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Indraneel GhoshWeed endowed Chair, Associate Professor of Chemistry Associate Professor of Biochemistry and Molecular Biophysics Associate Professor, BIO5 Institute for Collaborative Research ghosh@email.arizona.edu Chemical Sciences Building 410 Phone: (520) 621-6331 Fax: (520) 621-8407 |
Honors
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Education and Appointments
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Research Interests
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Research Summary | |
Bioorganic Chemistry and Chemical Biology Our group focuses upon: A) Designing Inhibitors of Protein/Protein Interactions B) Constructing Macromolecules and Quantum Dots with Novel Functions C) Designing Biosensors for the Direct Detection of DNA (SEER) 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 A) Targeted Therapeutics for Human Disease by Inhibition of Protein-Protein Interactions: We are developing novel therapeutics targeted towards protein-protein interactions utilizing evolved β-sheet scaffolds. We utilize a novel dual-surface selection phage-display methodology for identifying thermostable variants of small proteins that serve as rigid receptors for targeting a) gp120 (HIV AIDS); b) vascular endothelial growth factor (Cancer), c) thrombin (Heart Disease;) and d) beta-amyloid (Alzheimer's). Our receptors in principle can modulate and impair the in vitro and in vivo activities of the targeted proteins. Specific amino-acid residues selected from phage-display can be grafted upon small synthetic scaffolds. 
B) Helical Supramolecules and Quantum Dots: We have recently constructed a new family of discrete supramolecules comprising designed peptides (coiled-coils) non-covalently assembled upon cognate peptides fused to a dendrimer core. These novel structures are being utilized for the multivalent display of proteins for protein inhibition and in the construction of novel biomaterials. We are also pursuing new approaches for labeling Quantum Dots with peptides to provide a means to image receptors on living cells. 
C) Biosensors: Direct DNA Detection utilizing Sequence Enabled Reassembly (SEER): We have designed split protein systems that reassemble only in the presence of a specific DNA sequence to allow for its direct detection. This approach utilizes rationally dissected proteins, such as the Green Fluorescent Protein (GFP), beta-Lactamase, and luciferase for construction of oligomerization-dependent protein reassembly systems and designed DNA binding Cys2-His2, zinc finger motifs for targeting specific sequences of double-stranded DNA. This approach has potential for detection of a) DNA sequence repeats implicated in human disease; and b)human pathogens. We have also designed detection systems for the direct read out of specific sites of DNA that are methylated. This is an important area, as DNA methylation is intimately involved in transcriptional regulation and the deregulation of DNA methylation strongly correlates with the development of cancer.  | |
Selected Publications | |
| Shekhawat, S. S.; Porter, J. R.; Sriprasad, A.; Ghosh. I. “An Autoinhibited Coiled-Coil Design Strategy for Split-Protein Protease Sensors” J. Am. Chem. Soc. 2009 ,131, 15284-15290
Shomin C. D; Meyer. S. C.; Ghosh, I. “Staurosporine Tethered Peptide Ligands that Target cAMP-dependent Protein Kinase (PKA): Optimization and Selectivity Profiling” Bioorg. Med. Chem. 2009 , 19, 6196-6202
Furman, J. L.; Badran, A. H.; Shen, S.; Stains, C. I.; Hannallah, J.; Ghosh, I. “Systematic Evaluation of Split-Fluorescent Proteins for the Direct Detection of Native and Methylated DNA” Bioorg. Med. Chem. Lett. 2009 , 19, 3748-51 (Highlighted in Faculty of 1000)
Deng, Z.; Lie, L. F.; Shen, S.;Ghosh, I.;Mansuripur. M; Muscta, A. J."Water-Based Route to Ligand-Selective Synthesis of ZnSe and Cd-Doped ZnSe Quantum Dots with Tunable Ultraviolet A to Blue Photoluminescence" Langmuir 2009, 29, 434-442
Porter, J. R.; Stains, C. I.; Jester, B.; Ghosh, I. “A General and Rapid Cell-Free Approach for the Interrogation of Protein-Protein, Protein-DNA and Protein-RNA Interactions and their Antagonists Utilizing Split-Protein Reporters” J. Am. Chem. Soc. 2008, 130, 6488-6497
Ghosh, I. Creative Chemical Sensor Systems J. Am. Chem. Soc.(Book Review) 2008, 130, 4570-4571
