and execute specific mechanistic responses to biochemical triggers with specific temporal/spatial control, including targeted therapeutic activity in vivo.