Jake A Kushner

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. pmc Pdx1 restores beta cell function in Irs2 knockout mice
    Jake A Kushner
    Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 109:1193-201. 2002
  2. pmc Cyclins D2 and D1 are essential for postnatal pancreatic beta-cell growth
    Jake A Kushner
    Division of Endocrinology, Children s Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA
    Mol Cell Biol 25:3752-62. 2005
  3. ncbi request reprint Beta-cell growth: an unusual paradigm of organogenesis that is cyclin D2/Cdk4 dependent
    Jake A Kushner
    Children s Hospital of Philadelphia, Division of Endocrinology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Cell Cycle 5:234-7. 2006
  4. ncbi request reprint Phosphatase and tensin homolog regulation of islet growth and glucose homeostasis
    Jake A Kushner
    Division of Endocrinology, Children s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 280:39388-93. 2005
  5. pmc PERK is required in the adult pancreas and is essential for maintenance of glucose homeostasis
    Yan Gao
    The Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Mol Cell Biol 32:5129-39. 2012
  6. pmc Overexpression of hepatocyte nuclear factor-4α initiates cell cycle entry, but is not sufficient to promote β-cell expansion in human islets
    Sebastian Rieck
    Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, 12 126 Translational Research Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 5156, USA
    Mol Endocrinol 26:1590-602. 2012
  7. pmc Aging induces a distinct gene expression program in mouse islets
    Matthew M Rankin
    Division of Endocrinology and Diabetes, Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA USA
    Islets 2:345-52. 2010
  8. ncbi request reprint Very slow turnover of beta-cells in aged adult mice
    Monica Teta
    Division of Endocrinology, Children s Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA
    Diabetes 54:2557-67. 2005
  9. pmc β-Cells are not generated in pancreatic duct ligation-induced injury in adult mice
    Matthew M Rankin
    Division of Endocrinology and Diabetes, Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Diabetes 62:1634-45. 2013
  10. pmc Calcineurin signaling regulates human islet {beta}-cell survival
    Scott A Soleimanpour
    Division of Endocrinology, Department of Medicine and The Institute for Diabetes, Obesity, and Metabolism, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 285:40050-9. 2010

Collaborators

  • J Alan Diehl
  • Morris F White
  • Hui Zheng
  • Yan Gao
  • Serge Y Fuchs
  • Karen K Takane
  • Ewa Sicinska
  • Michael F Crutchlow
  • Sunmin Park
  • Piotr Sicinski
  • David Ludwig
  • Constantinos Koumenis
  • George King
  • Kevan C Herold
  • Neal Peachey
  • Maria A Ciemerych
  • Matthew M Rankin
  • Monica Teta
  • Simon Y Long
  • Daniel J Sartori
  • Christopher J Wilbur
  • Nilesh S Chitnis
  • Sebastian Rieck
  • Ali Naji
  • Chengyang Liu
  • Markus Schubert
  • Scott A Soleimanpour
  • Lu Mei He
  • Mark J Kiel
  • Vitaly Ablamunits
  • Alexey Podcheko
  • Janet Farhang-Fallah
  • Xianjin Yi
  • Carrie L Flint
  • Dorota B Pawlak
  • Deborah J Burks
  • Xueying Lin
  • Changhong Li
  • William T Pu
  • Hakon Hakonarson
  • Jonathan P Bradfield
  • Struan F A Grant
  • Emily J Shields
  • Kimberly Rak
  • Anne Granger
  • Zhaoyu Li
  • Nathalie M Fiaschi-Taesch
  • Brian Frederick
  • Nancy L Maas
  • Dariusz Pytel
  • Jia Zhang
  • Ekaterina Bobrovnikova-Marjon
  • Lewis A Chodosh
  • Andrew F Stewart
  • Klaus H Kaestner
  • Dhruv Pant
  • Jeffrey C Raum
  • Alana M Ferrari
  • David N Groff
  • Diva D De Leon
  • Doris A Stoffers
  • Lynn M Opare-Addo
  • Geneva M Stein
  • Shenghui He
  • Sara N Gentry
  • Rina Ashkenazi
  • Swaroop R Bommareddi
  • Andrew Lee
  • Nicole A Sherry
  • Maria Rozakis-Adcock
  • Trachette L Jackson
  • George Bikopoulos
  • Paul Northcott
  • Sean J Morrison
  • Matthew A Dow
  • Christopher Cahill
  • Izumi Suzuma
  • Rebecca L Leshan
  • Lynn M Wartschow
  • Kiyoshi Suzuma
  • Yedan Li
  • Fan Li
  • Akiko Taguchi
  • Gabriel Corfas
  • Xavier M Warot
  • Jing Ye
  • Carlos Rio
  • Derek P Brazil
  • Pieter Dikkes

