MICHAEL AARON WEISS

Summary

Affiliation: Case Western Reserve University
Country: USA

Publications

  1. pmc Diabetes mellitus due to the toxic misfolding of proinsulin variants
    Michael A Weiss
    Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA
    FEBS Lett 587:1942-50. 2013
  2. pmc Proinsulin and the genetics of diabetes mellitus
    Michael A Weiss
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 284:19159-63. 2009
  3. pmc Enhancing the activity of a protein by stereospecific unfolding: conformational life cycle of insulin and its evolutionary origins
    Qing xin Hua
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 284:14586-96. 2009
  4. ncbi request reprint Non-standard insulin design: structure-activity relationships at the periphery of the insulin receptor
    Michael A Weiss
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    J Mol Biol 315:103-11. 2002
  5. pmc Design of an insulin analog with enhanced receptor binding selectivity: rationale, structure, and therapeutic implications
    Ming Zhao
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 284:32178-87. 2009
  6. ncbi request reprint A protein caught in a kinetic trap: structures and stabilities of insulin disulfide isomers
    Qing xin Hua
    Department of Biochemistry, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
    Biochemistry 41:14700-15. 2002
  7. ncbi request reprint Structure-specific effects of protein topology on cross-beta assembly: studies of insulin fibrillation
    Kun Huang
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Biochemistry 45:10278-93. 2006
  8. pmc Supramolecular protein engineering: design of zinc-stapled insulin hexamers as a long acting depot
    Nelson B Phillips
    Department of Biochemistry, Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Biol Chem 285:11755-9. 2010
  9. pmc Solution structure of proinsulin: connecting domain flexibility and prohormone processing
    Yanwu Yang
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 285:7847-51. 2010
  10. ncbi request reprint Chiral mutagenesis of insulin's hidden receptor-binding surface: structure of an allo-isoleucine(A2) analogue
    Bin Xu
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106 4935, USA
    J Mol Biol 316:435-41. 2002

Research Grants

  1. How Insulin Binds the Insulin Receptor
    Michael Weiss; Fiscal Year: 2006
  2. Biochemical Studies of a Transcription Factor
    MICHAEL AARON WEISS; Fiscal Year: 2010
  3. How Insulin Binds to the Insulin Receptor
    Michael Weiss; Fiscal Year: 2007
  4. Folding of Proinsulin
    Michael Weiss; Fiscal Year: 2007
  5. Insulin Formulations of Enhanced Stability
    Michael Weiss; Fiscal Year: 2007
  6. Biochemical Studies of Worm Insulins
    Michael Weiss; Fiscal Year: 2006
  7. Design of an Implantable Pump Insulin
    Michael Weiss; Fiscal Year: 2009
  8. Design of an Implantable Pump Insulin
    MICHAEL AARON WEISS; Fiscal Year: 2010
  9. How Insulin Binds to the Insulin Receptor
    MICHAEL AARON WEISS; Fiscal Year: 2010
  10. How Insulin Binds to the Insulin Receptor
    MICHAEL AARON WEISS; Fiscal Year: 2010

