Michael CzechSummaryAffiliation: University of Massachusetts Medical School Country: USA Publications
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Publications
RNAi-based therapeutic strategies for metabolic diseaseMichael P Czech
University of Massachusetts Medical School, Worcester, MA 01605, USA
Nat Rev Endocrinol 7:473-84. 2011..Although still at an early stage, the emergence of RNAi-based therapeutics has the potential to markedly influence our clinical future...
Dynamics of phosphoinositides in membrane retrieval and insertionMichael P Czech
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Annu Rev Physiol 65:791-815. 2003..The phosphoinositides thereby control many cell features that depend upon protein sorting, including the composition of the plasma membrane itself, which in turn determines the cell's responses to its environment...
Insulin's expanding control of forkheadsMichael P Czech
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Proc Natl Acad Sci U S A 100:11198-200. 2003
Structural basis and mechanism of autoregulation in 3-phosphoinositide-dependent Grp1 family Arf GTPase exchange factorsJonathan P DiNitto
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Mol Cell 28:569-83. 2007..These observations suggest that Grp1 family GEFs are autoregulated by mechanisms that depend on plasma membrane recruitment for activation...
Identification of WNK1 as a substrate of Akt/protein kinase B and a negative regulator of insulin-stimulated mitogenesis in 3T3-L1 cellsZhen Y Jiang
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Biol Chem 280:21622-8. 2005..These data suggest that WNK1 is a physiologically relevant target of insulin signaling through PI3K and Akt/PKB and functions as a negative regulator of insulin-stimulated mitogenesis...
A novel pleckstrin homology domain-containing protein enhances insulin-stimulated Akt phosphorylation and GLUT4 translocation in adipocytesQiong L Zhou
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Biol Chem 285:27581-9. 2010..These results indicate that PHLDB1 is a novel modulator of Akt protein kinase activation by insulin...
Conventional kinesin KIF5B mediates insulin-stimulated GLUT4 movements on microtubulesSabina Semiz
Program in Molecular Medicine, 373 Plantation Street, University of Massachusetts Medical School, Worcester 01605, USA
EMBO J 22:2387-99. 2003..This insulin signaling pathway regulating KIF5B function appears to be required for GLUT4 translocation to the plasma membrane...
Glucose transporter recycling in response to insulin is facilitated by myosin Myo1cAvirup Bose
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Nature 420:821-4. 2002..Thus, myosin Myo1c functions in a PI(3)K-independent insulin signalling pathway that controls the movement of intracellular GLUT4-containing vesicles to the plasma membrane...
Akt substrate TBC1D1 regulates GLUT1 expression through the mTOR pathway in 3T3-L1 adipocytesQiong L Zhou
Programme in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA
Biochem J 411:647-55. 2008..Taken together, our data suggest that TBC1D1 may be involved in controlling GLUT1 glucose transporter expression through the mTOR-p70 S6 kinase pathway...
Role of EHD1 and EHBP1 in perinuclear sorting and insulin-regulated GLUT4 recycling in 3T3-L1 adipocytesAdilson Guilherme
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Biol Chem 279:40062-75. 2004..Taken together, these results show that EHD1 and EHBP1, but not EHD2, are required for perinuclear localization of GLUT4 and reveal that loss of EHBP1 disrupts insulin-regulated GLUT4 recycling in cultured adipocytes...
Insulin stimulates membrane fusion and GLUT4 accumulation in clathrin coats on adipocyte plasma membranesShaohui Huang
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Mol Cell Biol 27:3456-69. 2007....
The GLUT4 glucose transporterShaohui Huang
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Cell Metab 5:237-52. 2007..The principal glucose transporter protein that mediates this uptake is GLUT4, which plays a key role in regulating whole body glucose homeostasis. This review focuses on recent advances on the biology of GLUT4...
Phosphatidylinositol-4,5-bisphosphate-rich plasma membrane patches organize active zones of endocytosis and ruffling in cultured adipocytesShaohui Huang
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation St, Worcester, MA 01605, USA
Mol Cell Biol 24:9102-23. 2004..These results are consistent with the hypothesis that PRMPs organize active PtdIns(4,5)P2 signaling zones in the adipocyte plasma membrane that in turn control regulators of endocytosis, actin dynamics, and membrane ruffling...
