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
Research Topic 3 – Cancer Toxicology
Our group has intensely focused on exploring epigenetic toxicity of Per- and polyfluoroalkyl substances (PFAS). Along with a team at UIUC we are exploring the effect of PFAS on the liver, kidney, and intestine. We have identified a set of genes and epigenetic targets triggered by PFAS toxicity. We utilize single cell techniques, molecular biology tools along with sequencing and metabolomic analysis to assess the toxicity. Specific projects in this area are: (1) Evaluating the effect of co-culture systems on PFAS toxicity, (2) Development of gene editing tools for toxicity reversal; (3) Assessment of Microbiome-epigenome interaction due to PFAS toxicity. We collaborate with Cancer biologists to develop generalized assessment platforms for toxicity evaluation. We work very closely with the Illinois-EPA on PFAS quantification in aquatics and soil samples. In addition we are also exploring avenues to assess PFAS levels in firefighters in collaboration with the Illinois Fire Service Institute. Our group is also involved in multidisciplinary efforts to assess the environmental effects and cancer toxicology of PFAS on a grandeur scale and its effect on local communities in Illinois. Details of this effort can be found at: isrc.illinois.edu
Research Topic 4 – 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.