Roland W. Stein, Ph.D.


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Faculty Appointments
Professor of Molecular Physiology and Biophysics Professor of Cell and Developmental BiologyMark Collie Chair in Diabetes Resesarch
Ph.D., Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, New YorkM.A., Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, New YorkB.A., Biochemistry, University of California, Los Angeles, California
Office Address
702 Light Hall
TN 0615
Research Description
Until recently, little detailed information was known about the factors controlling pancreas development and islet beta cell function. However, our understanding has increased greatly with the identification and molecular characterization of the islet-enriched MafA, MafB, and PDX-1 transcription factors. Gene knockouts performed on these and other pancreas-enriched factors are helping to elucidate the events influencing pancreatic morphogenesis. Because of their unique expression pattern and fundamental significance to beta cells, work here is focused on defining the transcription factors involved in controlling the expression of Pdx-1 and MafA. In addition, we are examining how transcriptional factors influence beta cell formation and function. Our recent results indicate that MafA and MafB strongly impact whether a cell becomes a producer in the islet of the insulin (beta) or glucagon (alpha) hormone. Both animal and cell culture models are used in these studies, with comprehensive and diverse methods from Cre/loxP conditional gene inactivation to mass spectrometry involved in addressing our experimental questions.

Understanding the mechanisms involved in controlling of pancreatic islet beta-cell specific transcription will likely lead to the development of therapeutic approaches that will prevent, correct, or at least delay the decline in beta cell function observed in diabetics. In fact, considerable efforts are focused on trying to develop an unlimited source of insulin-producing beta-like cells from adult and embryonic stem cells, as a consequence of success in reversing type 1 diabetes by islet transplantation. We believe that long-term success in this endeavor will require a fundamental understanding of the regulatory factors that are required for controlling the specialized genetic programs associated with beta cells. Our hope is that successful completion of our proposed studies will provide information important for generating acceptable islet-like cells for therapeutic treatment.

The beta cell biology community here is also very interactive and supportive, with eight groups meeting weekly to discuss their most recent findings. This gives students, post-docs, and faculty a routine opportunity to obtain input from a group of experts.
Research Keywords
Focused on defining the transcription factors involved in controlling the expression of Pdx-1 and MafA. In addition, we are examining how transcriptional factors influence beta cell formation and function.
Wiebe PO, Kormish JD, Roper VT, Fujitani Y, Alston NI, Zaret KS, Wright CV, Stein RW, Gannon M. Ptf1a binds to and activates area III, a highly conserved region of the Pdx1 promoter that mediates early pancreas-wide Pdx1 expression. Mol. Cell. Biol [print-electronic]. 2007 Jun; 27(11): 4093-104. PMID: 17403901, PMCID: PMC1900007, PII: MCB.01978-06, DOI: 10.1128/MCB.01978-06, ISSN: 0270-7306.

Artner, I and Stein, R. Insulin Gene Transcription: The Factors involved in Cell-type-Specific and Glucose-Regulated Expression in Islet beta Cells are also Essential during Pancreatic Development. 2007; ((Review Article- in press)).

Artner, I., Blanchi, B., Raum, J.C., Guo, M., Kaneko, T., Cordes, S., Sieweke, M., and Stein, R.. MafB is required for islet beta cell maturation. Proc Natl Acad Sci U S A. 2007; 104(10):3853-8.

Oetjen E., Blume R., Cierny I., Schlag C., Kutschenko A., Kratzner R., Stein R., Knepel W.. Nhibition of MafA transcriptional activity and human insulin gene transcription by interleukin-1beta and mitogen-activated protein kinase kinase kinase in pancreatic islet beta cells. Diabetologia. 2007; in press.

Wiebe PO, Kormish JD, Roper VT, Fujitani Y, Alston NI, Zaret KS, Wright CV, Stein RW, Gannon M.. Ptf1a binds to and activates area III, a highly conserved region of the Pdx1 promoter that mediates early pancreas-wide Pdx1 expression. Mol. Cell. Biol. 2007; 27:4093-104.

Boyer DF, Fujitani Y, Gannon M, Powers AC, Stein RW, Wright CV. Complementation rescue of Pdx1 null phenotype demonstrates distinct roles of proximal and distal cis-regulatory sequences in pancreatic and duodenal expression. Dev. Biol [print-electronic]. 2006 Oct 10/15/2006; 298(2): 616-31. PMID: 16962573, PII: S0012-1606(06)01026-8, DOI: 10.1016/j.ydbio.2006.07.020, ISSN: 0012-1606.