EHD2 and the novel EH domain binding protein EHBP1 couple endocytosis to the actin cytoskeletonAdilson Guilherme
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Biol Chem 279:10593-605. 2004..Thus EHD2 appears to connect endocytosis to the actin cytoskeleton through interactions of its N-terminal domain with membranes and its C-terminal EH domain with the novel EHBP1 protein...
Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammationTimothy P Fitzgibbons
Program in Molecular Medicine, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Am J Physiol Heart Circ Physiol 301:H1425-37. 2011....
RNAi-based gene silencing in primary mouse and human adipose tissuesVishwajeet Puri
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
J Lipid Res 48:465-71. 2007..This ex-vivo method of gene silencing should be useful in rapid validation studies as well as in addressing the depot- and species-specific functions of genes in adipose biology...
Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetesAdilson Guilherme
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Nat Rev Mol Cell Biol 9:367-77. 2008....
A Rictor-Myo1c complex participates in dynamic cortical actin events in 3T3-L1 adipocytesG Nana Hagan
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA
Mol Cell Biol 28:4215-26. 2008..Taken together, our findings suggest that the Rictor-Myo1c complex is distinct from mTORC2 and that Myo1c, in conjunction with Rictor, participates in cortical actin remodeling events...
Paradoxical effect of mitochondrial respiratory chain impairment on insulin signaling and glucose transport in adipose cellsXiarong Shi
University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Biol Chem 283:30658-67. 2008..These results indicate that mitochondrial respiratory chain dysfunction in adipocytes can cause impaired insulin responsiveness of GLUT4 translocation by a mechanism downstream of the Akt protein kinase...
A PP2A regulatory subunit regulates C. elegans insulin/IGF-1 signaling by modulating AKT-1 phosphorylationSrivatsan Padmanabhan
University of Massachusetts Medical School, Worcester, 01605, USA
Cell 136:939-51. 2009..This study reveals a conserved role for the B56 regulatory subunit in regulating insulin signaling through AKT dephosphorylation, thereby having widespread implications in cancer and diabetes research...
An RNA interference-based screen identifies MAP4K4/NIK as a negative regulator of PPARgamma, adipogenesis, and insulin-responsive hexose transportXiaoqing Tang
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Proc Natl Acad Sci U S A 103:2087-92. 2006..These results reveal a MAP4K4/NIK-dependent signaling pathway that potently inhibits PPARgamma-responsive gene expression, adipogenesis, and insulin-stimulated glucose transport...
A phosphatidylinositol 3-kinase-independent insulin signaling pathway to N-WASP/Arp2/3/F-actin required for GLUT4 glucose transporter recyclingZhen Y Jiang
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Biol Chem 277:509-15. 2002..These findings reveal that N-WASP likely functions downstream of TC10 in a PI 3-kinase-independent insulin signaling pathway to mobilize cortical F-actin, which in turn promotes GLUT4 responsiveness to insulin...
An essential role of the JIP1 scaffold protein for JNK activation in adipose tissueAnja Jaeschke
Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester 01605, USA
Genes Dev 18:1976-80. 2004..These data identify JIP1 as a novel molecular target for therapeutic intervention in the development of obesity...
Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazoneLeanne Wilson-Fritch
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, 01601, USA
J Clin Invest 114:1281-9. 2004....
Unconventional myosin Myo1c promotes membrane fusion in a regulated exocytic pathwayAvirup Bose
Program in Molecular Medicine, Department of Physiology, University of Massachusetts Medical School, Worcester, 01605, USA
Mol Cell Biol 24:5447-58. 2004..Thus, localized membrane remodeling driven by the Myo1c motor appears to facilitate the fusion of exocytic GLUT4-containing vesicles with the adipocyte plasma membrane...
Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencingZhen Y Jiang
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA
Proc Natl Acad Sci U S A 100:7569-74. 2003....
Early growth response gene-2, a zinc-finger transcription factor, is required for full induction of clonal anergy in CD4+ T cellsJohn E Harris
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
J Immunol 173:7331-8. 2004..These data indicate that sustained Egr-2 expression is necessary to induce a full anergic state through the actions of genes regulated by this transcription factor...
Fat targets for insulin signalingMichael P Czech
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Mol Cell 9:695-6. 2002..New data reveal that insulin may regulate this process in part by promoting membrane trafficking of intracellular fatty acid transporters FATP1 and FATP4 to the plasma membrane...