Collaborators

Detail Information

Publications43

  1. pmc Diabetes mellitus due to the toxic misfolding of proinsulin variants
    Michael A Weiss
    Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA
    FEBS Lett 587:1942-50. 2013
    ..Studies of such mutations suggest that the evolution of insulin has been constrained not only by its structure and function, but also by the susceptibility of its single-chain precursor to impaired foldability...
  2. pmc Proinsulin and the genetics of diabetes mellitus
    Michael A Weiss
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 284:19159-63. 2009
    ..Protein evolution is constrained not only by structure and function but also by susceptibility to toxic misfolding...
  3. pmc Enhancing the activity of a protein by stereospecific unfolding: conformational life cycle of insulin and its evolutionary origins
    Qing xin Hua
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 284:14586-96. 2009
    ..The cryptic threat of misfolding poses a universal constraint in the evolution of polypeptide sequences...
  4. ncbi request reprint Non-standard insulin design: structure-activity relationships at the periphery of the insulin receptor
    Michael A Weiss
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    J Mol Biol 315:103-11. 2002
    ..Dab(A8)-insulin illustrates the utility of non-standard amino acids in hypothesis-driven protein design...
  5. pmc Design of an insulin analog with enhanced receptor binding selectivity: rationale, structure, and therapeutic implications
    Ming Zhao
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 284:32178-87. 2009
    ..Future development of clinical analogs lacking significant IGFR cross-binding may enhance the safety of insulin replacement therapy in patients with type 2 diabetes mellitus at increased risk of colorectal cancer...
  6. ncbi request reprint A protein caught in a kinetic trap: structures and stabilities of insulin disulfide isomers
    Qing xin Hua
    Department of Biochemistry, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
    Biochemistry 41:14700-15. 2002
    ..Structures of metastable disulfide isomers provide probes of the topography of an energy landscape...
  7. ncbi request reprint Structure-specific effects of protein topology on cross-beta assembly: studies of insulin fibrillation
    Kun Huang
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Biochemistry 45:10278-93. 2006
    ..We speculate that the general danger of fibrillation has imposed a constraint in protein evolution, selecting for topologies unfavorable to amyloid formation...
  8. pmc Supramolecular protein engineering: design of zinc-stapled insulin hexamers as a long acting depot
    Nelson B Phillips
    Department of Biochemistry, Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Biol Chem 285:11755-9. 2010
    ..Zinc stapling provides a general strategy to modify the pharmacokinetic and biological properties of a subcutaneous protein depot...
  9. pmc Solution structure of proinsulin: connecting domain flexibility and prohormone processing
    Yanwu Yang
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 285:7847-51. 2010
    ..The structure of proinsulin provides a foundation for studies of insulin biosynthesis and its impairment in monogenic forms of diabetes mellitus...
  10. ncbi request reprint Chiral mutagenesis of insulin's hidden receptor-binding surface: structure of an allo-isoleucine(A2) analogue
    Bin Xu
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106 4935, USA
    J Mol Biol 316:435-41. 2002
    ..We propose that the Ile(A2) side-chain inserts within a chiral pocket of the receptor as part of insulin's hidden functional surface...
  11. pmc An Achilles' heel in an amyloidogenic protein and its repair: insulin fibrillation and therapeutic design
    Yanwu Yang
    From the Departments of Biochemistry Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 285:10806-21. 2010
    ..Together, our studies define an "Achilles' heel" in a globular protein whose repair may enhance the stability of pharmaceutical formulations and broaden their therapeutic deployment in the developing world...
  12. ncbi request reprint The folding nucleus of the insulin superfamily: a flexible peptide model foreshadows the native state
    Qing xin Hua
    Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA
    J Biol Chem 281:28131-42. 2006
