Research Topic 1 – Nanobubble Therapeutics
We are interested in developing oxygen encapsulated oxygen nanobubbles that can be triggered and steered by ultrasound to improve drug localization at a targeted site for on demand release of therapeutics for enhanced therapy. The nanobubbles are size tunable and are fabricated with FDA approved reagents in the size range between 100nm – 1000nm. In addition to ultrasound guided localization, the particles themselves can act as ultrasound contrast agents and can be triggered by ultrasound for programmable release of oxygen and drugs. Our approach is applicable to most hypoxia driven diseases such as Cancer, diabetes, Glaucoma, etc. Specific projects in this area include, Hypoxia mitigation for Cancer treatment, Stem cell therapy, Retinal diseases, and Wound healing. This work will be conducted at the Biomedical Research Center at Carle Hospital and Beckman Institute.
Oxygen Nanobubbles in a Cell
Steering of Oxygen Nanobubbles by ultrasound in the bladder of a tumor bearing mouse
Research Topic 2 – Single molecule super-resolution technologies for mechanism elucidation in live cells
Our group has developed super-resolution (STED) microscopy based fluorescence correlation spectroscopy, lifetime imaging, and FRET techniques to resolve molecular interactions in live cells and zebrafish. We are one of the first groups to demonstrate loci-specific epigenetic editing utilizing CRISPR and Optogenetics utilizing DNMT, MBD, and TET. We have also developed peptide biosensors to target kinase signaling and have resolved live cell phosphorylation kinetics targeting Abl, Src, Syk, Akt, FAK, VEGF, and MAPK with lifetime imaging at single molecule resolution. In collaboration with biochemists/molecular biologists we are also looking at the stoichiometry and binding partners of SMC (Structural Maintenance of Chromosomes) proteins. Our future goals are to further demonstrate epigenetic editing in stem cell differentiation to develop specific phenotypes and to see proteins/enzymes come ON/OFF during the process of epigenetic programming at single CpG resolution. In collaboration with Dr. Dar we are exploring the stochasticity of epigenetic noise and its role in gene expression. This work will be conducted at Carle and the Micro and Nanotechnology Laboratory (MNTL).
Live cell Kinase signaling visualized with peptide biosensors targeting the kinase domain – Fluorescence Lifetime imaging monitors VEGF kinase signaling
Click here for a snapshot of Single Molecule Florescence Research in our lab
Research Topic 3 – Single nanoparticle in cell technologies and biosensors
We are the first group to demonstrative live cell quantification of mRNA utilizing the plasmons properties of gold nanoparticles. We have further expanded this work for single cell epigenetic profiling and sensing of molecular markers in different cellular compartments. In the long-term our goal is to further translate our concepts for multicomponent tissue profiling utilizing gold nanoparticle probes, quantum/carbon dots at single molecule/particle resolution. This work will be conducted at the Laboratory in Carle Hospital and Beckman Institute.
Live Cell quantification of mRNA – Gold nanoparticle probes target splice junction of BRCA1 mRNA to form dimers (bright spots) – Nature Nanotechnology (2014)
Research Topic 4 – Microbiome Toxicology
In collaboration with the focus group on Microbiome Metabolism Engineering (MME) at IGB we are developing tools – in vitro models to mimic gut and single cell tools to understand the toxicology of the gut and how contaminants are transported, processed, and metabolized. A team at UIUC is exploring various aspects of gut micro biome toxicology. Our goals are to develop 3D in vitro models to mimic the human gut and translation of our optogenetic and single cell mapping tools to understand the mechanism of toxicity and how this affects the immune response.