PTEN, but not SHIP2, suppresses insulin signaling through the phosphatidylinositol 3-kinase/Akt pathway in 3T3-L1 adipocytesXiaoqing Tang
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA
J Biol Chem 280:22523-9. 2005..Taken together, these results demonstrate that endogenous PTEN functions as a suppressor of insulin signaling to glucose transport through the PI 3-kinase pathway in cultured 3T3-L1 adipocytes...
The v-SNARE Vti1a regulates insulin-stimulated glucose transport and Acrp30 secretion in 3T3-L1 adipocytesAvirup Bose
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Biol Chem 280:36946-51. 2005..Taken together, these results suggest that the v-SNARE Vti1a may regulate a step common to both GLUT4 and Acrp30 trafficking in 3T3-L1 adipocytes...
Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytesAimee M Powelka
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Clin Invest 116:125-36. 2006..We conclude that RIP140 is a major suppressor of adipocyte oxidative metabolism and mitochondrial biogenesis, as well as a negative regulator of whole-body glucose tolerance and energy expenditure in mice...
RNAi-based analysis of CAP, Cbl, and CrkII function in the regulation of GLUT4 by insulinPrasenjit Mitra
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Biol Chem 279:37431-5. 2004..These data are consistent with the hypothesis that CAP, Cbl iso-forms, and CrkII are not required components of insulin signaling to GLUT4 transporters...
Micromanaging insulin secretionCraig C Mello
Nat Med 10:1297-8. 2004
Liver X receptor alpha is a transcriptional repressor of the uncoupling protein 1 gene and the brown fat phenotypeHaibo Wang
The Hamner Institutes for Health Sciences, 6 Davis Drive, P O Box 12137, Research Triangle Park, NC 27709, USA
Mol Cell Biol 28:2187-200. 2008..The ability of LXRalpha to dampen energy expenditure in this way provides another mechanism for maintaining a balance between energy storage and utilization...
The interaction of Akt with APPL1 is required for insulin-stimulated Glut4 translocationTsugumichi Saito
Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Biol Chem 282:32280-7. 2007..These data suggest that APPL1 plays an important role in insulin-stimulated Glut4 translocation in muscle and adipose tissues and that its N-terminal portion may be critical for APPL1 function...
ARNT misbehavin' in diabetic beta cellsMichael P Czech
Nat Med 12:39-40. 2006
Research Grants
- Insulin Signaling and Metabolic Regulation in AdipocytesMichael P Czech; Fiscal Year: 2010..These studies will reveal underlying mechanisms of action of these novel global regulators of adipocyte metabolism and function. ..
- Diabetes Mellitus:Molecular Signaling,Genes/TherapeuticsMichael Czech; Fiscal Year: 2004..The proposed meeting is therefore very timely and poised to make an important contribution to the field by fostering unique collaborative interactions between basic and physician scientists. ..
- PROPERTIES OF THE HIGH AFFINITY INSULIN RECEPTORMichael Czech; Fiscal Year: 2003..The experiments proposed may define a new paradigm for insulin signaling that involves the GTP-binding ARF proteins, and reveal novel elements in this signaling pathway. ..
- Insulin Signaling to GLUT4 and the Actin CytoskeletonMichael Czech; Fiscal Year: 2007..Together, these experiments will clarify the role of Myo1c and the actin cytoskeleton in GLUT4 regulation by insulin. ..
- PROPERTIES OF THE HIGH AFFINITY INSULIN RECEPTORMichael Czech; Fiscal Year: 2007..These studies will likely identify novel components of insulin signaling and GLUT4 regulation as well as reveal new mechanisms that mediate these processes. ..
- Oral Delivery Vehicles for RNAi TherapiesMichael P Czech; Fiscal Year: 2010....
- Insulin Signaling and Metabolic Regulation in AdipocytesMichael P Czech; Fiscal Year: 2010..These studies will reveal underlying mechanisms of action of these novel global regulators of adipocyte metabolism and function. ..
- INSULIN ACTION ON THE FAT CELL SURFACE MEMBRANEMichael Czech; Fiscal Year: 1993..In these studies, we shall attempt to absorb and isolate transporter regulator proteins that suppress transport activity in control adipocytes...
- INSULIN ACTION ON THE FAT CELL SURFACE MEMBRANEMichael Czech; Fiscal Year: 1990..These studies on transporter regulation by insulin should allow detailed molecular comparisons with mechanisms involved in IGF-II and transferrin receptor up-regulation...
- PROPERTIES OF THE HIGH AFFINITY INSULIN RECEPTORMichael Czech; Fiscal Year: 1992....
