Professor
Degrees and Appointments
- Postdoctoral Fellow 1998-2001, Yale University, New Haven, Connecticut (Professor Andrew D. Hamilton & Professor Lynne Regan)
- Ph.D. 1992-1998, Purdue University, West Lafayette, Indiana (Professor Jean Chmielewski)
- B.S. 1988-1992, Hobart College, Geneva, New York
Fields of Study: Organic Chemistry, Biochemistry
Research Specialities: Bioanalytical, Bioorganic, Chemical Biology, Materials and Polymer Chemistry, Metabolism, Signaling, and Regulation, Nucleic Acids and Genomes, Protein and Membrane Biochemistry, Structural Biology, Synthesis/Synthetic Methods Development
Awards and Honors:
- Outstanding Faculty Award, Honors College, 2011
- Weed Endowed Chair, 2008
- NSF CAREER Award, 2006
- Research Innovation Award, 2002
- Leukemia Society Fellow, 1999
Research
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.
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) Split-Protein Biosensors for Everything: Direct DNA Detection utilizing Sequence Enabled Reassembly (SEER): We have designed split protein systems that reassemble only in the presence of a specific DNA, modified DNA, or RNA 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 user defined nucleic acid targeting agents. This approach has potential for the direct detection of nucleic acid sequences implicated in human disease but more importantly has the for the design of new cancer therapeutics that respond to changes at the genetic level of an individual cell.
57. Jester, B.W.; Gaj, A.; Shomin, C.D.; Cox, K.J.; Ghosh, I."Testing the Promiscuity of Commercial Kinase Inhibitors against the AGC Kinase Group Using a Split-luciferase Screen" J. Medicinal Chemistry , 2012, ASAP
56. Shekhawat, S.S.; Ghosh, I."Split-Protein Systems: Beyond Binary Protein-Protein Interactions" Current Opinion in Chemical Biology , 2011, 15,789-797
55. Shomin, C.D.; Resituto, E.; Cox, K.J.; Ghosh, I."Selection of cyclic-peptide inhibitors targeting Aurora kinase A: Problems and solutions." Bioorg. Med. Chem., 2011,19,6743-6749
54. Badran, A.H.; Furman, J.L.; Ma, A.S.; Comi, T.J.; Porter, J.R.; Ghosh, I."Evaluating the Global CpG Methylation Status of Native DNA Utilizing a Bipartite Split-Luciferase Sensor" Analytical Chem., 2011,83, 7151-7157
53. Shekhawat, S.S.; Campbell, S.T.; Ghosh, I. "A Comprehensive Panel of Turn-on Caspase Biosensors for Investigating Caspase Specificity and Caspase Activation Pathways" ChemBioChem, 2011,12,2353-2364
52. Furman, J.L.; Mok, P.W.; Badran, A.H.; Ghosh, I. "Turn-on DNA Damage Sensors for the Direct Detection of 8-Oxoguanine and Photoproducts in Native DNA" J. Am. Chem. Soc., 2011,133, 12518-12527(Journal Cover)
51. Kox, K.J.; Shomin, C.D.; Ghosh, I."Tinkering outside the kinase ATP box: allosteric (type IV) and bivalent (type V) inhibitors of protein kinases" Future Med. Chem. , 2011, 3, 29-43
50. Furman, J.L.; Mok, P.W.;Shen,S.; Stains, C. I.; Ghosh, I. "A turn-on split-luciferase sensor for the direct detection of poly(ADP-ribose) as a marker for DNA repair and cell death" Chem. Commun., 2011, 47, 397-399
49. Porter, J.R;Helmers, M.H.;Wang, P.; Furman, J.L.; Arora, P.S.; Ghosh, I. "Profiling Small Molecule Inhibitors against Helix-Receptor Interactions: The Bcl-2 Family Inhibitor BH3I-1 Potently Inhibits p53/hDM2" Chem. Commun., 2010,46, 8020-8022
48. Jester, B.W.;Cox, K.J.;Gaj, A.; Shomin, C.D.; Porter, J.R.; Ghosh, I. "A Coiled Coil Enabled Split-Luciferase Three-Hybrid System: Applied Toward Profiling Inhibitors of Protein Kinases" J. Am. Chem. Soc., 2010, 132, 11727-11735
47. Furman, J.L.;Badran A.H.;Oluyomi A.; Porter, J.R.; Stains, C.I.; Segal, D.J.; Ghosh, I. "A General Approach toward RNA-Templated Hierarchical Assembly of Split-Proteins" J. Am. Chem. Soc., 2010, 132, 11692-11701
46. Stains, C.I.; Furman, J.L.; Porter, J.R.; Rajagopal, S.; Yuxing, L.; Wyatt, R.T.; Ghosh, I. "A General Approach for Receptor and Antibody-Targeted Detection of Native Proteins utilizing Split-Luciferase Reassembly" ACS Chemical Biology, 2010, 5, 943-952