    ..The intrinsic conformational propensities of a flexible disulfide-linked peptide thus define a folding nucleus, foreshadowing the structure of the native state...
  13. pmc Decoding the cryptic active conformation of a protein by synthetic photoscanning: insulin inserts a detachable arm between receptor domains
    Bin Xu
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 284:14597-608. 2009
    ..Our studies demonstrate that photoscanning mutagenesis can decode the active conformation of a protein and so illuminate cryptic constraints underlying its evolution...
  14. pmc Design of an active ultrastable single-chain insulin analog: synthesis, structure, and therapeutic implications
    Qing xin Hua
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    J Biol Chem 283:14703-16. 2008
    ..In addition to their biophysical interest, ultrastable SCIs may enhance the safety and efficacy of insulin replacement therapy in the developing world...
  15. ncbi request reprint A conserved histidine in insulin is required for the foldability of human proinsulin: structure and function of an ALAB5 analog
    Qing xin Hua
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106 4935
    J Biol Chem 281:24889-99. 2006
    ....
  16. ncbi request reprint Mechanism of insulin chain combination. Asymmetric roles of A-chain alpha-helices in disulfide pairing
    Qing xin Hua
    Department of Biochemistry, Case Western Reserve School of Medicine, Cleveland, Ohio 44106 4935, USA
    J Biol Chem 277:43443-53. 2002
    ..Implications for the hierarchical folding mechanisms of proinsulin and insulin-like growth factors are discussed...
  17. ncbi request reprint Enhancing the activity of insulin at the receptor interface: crystal structure and photo-cross-linking of A8 analogues
    Zhuli Wan
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 4935, USA
    Biochemistry 43:16119-33. 2004
    ..Optimizing the binding interaction of a nonconserved side chain on the surface of insulin may thus enhance its activity...
  18. pmc A cavity-forming mutation in insulin induces segmental unfolding of a surrounding alpha-helix
    Bin Xu
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    Protein Sci 11:104-16. 2002
    ..The Ala(A2) analog's low biological activity (0.5% relative to the parent monomer) highlights the importance of the A1-A8 alpha-helix in receptor recognition...
  19. ncbi request reprint The hidden thermodynamics of a zinc finger
    Marcel J Lachenmann
    Department of Biochemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 4935, USA
    J Mol Biol 316:969-89. 2002
    ..Exclusion of Leu among biological sequences suggests an evolutionary constraint on the dynamics of a Zn finger...
  20. ncbi request reprint Diabetes-associated mutations in insulin: consecutive residues in the B chain contact distinct domains of the insulin receptor
    Bin Xu
    Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106 4935, USA
    Biochemistry 43:8356-72. 2004
    ..By tethering the N- and C-terminal domains of the extracellular alpha subunit, insulin is proposed to stabilize an active conformation of the disulfide-linked transmembrane tyrosine kinase...
  21. ncbi request reprint Crystal structure of allo-Ile(A2)-insulin, an inactive chiral analogue: implications for the mechanism of receptor binding
    Zhu li Wan
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    Biochemistry 42:12770-83. 2003
    ..This seeming paradox suggests that insulin undergoes a change in conformation to expose Ile(A2) at the hormone-receptor interface...
  22. ncbi request reprint Mechanism of insulin fibrillation: the structure of insulin under amyloidogenic conditions resembles a protein-folding intermediate
    Qing xin Hua
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44016 4935
    J Biol Chem 279:21449-60. 2004
    ..Non-cooperative unfolding of the N-terminal A-chain alpha-helix resembles that observed in models of proinsulin folding intermediates and foreshadows the extensive alpha --> beta transition characteristic of mature fibrils...
  23. ncbi request reprint How insulin binds: the B-chain alpha-helix contacts the L1 beta-helix of the insulin receptor
    Kun Huang
    Department of Biochemistry, Case Western Reserve School of Medicine, Cleveland OH 44106 4935, USA
    J Mol Biol 341:529-50. 2004
    ..Together, our results support a model in which the B-chain alpha-helix, functioning as an essential recognition element, docks against the L1 beta-helix of the insulin receptor...