Detail Information

Publications23

  1. pmc Pdx1 restores beta cell function in Irs2 knockout mice
    Jake A Kushner
    Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 109:1193-201. 2002
    ..Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY...
  2. pmc Cyclins D2 and D1 are essential for postnatal pancreatic beta-cell growth
    Jake A Kushner
    Division of Endocrinology, Children s Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA
    Mol Cell Biol 25:3752-62. 2005
    ..Thus, cyclins D2 and D1 were essential for beta-cell expansion in adult mice. Strategies to tightly regulate D-type cyclin activity in beta cells could prevent or cure diabetes...
  3. ncbi request reprint Beta-cell growth: an unusual paradigm of organogenesis that is cyclin D2/Cdk4 dependent
    Jake A Kushner
    Children s Hospital of Philadelphia, Division of Endocrinology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Cell Cycle 5:234-7. 2006
    ..This new paradigm of long-lived beta-cells challenges previous notions of rapid turnover of adult beta-cell mass. Thus, much remains to be learned in order to expand adult beta-cell mass in diabetes patients...
  4. ncbi request reprint Phosphatase and tensin homolog regulation of islet growth and glucose homeostasis
    Jake A Kushner
    Division of Endocrinology, Children s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 280:39388-93. 2005
    ..Thus, steps to enhance phosphatidylinositol 3-kinase signaling can promote beta-cell growth, function, and survival without the Irs2 branch of the insulin/insulin-like growth factor signaling cascade...
  5. pmc PERK is required in the adult pancreas and is essential for maintenance of glucose homeostasis
    Yan Gao
    The Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Mol Cell Biol 32:5129-39. 2012
    ..This work demonstrates that contrary to expectations, PERK is required for secretory homeostasis and β cell survival in adult mice...
  6. pmc Overexpression of hepatocyte nuclear factor-4α initiates cell cycle entry, but is not sufficient to promote β-cell expansion in human islets
    Sebastian Rieck
    Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, 12 126 Translational Research Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 5156, USA
    Mol Endocrinol 26:1590-602. 2012
    ..The DNA damage response is a barrier to efficient β-cell proliferation in vitro, and we suggest its evaluation in all attempts to stimulate β-cell replication as an approach to diabetes treatment...
  7. pmc Aging induces a distinct gene expression program in mouse islets
    Matthew M Rankin
    Division of Endocrinology and Diabetes, Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA USA
    Islets 2:345-52. 2010
    ..Taken together, our results reveal that aged islets exhibit a unique gene expression signature that could contribute to the limited regenerative capacity of mature β-cells...
  8. ncbi request reprint Very slow turnover of beta-cells in aged adult mice
    Monica Teta
    Division of Endocrinology, Children s Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA
    Diabetes 54:2557-67. 2005
    ..Although some pancreatic components acquired BrdU label in a linear fashion, only 1 in approximately 1,400 adult beta-cells were found to undergo replication per day. We conclude that adult beta-cells are very long lived...
  9. pmc β-Cells are not generated in pancreatic duct ligation-induced injury in adult mice
    Matthew M Rankin
    Division of Endocrinology and Diabetes, Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Diabetes 62:1634-45. 2013
    ..Thus, we conclude that β-cells are not generated in injured adult mouse pancreas...
  10. pmc Calcineurin signaling regulates human islet {beta}-cell survival
    Scott A Soleimanpour
    Division of Endocrinology, Department of Medicine and The Institute for Diabetes, Obesity, and Metabolism, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 285:40050-9. 2010
    ..These findings reveal calcineurin as a regulator of human β-cell survival in part through regulation of Irs2, with implications for the pathogenesis and treatment of diabetes following organ transplantation...
  11. pmc Cyclin D2 protein stability is regulated in pancreatic beta-cells
    Lu Mei He
    Division of Endocrinology and Diabetes, Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Mol Endocrinol 23:1865-75. 2009
    ....
  12. pmc GATA Factors Promote ER Integrity and β-Cell Survival and Contribute to Type 1 Diabetes Risk
    Daniel J Sartori
    Division of Endocrinology and Diabetes D J S, C J W, S Y L, M M R, C L, Children s Hospital of Philadelphia, Department of Pediatrics H H, S F A G, Perelman School of Medicine, and Center for Applied Genomics J P B, H H, S F A G, Abramson Research Center, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104 Department of Cardiology W T P, Children s Hospital, Boston, Harvard Medical School, Boston, Massachusetts 02115 Section of Pediatric Diabetes and Endocrinology J A K, Baylor College of Medicine, Houston, Texas 77030 and Diabetes and Endocrinology Service J A K, Texas Children s Hospital, Houston, Texas 77030
