Indraneel Ghosh
Professor, BIO5 Institute
Professor, Chemistry and Biochemistry-Sci
Primary Department
Department Affiliations
(520) 621-6331
Work Summary
The broad objective of our research program in Bioorganic Chemistry and Chemical Biology is to construct protein therapeutics, protein mimetics, biomaterials, and biosensors. Our research at the University of Arizona is highly multidisciplinary and utilizes techniques in organic synthesis, biochemistry, molecular biology, and a host of physical characterization methods. Our research motto is simple: Unraveling mysteries and Enabling discoveries.
Research Interest
Professor Neel Ghosh, is the Emily Davis and Homer Weed Distinguished Professor ’08 at the University of Arizona. His laboratory is broadly interested in Chemical Biology and Protein Design and Engineering with a focus on developing new tools and methods for advancing human health. The laboratory has a particular current interest in understanding protein kinases and protein-protein interactions and designing new ways to inhibit them in human diseases. Neel Ghosh is also a co-founder and Chief Scientific Officer for Luceome Biotechnologies. Neel received his doctoral degree in 1998 while working with Professor Jean Chmielewski at Purdue University. His doctoral research focused on designing inhibitors of protein-protein interactions and self-replicating peptides. In 1998 he joined Professor Andrew Hamilton and Professor Lynne Regan’s laboratories at Yale University as a joint postdoctoral fellow. At Yale, he discovered the first conditional split-Green Fluorescent Protein, which has been used as a means for measuring protein-protein interactions by many laboratories and the methodology is sometimes called fluorescent protein complementation. In 2001, Neel Ghosh joined the Department of Chemistry and Biochemistry at the University of Arizona as an Assistant Professor and was promoted to Associate Professor and then to the Davis & Weed Chair and Full Professor in 2011. Keywords: Chemistry, Biochemistry, Biomedical Engineering, Cancer


Bishop, P., Ghosh, I., Jones, C., & Chmielewski, J. (1995). Basic-helix-loop-helix region of tal: Evaluation of structure and DNA affinity. Journal of the American Chemical Society, 117(31), 8283-8284.
Ghosh, I., Stains, C. I., Furman, J. L., Porter, J. R., Rajagopal, S., Li, Y., Wyatt, R. T., & Ghosh, I. -. (2010). A general approach for receptor and antibody-targeted detection of native proteins utilizing split-luciferase reassembly. ACS chemical biology, 5(10).

The direct detection of native proteins in heterogeneous solutions remains a challenging problem. Standard methodologies rely on a separation step to circumvent nonspecific signal generation. We hypothesized that a simple and general method for the detection of native proteins in solution could be achieved through ternary complexation, where the conditional signal generation afforded by split-protein reporters could be married to the specificity afforded by either native receptors or specific antibodies. Toward this goal, we describe a solution phase split-luciferase assay for native protein detection, where we fused fragmented halves of firefly luciferase to separate receptor fragments or single-chain antibodies, allowing for conditional luciferase complementation in the presence of several biologically significant protein targets. To demonstrate the utility of this strategy, we have developed and validated assay platforms for the vascular endothelial growth factor, the gp120 coat protein from HIV-1, and the human epidermal growth factor receptor 2 (HER2), a marker for breast cancer. The specificities of the recognition elements, CD4 and the 17b single-chain antibody, employed in the gp120 sensor allowed us to parse gp120s from different clades. Our rationally designed HER2 sensing platform was capable of discriminating between HER2 expression levels in several tumor cell lines. In addition, luminescence from reassembled luciferase was linear across a panel of cell lines with increasing HER2 expression. We envision that the proof of principle studies presented herein may allow for the potential detection of a broad range of biological analytes utilizing ternary split-protein systems.

Ghosh, I., Stains, C. I., Ooi, A. T., & Segal, D. J. (2006). Direct detection of double-stranded DNA: Molecular methods and applications for DNA diagnostics. Molecular BioSystems, 2(11), 551-560.

PMID: 17216036;Abstract:

Methodologies to detect DNA sequences with high sensitivity and specificity have tremendous potential as molecular diagnostic agents. Most current methods exploit the ability of single-stranded DNA (ssDNA) to base pair with high specificity to a complementary molecule. However, recent advances in robust techniques for recognition of DNA in the major and minor groove have made possible the direct detection of double-stranded DNA (dsDNA), without the need for denaturation, renaturation, or hybridization. This review will describe the progress in adapting polyamides, triplex DNA, and engineered zinc finger DNA-binding proteins as dsDNA diagnostic systems. In particular, the sequence-enabled reassembly (SEER) method, involving the use of custom zinc finger proteins, offers the potential for direct detection of dsDNA in cells, with implications for cell-based diagnostics and therapeutics. © The Royal Society of Chemistry 2006.

Shomin, C. D., Restituyo, E., Cox, K. J., & Ghosh, I. (2011). Selection of cyclic-peptide inhibitors targeting Aurora kinase A: Problems and solutions. Bioorganic and Medicinal Chemistry, 19(22), 6743-6749.

PMID: 22004849;PMCID: PMC3206593;Abstract:

The critical role of Aurora kinase in cell cycle progression and its deregulation in cancer has garnered significant interest. As such, numerous Aurora targeted inhibitors have been developed to date, almost all of which target the ATP cleft at the active site. These current inhibitors display polypharmacology; that is, they target multiple kinases, and some are being actively pursued as therapeutics. Currently, there are no general approaches for targeting Aurora at sites remote from the active site, which in the long term may provide new insights regarding the inhibition of Aurora as well as other protein kinases, and provide pharmacological tools for dissecting Aurora kinase biology. Toward this long term goal, we have recently developed a bivalent selection strategy that allows for the identification of cyclic peptides that target the surface of PKA, while the active site is blocked by an ATP-competitive compound. Herein, we extend this approach to Aurora kinase (Aurora A), which required significant optimization of selection conditions to eliminate background peptides that target the streptavidin matrix upon which the kinases are immobilized. Using our optimized selection conditions, we have successfully selected several cyclic peptide ligands against Aurora A. Two of these inhibitors demonstrated IC 50 values of 10 μM and were further interrogated. The CTRPWWLC peptide was shown to display a noncompetitive mode of inhibition suggesting that alternate sites on Aurora beyond the ATP and peptide substrate binding site may be potentially targeted. © 2011 Elsevier Ltd. All rights reserved.

Ghosh, I., Zhou, M., & Ghosh, I. -. (2004). Noncovalent multivalent assembly of jun peptides on a leucine zipper dendrimer displaying fos peptides. Organic letters, 6(20).

[reaction: see text] The synthesis and characterization of a new leucine-zipper dendrimer (LZD) is reported that displays four copies of the peptide corresponding to the coiled-coiled dimerization domain of Fos. Circular dichroism spectroscopy, fluorescence titration, and sedimentation equilibrium experiments demonstrate that Fos-LZD can noncovalently assemble four copies of the peptide corresponding to the coiled-coil domain of Jun. This work provides the basis for the future construction of noncovalently assembled multivalent protein assemblies displaying any protein of interest.