Ghosh, I. Quantum Dots: Applications in Biology ChemBioChem, (Book Review) 2008, 9, 157-158
Meyer, S. C.; Shomin, C. D.; Gaj, T.; Ghosh, I. "Tethering Small Molecules to a Phage Display Library: Discovery of a Selective Bivalent Inhibitor of Protein Kinase A" J. Am. Chem. Soc. 2007, 129, 13812-13813
Stains, C. I.; Ghosh, I. “When Conjugated Polymers meet Amyloid Fibrils” ACS Chemical Biology, 2007, 2, 525-528
Stains, C. I.; Mondal, K.; Ghosh, I. “Molecules that Target beta-Amyloid” ChemMedChem, 2007, 2, 1674-1692
Porter, J. R.; Stains, C. I.; Segal, D. J.; Ghosh, I. “Split beta-Lactamase Sensor for the Sequence-Specific Detection of DNA Methylation” Analytical Chemistry, 2007, 79, 6702-6708
Gaj, T.; Meyer, S. C.; Ghosh, I. “The AviD-tag, a NeutrAvidin/avidin Specific Peptide Affinity Tag for the Immobilization and Purification of Recombinant Proteins” Protein Expression & Purification, 2007,56,54-61
Ghosh, I.; Wirth M.J. "Parsing the Motion of Single Molecules: A Novel Algorithm for Deconvoluting the Dynamics of Individual Receptors at the Cell Surface," Science's STKE, 2007,388, 28
Zhou, M.; Nakatani, E.; Gronenberg, L.S.; Tokimoto, T.; Wirth, M.J.; Hruby, V.J.; Roberts, A.; Lynch, R.M.; Ghosh, I. "Peptide-Labeled Quantum Dots for Imaging GPCRs in Whole Cells and as Single Molecules,"
Bioconjugate Chem., 2007, 18 (2), 323 -332
Zhou, M.; Ghosh, I. "Quantum Dots and Peptides: A Bright Future Together," Biopolymers, 2007, 88, 325-339
Tokimoto, T.; Bethea, T.R.C.; Zhou, M.; Ghosh, I.; Wirth M.J. "Probing orientations of single fluorescent labels on a peptide reversibly binding to the human delta-opioid receptor,"
Applied Spectroscopy, 2007, 61, 130-137
Smith, T. J.; Stains, C. I.; Meyer, S. C.; Ghosh, I."Inhibition of β-Amyloid Fibrillization by Directed Evolution of a β-Sheet Presenting Miniature Protein"
J. Am. Chem. Soc. 2006, 128, 14456 - 14457
Ghosh,I.; Stains, C. I.; Ooi, A. T.; Segal, D. J. "Direct detection of double-stranded DNA: molecular methods and applications for DNA diagnostics"
Mol.BioSyst. 2006, 2, 551-560
Rajagopal, S.; Meyer, S. C.; Goldman, A.; Zhou, M.; Ghosh, I."A Minimalist Approach toward Protein Recognition by Epitope Transfer from Functionally Evolved Beta-Sheet Surfaces"
J. Am. Chem. Soc. 2006, 128, 14356-14363
Stains, C.A.; Furman, J. Segal, D.; Ghosh, I. " Site Specific Detection of DNA Methylation utilizing mCPG-SEER"
J. Am. Chem. Soc. 2006, 128, 9761-9765
Meyer, S. C.; Gaj, T.; Ghosh, I. "Highly Selective Cyclic Peptide Ligands for NeutrAvidin and Avidin Identified by Phage Display"
Chem. Biol. & Drug Des. 2006, 68, 3-10
Ooi, A. T.; Stains, C.A.; Ghosh, I. Segal, D. "SEquence-Enabled Reassembly of beta-Lactamase (SEER-LAC): A Sensitive Method for the Detection of Double-Stranded DNA"
Biochemistry 2006, 46, 3620-3625
Stains, C.A.; Porter, J.; Ooi, A. T.; Segal, D.; Ghosh, I. "DNA Sequence-Enabled Reassembly of the Green Fluorescent Protein"
J. Am. Chem. Soc. 2005, 127, 10782-10783
(Featured Report in Nature Methods "DNA Makes GFP Shine," 2005, 2, 644)
Magliery , T.; Wilson C. M, Pan, W.; Mishler, D. I.: Ghosh, I.; , Hamilton, A.D.; and Regan, L. "The scope and mechanism of the GFP fragment-reassembly protein-protein interaction trap"
J. Am. Chem. Soc. 2005, 127, 146-157
Meyer, S.C.; Huerta, C.; Ghosh, I., "Single-Site Mutations in a Hyperthermophilic Variant of the B1 Domain of Protein G Result in Self-Assembled Oligomers"
Biochemistry, 2005, 44, 2360-2368
Ghosh, I. "Celebrating Victor Hruby's 65th birthday: An Odyssey in Chemistry and Biology"
Med Res Rev, 2005, 25:487-489 Forward for Special Issue
Ghosh, I. and Chmielewski, J. "Peptide self-assembly as a model of proteins in the pre-genomic world"
Curr. Opin. Chem. Biol. 2004, 8, 640-644
Zhou, M.; Ghosh, I., "Non-covalent Multivalent Assembly of Jun Peptides on a Leucine Zipper Dendrimer Displaying Fos Peptides"
Org. Lett., 2004, 6, 3561-3564
Rajagopal, S; Meza-Romero, R; Ghosh, I. "Dual surface selection methodology for the identification of thrombin binding epitopes from hotspot biased phage-display libraries"
Bioorg. Med. Chem. Lett., 2004, 16, 1389-1393
(Featured 2004 Journal Cover)
Zhou, M; Ghosh, I. "Helical supramolecules and fibers utilizing leucine-zipper displaying dendrimers"
J. Am. Chem. Soc., 2004, 126, 734-735
(Research Highlighted in Chem. & Eng. News, 2004, 82, 41)
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