  24. ncbi request reprint The A-chain of insulin contacts the insert domain of the insulin receptor. Photo-cross-linking and mutagenesis of a diabetes-related crevice
    Kun Huang
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 282:35337-49. 2007
    ..Our results provide evidence that Val(A3), a site of mutation causing diabetes mellitus, contacts the insert domain-derived tail of the alpha-subunit in a hormone-receptor complex...
  25. doi request reprint Doublesex and the regulation of sexual dimorphism in Drosophila melanogaster: structure, function, and mutagenesis of a female-specific domain
    Yanwu Yang
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 283:7280-92. 2008
    ..These mutations confer graded gene-regulatory activity in yeast within a physiological temperature range and so may provide novel probes for genetic analysis of a sex-specific transcriptional program in Drosophila development...
  26. ncbi request reprint Why zinc fingers prefer zinc: ligand-field symmetry and the hidden thermodynamics of metal ion selectivity
    Marcel J Lachenmann
    Department of Biochemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106 4935, USA
    Biochemistry 43:13910-25. 2004
    ..Together, these considerations indicate that LFSE provides an important but incomplete description of the stringency and thermodynamic origin of metal-ion selectivity...
  27. pmc A divergent INS protein in Caenorhabditis elegans structurally resembles human insulin and activates the human insulin receptor
    Qing xin Hua
    Department of Biochemistry, Case Western Reserve School of Medicine, Cleveland, OH 44106, USA
    Genes Dev 17:826-31. 2003
    ..Although lacking classical receptor-binding determinants, INS-6 binds to and activates the human insulin receptor. Its activity is greater than that of an analogous single-chain human insulin analog...
  28. ncbi request reprint Diabetes mellitus due to misfolding of a beta-cell transcription factor: stereospecific frustration of a Schellman motif in HNF-1alpha
    Narendra Narayana
    Department of Biochemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 4935, USA
    J Mol Biol 362:414-29. 2006
    ..Comparison of L- and D amino acid substitutions thus provides an example of the stereospecific control of an energy landscape by a helix-capping residue...
  29. pmc The structure of a mutant insulin uncouples receptor binding from protein allostery. An electrostatic block to the TR transition
    Zhu li Wan
    Departments of Biochemistry and Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    J Biol Chem 283:21198-210. 2008
    ..The substantial receptor-binding activity of Arg(B5)-insulin (40% relative to wild type) demonstrates that the function of an insulin monomer can be uncoupled from its allosteric reorganization within zinc-stabilized hexamers...
  30. ncbi request reprint Dimerization of doublesex is mediated by a cryptic ubiquitin-associated domain fold: implications for sex-specific gene regulation
    James R Bayrer
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Biol Chem 280:32989-96. 2005
    ..The possibility that the ubiquitination machinery participates in the regulation of sexual dimorphism is discussed...
  31. pmc Regulation of sexual dimorphism: mutational and chemogenetic analysis of the doublesex DM domain
    Wei Zhang
    Case Western Reserve School of Medicine, Department of Biochemistry, 10900 Euclid Ave, Cleveland, Ohio 44106 4935, USA
    Mol Cell Biol 26:535-47. 2006
    ..Together, these results provide molecular links between the structure of the DM domain and its function in the regulation of sexual dimorphism...
  32. ncbi request reprint Diabetes-associated mutations in human insulin: crystal structure and photo-cross-linking studies of a-chain variant insulin Wakayama
    Zhu li Wan
    Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106 4935, USA
    Biochemistry 44:5000-16. 2005
    ....
  33. ncbi request reprint Proinsulin is refractory to protein fibrillation: topological protection of a precursor protein from cross-beta assembly
    Kun Huang
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 280:42345-55. 2005
    ..In addition to its classic function to facilitate disulfide pairing, the connecting peptide may protect beta cells from toxic protein misfolding in the endoplasmic reticulum...
  34. pmc The structure and function of insulin: decoding the TR transition