45. Henchey, L.K.; Porter, J.R.; Ghosh, I.; Arora, P.S."High Specificity in Protein Recognition by Hydrogen Bond Surrogate alpha-Helices: Selective Inhibition of the p53/MDM2 Complex" ChemBioChem, 2010, 11,2104-2107
44. Yu, Y.; Blair, S.; Gillespie, D.; Jensen, R.; Myszka, D.; Badran, A.H.; Ghosh, I.; Chagovetz, A. "Direct DNA Methylation Profiling Using Methyl Binding Domain Proteins" Analytical Chemistry, 2010, 82, 5012-5019
43. Meyer, S.C.; Ghosh, I. "Phage Display Technology in Biosensor Development" In Recognition Receptors in Biosensors; Zourob, M., Ed. Springer: New York; 2010, 723-751
42. Porter J.R.; Lockwood S.H.; Segal. D.J.; Ghosh, I."Seeing Genetic and Epigenetic Information without DNA Denaturation Using Sequence Enabled Reassembly (SEER)" Engineered Zinc Finger Proteins: Protocols and Methods: Methods in Molecular Biology 649 Springer: New York; 2010, 649, 365-382
41. 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, 5284-5290
40. Furman, J.L.;Badran, A.H.; Shen, S.; Stains, C.I.;Hannallah, J.; Segal D.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 (special issue for Carlos F. Barbas III/featured Report in Faculty of 1000)
39. 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, 17, 6196-202
38. Deng, Z.; Lie, L.F.; Shen, S.; Ghosh, I.; Mansuripur, M; Muscat, 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, 9, 434-442
37. Porter, J.R.; Stains, C.I.; Jester, B.W.; 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
36. Ghosh, I. Creative Chemical Sensor Systems J. Am. Chem. Soc.(Book Review) 2008, 130, 4570-4571
35. Ghosh, I. Quantum Dots: Applications in Biology ChemBioChem, (Book Review) 2008, 9, 157-158
34. 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 (Featured Report in ACS Chem. Biol., Mol. BioSys., and Faculty of 1000)
33. Stains, C.I.; Ghosh, I. "When Conjugated Polymers meet Amyloid Fibrils" ACS Chemical Biology, 2007, 2, 525-528
32. Stains, C.I.; Mondal, K.; Ghosh, I. "Molecules that Target beta-Amyloid" ChemMedChem, 2007, 2, 1674-1692
31. 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
30. 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
29. 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
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
27. Zhou, M.; Ghosh, I. "Quantum Dots and Peptides: A Bright Future Together" Biopolymers, 2007, 88, 325-339
26. 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
25. Smith, T.J.; Stains, C.I.; Meyer, S.C.; Ghosh, I."Inhibition of beta-Amyloid Fibrillization by Directed Evolution of a beta-Sheet Presenting Miniature Protein"J. Am. Chem. Soc. 2006, 128, 14456 - 14457
24. 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
23. 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
22. Stains, C.I.; Furman, J.L; Segal, D.J.; Ghosh, I. "Site Specific Detection of DNA Methylation utilizing mCPG-SEER" J. Am. Chem. Soc. 2006, 128, 9761-9765
21. 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 (Journal Cover)
20. Ooi, A.T.; Stains, C.I.; Ghosh, I. Segal, D.J. "SEquence-Enabled Reassembly of beta-Lactamase (SEER-LAC): A Sensitive Method for the Detection of Double-Stranded DNA"Biochemistry 2006, 46, 3620-3625
19. Stains, C.I.; Porter, J.R.; Ooi, A.T.; Segal, D.J.; 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. Also featured Report in Faculty of 1000)
18. Magliery , T.; Wilson C.M, Pan, W.; Mishler, D.I.: Ghosh, I.; Hamilton, A.D.;Regan, L. "The scope and mechanism of the GFP fragment-reassembly protein-protein interaction trap" J. Am. Chem. Soc. 2005, 127, 146-157
17. 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
16. 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
15. 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
14. 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)
13. 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