Gupta Laboratory

General Information

Research Interests

• High-throughput screening based drug discovery. Investigating the mechanism(s) of integrin activation (both structural as well as signaling), development of methods and tools for perturbing the process of cell adhesion and to determine its functional consequences in vivo in various types of inflammation.
• Proteomic profiling and data mining based approaches to model the cellular interactome to identify protein hubs regulating cell adhesion and their role in human disease.

Keywords and Phrases

• HTS (high-throughput screening
• Integrin activation
• integrin signaling
• Modulating function of integrins using small molecules
• Role of integrin in inflammation in vivo
• Platelet biology
• Leukocyte biology

Contact Information

• Office location: Batchelor Bldg., 6th Fl, Room 633 (R-762)
  1580 NW 10th Avenue
  Miami, FL 33136
• Phone: (305) 243-2302
• Fax: (305) 243-4338
• Lab Location: Batchelor Bldg. 6th Fl
  1580 NW 10th Avenue
  Miami, FL 33136
• Tel: (305) 243-4176
• Fax: (305)243-4338
• E-mail: VGupta2@med.miami.edu

Members

Research

The Gupta laboratory works at the interface of chemistry and biology. We develop and apply novel chemical and systems biology tools to obtain a better understanding of the process of inflammation and mechanisms of resolving inflammation. Our research focuses on cellular receptors called integrins and integrin-based cell adhesion. This includes investigations into the mechanism(s) of integrin activation (both structural as well as signaling), discovering novel drug-like small molecules that modulate integrin function, determining the functional consequences of modulating integrin activation in vivo, and proteomic metabolomic profiling as well as data mining based approaches to model the cellular interactome to identify protein hubs regulating cell adhesion and their role in human disease.

• High-throughput Screening
  We are carrying out high-throughput screening of small molecule libraries to identify small molecules that modulate the biological function of beta2 integrins (CD11a/CD18, CD11b/CD18). 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 by allosterically inducing conformational changes in the three dimensional structure of integrins. We have developed novel assays for such HTS screens and we have discovered a number of novel agonists and antagonists of the beta2 integrins and further characterization is currently underway.
• Understanding the mechanism of Integrin Activation using Chemical Biology Tools
  One major project involves applying chemical biology tools to study the mechanism of integrin activation. This includes determining structure-function relationships using site-directed mutagenesis and functional analyses using mammalian cell culture.
• High-content Proteomics
  We are collaborating in the area of high-content proteomics with the Harvard Partners Center for Genetics and Genomics to determine proteomic signatures of human sera, urine and purified platelets. The diseases we are studying include Chronic Kidney Disease and Type I Diabetic Nephropathy. Goal is to develop a comprehensive profile of these specimens. In collaboration with Dr. Zaki, Professor of Computer Science and Bioinformatics at RPI, we are performing extensive modeling of the generated proteomics data to obtain the human interactome for each of the systems under study. A particular focus of the proteomic and metabolomic profiling studies is to identify novel early markers of diabetic nephropathy and of chronic kidney disease in patients.

Selected Publications

• Gupta*, V., Alonso* J.-L., Sugimori T., Issafi M., Xiong J.-P. and Arnaout M. A., Role of the beta-subunit arginine/lysine finger in integrin heterodimer formation and function, Journal of Immunology, Feb 2008.
• Wei C., Möller C.C., Altintas M.M., Li J., Schwarz K., Zacchigna S., Xie L., Henger A., Schmid H., Rastaldi M.P., Cowan P., Kretzler M., Parrilla R., Bendayan M., Gupta V., Nikolic B., Kalluri R., Carmeliet P., Mundel P. and Reiser J., Modification of kidney barrier function by the urokinase receptor, Nature Medicine, 2007, AOP Dec 16.
• Park J.Y., Arnaout M.A. and Gupta V., A simple, no-wash cell-adhesion based high throughput assay for the discovery of small molecule regulators of the integrin CD11b/CD18, Journal of Biomolecular Screening,  2007, April; 12: 406-417.
•   Gupta V., Gylling A., Alonso J.-L., Sugimori T., Ianakiev P., Xiong J.-P. and Arnaout M. A. ,The β-tail domain (βTD) regulates physiologic ligand binding to integrin CD11b/CD18, Blood 2007, Apr 15;109(8):3513-20. Epub 2006 Dec 14.
• Gupta V., Cherkassky A., Chatis P., Joseph R., Johnson A. J., Erickson T. and Dimeo J., Directly labeled mRNA produces highly precise and unbiased differential gene expression data, Nucleic Acids Research, 2003, 31, e13.
• Nagata T., Gupta V., Sorce D., Kim W-Y., Sâli A., Chait B. T., Shigesada K., Ito Y. and Werner M. H., Immunoglobulin-motif DNA recognition and heterodimerization for the PEBP2/CBF Runt-domain, Nature Structural Biology, 1999, 615-619.
• Goger M., Gupta V., Kim W-Y., Shigesada K., Ito Y. and Werner M. H. ,Molecular insights into PEBP2/CBF-SMMHC associated acute leukemias revealed from the three-dimensional structure of PEBP2/CBF beta, Nature Structural Biology, 1999, 620-623.
• Gupta V., Parthasarathsy S. and Zaki M. J., Arithmetic and Logic Operations with DNA, Proceedings of the 3rd DIMACS Workshop on DNA Based Computers 1997, 212-220.