    Michael A Weiss
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Vitam Horm 80:33-49. 2009
    ..C. Hodgkin. Future studies of the receptor-bound structure of insulin may enable design of novel agonists for the treatment of diabetes mellitus...
  35. ncbi request reprint Protein structure and the spandrels of San Marco: insulin's receptor-binding surface is buttressed by an invariant leucine essential for its stability
    Michael A Weiss
    Department of Biochemistry, Case Western Reserve School of Medicine, Cleveland, Ohio 44106 4935, USA
    Biochemistry 41:809-19. 2002
    ..This celebrated metaphor of Gould and Lewontin emphasizes the role of interlocking constraints in the evolution of biological structures...
  36. ncbi request reprint SRY and human sex determination: the basic tail of the HMG box functions as a kinetic clamp to augment DNA bending
    Nelson B Phillips
    Department of Biochemistry, Case School of Medicine, Case Western Reserve University, Cleveland, OH 44106 4935, USA
    J Mol Biol 358:172-92. 2006
    ..We speculate that the kinetic stability of a bent DNA complex is critical to the assembly and maintenance of a sex-specific transcriptional pre-initiation complex...
  37. ncbi request reprint Insulin assembly damps conformational fluctuations: Raman analysis of amide I linewidths in native states and fibrils
    Jian Dong
    Department of Biochemistry, Case Western Reserve University School of Medicine, 10900 Euclid Avenue SOM W427, Cleveland, OH 44106 4935, USA
    J Mol Biol 330:431-42. 2003
    ..Enhanced flexibility of the native insulin monomer is in accord with molecular dynamics simulations. Such conformational fluctuations may initiate formation of an amyloidogenic nucleus and enable induced fit on receptor binding...
  38. ncbi request reprint Expression, crystallization and preliminary X-ray characterization of the Drosophila transcription factor Doublesex
    James Bayrer
    Case Western Reserve University, Cleveland, Ohio, USA
    Acta Crystallogr D Biol Crystallogr 60:1328-30. 2004
    ..Native crystals belong to space group P2(1)2(1)2(1) and diffract to a resolution of 1.6 A with synchrotron radiation. Selenomethionine-containing crystals provide anomalous dispersion for phasing...
  39. pmc Crystallographic analysis of a sex-specific enhancer element: sequence-dependent DNA structure, hydration, and dynamics
    Narendra Narayana
    Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA
    J Mol Biol 385:469-90. 2009
    ..We speculate that sites of intrinsic flexibility within a DNA control element provide hinges for its protein-directed reorganization in a transcriptional preinitiation complex...
  40. ncbi request reprint SRY-directed DNA bending and human sex reversal: reassessment of a clinical mutation uncovers a global coupling between the HMG box and its tail
    Biaoru Li
    Department of Biochemistry, Case School of Medicine, Case Western Reserve University, Cleveland, OH 44106 4935, USA
    J Mol Biol 360:310-28. 2006
    ..The previously unsuspected role of M64 within a non-classical NLS may contribute to its invariance among SOX-related and LEF-1-related transcription factors...
  41. ncbi request reprint Diabetes-associated mutations in insulin identify invariant receptor contacts
    Bin Xu
    Case Western Reserve University, Department of Biochemistry, 10900 Euclid Ave, SOM Room W427, Cleveland, OH 44106 4935, USA
    Diabetes 53:1599-602. 2004
    ..Our results demonstrate that this surface spans both chains of the insulin molecule and includes sites of rare human mutations that cause diabetes...
  42. ncbi request reprint Toward the active conformation of insulin: stereospecific modulation of a structural switch in the B chain
    Qing xin Hua
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 281:24900-9. 2006
    ..The inverse relationship between stereospecific stabilization and receptor binding strongly suggests that the B7-B10 beta-turn changes conformation on receptor binding...
  43. ncbi request reprint Sry-directed sex reversal in transgenic mice is robust with respect to enhanced DNA bending: comparison of human and murine HMG boxes
    Nelson B Phillips
    Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106 4935, USA
    Biochemistry 43:7066-81. 2004
    ..We propose that male-specific gene regulation requires DNA bending above a critical threshold set by architectural requirements of enhanceosome assembly...