    Mol Endocrinol 28:28-39. 2014
    ..We conclude that GATA factors have important but nonessential roles to promote ER integrity and β-cell survival in a tissue-specific manner and that GATA factors likely contribute to type 1 diabetes mellitus pathogenesis. ..
  13. pmc miR-211 is a prosurvival microRNA that regulates chop expression in a PERK-dependent manner
    Nilesh S Chitnis
    The Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Cell 48:353-64. 2012
    ..Our data suggest a model in which PERK-dependent miR-211 induction prevents premature chop accumulation and thereby provides a window of opportunity for the cell to re-establish homeostasis prior to apoptotic commitment...
  14. ncbi request reprint Growth and regeneration of adult beta cells does not involve specialized progenitors
    Monica Teta
    Division of Endocrinology, Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Dev Cell 12:817-26. 2007
    ..Our approach provides unbiased resolution of previously inaccessible developmental niches and can elucidate lineage mechanisms without candidate markers...
  15. pmc Adaptive beta-cell proliferation is severely restricted with advanced age
    Matthew M Rankin
    Division of Endocrinology and Diabetes, The Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Diabetes 58:1365-72. 2009
    ..beta-Cell proliferation can be acutely stimulated by a variety of stimuli in young rodents. However, it is unknown whether this adaptive beta-cell regeneration capacity is retained into old age...
  16. pmc Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetes
    Xueying Lin
    Howard Hughes Medical Institute Children s Hospital, Division of Endocrinology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 114:908-16. 2004
    ..Thus, Irs2 signaling promotes regeneration of adult beta cells and central control of nutrient homeostasis, which can prevent obesity and diabetes in mice...
  17. ncbi request reprint Islet-sparing effects of protein tyrosine phosphatase-1b deficiency delays onset of diabetes in IRS2 knockout mice
    Jake A Kushner
    Howard Hughes Medical Institute, Joslin Diabetes Center, and Division of Endocrinology, Children s Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA
    Diabetes 53:61-6. 2004
    ..Our studies demonstrate a novel role for Ptp1b in regulating beta-cell homeostasis and indicate that Ptp1b deficiency can partially compensate for lack of Irs2...
  18. ncbi request reprint Effects of dietary glycaemic index on adiposity, glucose homoeostasis, and plasma lipids in animals
    Dorota B Pawlak
    Department of Medicine, Children s Hospital, Boston, MA, USA
    Lancet 364:778-85. 2004
    ..This study examined the independent effects of GI in animals...
  19. ncbi request reprint Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation
    Markus Schubert
    Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Neurosci 23:7084-92. 2003
    ..Thus, dysregulation of the Irs2 branch of the insulin-Igf-signaling cascade reveals a molecular link between diabetes and neurodegenerative disease...
  20. ncbi request reprint Insulin receptor substrate 2 is essential for maturation and survival of photoreceptor cells
    Xianjin Yi
    Howard Hughes Medical Institute, Children s Hospital Boston, Boston, Massachusetts 02115, USA
    J Neurosci 25:1240-8. 2005
    ....
  21. ncbi request reprint Autoimmunity and beta cell regeneration in mouse and human type 1 diabetes: the peace is not enough
    Vitaly Ablamunits
    Section of Immunobiology, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
    Ann N Y Acad Sci 1103:19-32. 2007
    ..Additional therapeutic modalities capable of stimulating beta cell regeneration in the absence of active autoimmune destruction are urgently needed...
  22. pmc Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU
    Mark J Kiel
    Howard Hughes Medical Institute, Life Sciences Institute, Department of Internal Medicine, and Centre for Stem Cell Biology, University of Michigan, Ann Arbor, Michigan 48109 2216, USA
    Nature 449:238-42. 2007
    ..Thus, HSCs cannot be identified on the basis of BrdU-label retention and do not retain older DNA strands during division, indicating that these are not general properties of stem cells...
  23. pmc Identification of a WD40 repeat-containing isoform of PHIP as a novel regulator of beta-cell growth and survival
    Alexey Podcheko
    Department of Laboratory Medicine and Pathobiology, 1 King s College Circle, Room 6238, University of Toronto, Toronto, Canada M5S 1A8
    Mol Cell Biol 27:6484-96. 2007
    ..We suggest that PHIP1 may be involved in the induction of long-term gene expression programs to promote beta-cell mitogenesis and survival...