Current Projects in the Gupta Laboratory
Discovery of Novel Anti-Inflammatory Drugs via High-throughput Screening
Structural mechanism of Integrin Activation
Our laboratory is focused on leukocyte-specific beta2 integrin family. Beta2 integrins (CD11a/CD18, CD11b/CD18, CD11c/CD18 and CD11d/CD18) are key to the biological function of leukocytes and mediate leukocyte adhesion and migration to the sites of inflammation. We have identified a number of small molecules that modulate the ligand-binding function of beta2 integrins. Detailed in vitro and in vivo characterization of these compounds is currently underway. In addition to being useful as therapeutics, the newly discovered molecules also serve as novel chemical biology probes to study the effects of functional modulation of integrins in vivo and to study the mechanism of integrin activation. We have also developed novel cell-based assays for High Throughput Screening (HTS) of chemical libraries and are using these assays to identify novel compounds.
Figure Legend: 3D ribbon model of integrin CD11b/CD18 (Mac-1, aMb2).
Novel Technologies for Molecular Diagnostics in Resource-Poor Settings
Another focus in the laboratory is towards development of novel assays and techniques for rapid, low-cost detection of infectious agents that are applicable in a low-resource setting. We have developed novel methods for DNA/RNA amplification that would allow for ready, multiplexed detection of multiple species using existing diagnostic systems and technologies and are currently optimizing these assays.
Protein-Protein interaction Networks and Signaling Pathways
In collaboration with Professor Mitsu Ogihara in the Department of Computer Science at University of Miami and with Professor M. J. Zaki, Professor of Computer Science and Bioinformatics at RPI, we are performing extensive modeling of a number of proteomics datasets (including some generated in our lab) to determine protein-protein interaction (PPI) networks in a variety of human cells and to devise new computational approaches for determining biologically relevant modules, dynamic changes in the PPI networks upon changes in cellular state and specific signaling pathways and their components.
Novel DNA-based nanomoters.
In this project area we are investigating applications of unique DNA and RNA sequences for producing novel structures (some self-assembling) and assemblies. We are also attempting to create DNA-templated nanoassembly and other nanomotors. Additionally, we are attempting to generate novel biologicals using the principles of Synthetic Biology.
Figure Legend: Three-dimensional model of a single-stranded DNA circle.