Research Grants42

  1. How Insulin Binds the Insulin Receptor
    Michael Weiss; Fiscal Year: 2006
    ..Bass (Northwestern University). Aim 4 focuses on co-crystallization studies of the hormone-receptor complex with the Dodson laboratory. Each aim is supported by a solid foundation of preliminary results. ..
  2. Biochemical Studies of a Transcription Factor
    MICHAEL AARON WEISS; Fiscal Year: 2010
    ..We are studying sex-specific genes in fruit flies to gain insight into human birth defects, infertility syndromes, and cancers of the gonads. ..
  3. How Insulin Binds to the Insulin Receptor
    Michael Weiss; Fiscal Year: 2007
    ..To demonstrate proof-of- principle, respective application of this enabling technology to the liver and pancreatic p cells of LIRKO and PIRKO mice is planned in collaboration with C. R. Kahn (Joslin Diabetes Center, Boston). ..
  4. Folding of Proinsulin
    Michael Weiss; Fiscal Year: 2007
    ..Our results promise to have implications for the evolution of insulin-like sequences and the possible misfolding of human proinsulin in type II diabetes mellitus. ..
  5. Insulin Formulations of Enhanced Stability
    Michael Weiss; Fiscal Year: 2007
    ..Accordingly, our strategy may generalize to enhance the utility of diverse protein pharmaceuticals in the post-genomic era. ..
  6. Biochemical Studies of Worm Insulins
    Michael Weiss; Fiscal Year: 2006
    ..abstract_text> ..
  7. Design of an Implantable Pump Insulin
    Michael Weiss; Fiscal Year: 2009
    ..The objective of this application is to design an optimal insulin analog for safe and effective use in an implantable pump. ..
  8. Design of an Implantable Pump Insulin
    MICHAEL AARON WEISS; Fiscal Year: 2010
    ..Design principles will be validated through a series of functional assays and molecular studies to provide a solid scientific foundation for clinical translation. ..
  9. How Insulin Binds to the Insulin Receptor
    MICHAEL AARON WEISS; Fiscal Year: 2010
    ..R. Kahn (Joslin Diabetes Center, Boston). ..
  10. How Insulin Binds to the Insulin Receptor
    MICHAEL AARON WEISS; Fiscal Year: 2010
    ..To demonstrate proof-of- principle, respective application of this enabling technology to the liver and pancreatic p cells of LIRKO and PIRKO mice is planned in collaboration with C. R. Kahn (Joslin Diabetes Center, Boston). ..
  11. Biochemical Studies of a Transcription Factor
    MICHAEL AARON WEISS; Fiscal Year: 2010
    ..We are studying sex-specific genes in fruit flies to gain insight into human birth defects, infertility syndromes, and cancers of the gonads. ..
  12. Design of an Implantable Pump Insulin
    MICHAEL AARON WEISS; Fiscal Year: 2010
    ..The objective of this application is to design an optimal insulin analog for safe and effective use in an implantable pump. ..
  13. How Insulin Binds to the Insulin Receptor
    Michael Weiss; Fiscal Year: 2009
    ..To demonstrate proof-of- principle, respective application of this enabling technology to the liver and pancreatic p cells of LIRKO and PIRKO mice is planned in collaboration with C. R. Kahn (Joslin Diabetes Center, Boston). ..
  14. Insulin Formulations of Enhanced Stability
    Michael Weiss; Fiscal Year: 2009
    ..Accordingly, our strategy may generalize to enhance the utility of diverse protein pharmaceuticals in the post-genomic era. ..
  15. NMR STUDIES OF MUTANT INSULINS ASSOCIATED WITH DIABETES
    Michael Weiss; Fiscal Year: 2001
    ..This information is of basic importance in protein chemistry and likely to facilitate design of novel insulin for the treatment of diabetes mellitus. ..
  16. TRANSCRIPTION RELATED STRUCTURAL MODULES
    Michael Weiss; Fiscal Year: 2001
    ..The systems under study are of broad biological interest with application to cancer biology and AIDS. ..
  17. VP ITC MICROCALORIMETER AND A VP DSC MICROCALORIMETER
    Michael Weiss; Fiscal Year: 2001
    ..The requested instruments will therefore significantly enhance the depth and scope of the major users' funded research and will provide general access to state-of-the-art calorimetric analysis to the University community...
  18. Ultra-shielded 600 MHz NMR spectrometer with a cryprobe
    Michael Weiss; Fiscal Year: 2002
    ..It will not only make an impact on research projects of Cleveland structural biology community but also create an active core of NMR structural biology experts trained in the most current and sophisticated techniques. ..
  19. How Insulin Binds the Insulin Receptor
    Michael Weiss; Fiscal Year: 2003
    ..Bass (Northwestern University). Aim 4 focuses on co-crystallization studies of the hormone-receptor complex with the Dodson laboratory. Each aim is supported by a solid foundation of preliminary results. ..
  20. PROTEIN FOLDING AND MISFOLDING
    Michael Weiss; Fiscal Year: 2003
    ..This differential property is the basis on which Dr. Weiss proposes to identify factors responsible for on-pathway and off-pathway oxidative folding. ..
  21. Proteomics Reagents in Diabetes & Metabolism
    Michael Weiss; Fiscal Year: 2003
    ..The proposed pilot studies will dissect an insulin signaling pathway in a genetic model of senescence and aging (Aim 1) and a novel mechanism of metabolic homeostasis and insulin resistance in human obesity. ..