Fujitani Y, Fujitani S, Boyer DF, Gannon M, Kawaguchi Y, Ray M, Shiota M, Stein RW, Magnuson MA, Wright CV. Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation. Genes Dev. 2006 Jan 1/15/2006; 20(2): 253-66. PMID: 16418487, PMCID: PMC1356115, PII: 20/2/253, DOI: 10.1101/gad.1360106, ISSN: 0890-9369.

Artner, I., Lelay, J., Hang, Y., Elgazhi, L., Schisler, JC., Henderson, E., Sosa-Pineda, B., and Stein, R.. MafB: A Transcription Factor of the Glucagon Gene in Islet alpha Cells is also Expressed in Alpha Cell Progenitors. Diabetes. 2006; 55:297-304.

Le Lay, J. and and Stein, R.. Involvement of PDX-1 in Activation of Human Insulin Gene Transcription. J. of Endocrinology. 2006; 188(2):287-94.

Poitout, V., Hagman. D., Stein, R., Artner, I., Robertson, R.P., and Harmon, J.S.. Regulation of the insulin gene by glucose and fatty acids. J. Nutr. 2006; 136:873-876: (Review Article).

Ueki, K., Okada, T., Dahlren, G.M., Peters, J.L., Shacman, J.G., Zhang, M., Artner, I., Satin, L.S., Stein, R., Kennedy, R.T., Kahn, C.R., and Kulkarni, R.N.. Total Insulin/IGF-1 Resistance in Pancreatic Beta-Cells causes Overt Diabetes. Nature Med. 2006; 38:583-588.

Boyer DF, Fujitani Y, Gannon M, Powers AC, Stein RW, Wright CV.. Complementation rescue of Pdx1 null phenotype demonstrates distinct roles of proximal and distal cis-regulatory sequences in pancreatic and duodenal expression. Dev. Biol. 2006; 298:616-631.

Tweedie, E., Artner, I, Crawford, L, Poffenberger, G, Thorens, G, Stein, R, Powers, A, and Gannon, M. Maintenance of Hnf6 in postnatal islets impairs terminal differentiation and function of beta cells. Diabetes. 2006; 55:3264-3270.

Raum, J. Gerrish, K., Henderson, E., Guo, M., and Stein, R... Islet Beta-Cell Specific Expression of the MafA Transcription Factor is Regulated by FoxA2, Nkx2.2 and PDX-1 Binding to Conserved -8118 to -7748 Sequences. Mol. Cell. Biol. 2006; 26(15):5735-43.

Zhao L, Guo M, Matsuoka TA, Hagman DK, Parazzoli SD, Poitout V, Stein R. The islet beta cell-enriched MafA activator is a key regulator of insulin gene transcription. J. Biol. Chem [print-electronic]. 2005 Mar 3/25/2005; 280(12): 11887-94. PMID: 15665000, PII: M409475200, DOI: 10.1074/jbc.M409475200, ISSN: 0021-9258.

Harmon, J.S., Stein, R. and Robertson, R.P.. Oxidative stress-mediated, post-translational loss of MafA protein as a contributing mechanism to loss of insulin gene expression in glucotoxic beta cells. J. Biol. Chem. 2005; 280:11107-11113.

Van Velkinburgh, J.C., Samaras, S., Gerrish, K., Artner, I., and Stein, R.. Interactions between Areas I and II direct pdx-1 expression specifically to islet cell types of the mature and developing pancreas. J. Biol. Chem. 2005; 280:38438-44.

Kitamura, Y., Kitamura, T., Kruse, J. -P., Raum, J., Stein, R., Wei, G, and Accili, D.. Dual regulation of FoxO1 activity protects against pancreatic beta cell failure through NeuroD and MafA induction. Cell Metabolism. 2005; 2:153-163.

Le Lay J, Matsuoka TA, Henderson E, Stein R. Identification of a novel PDX-1 binding site in the human insulin gene enhancer. J. Biol. Chem [print-electronic]. 2004 May 5/21/2004; 279(21): 22228-35. PMID: 15028719, PII: M312673200, DOI: 10.1074/jbc.M312673200, ISSN: 0021-9258.

Qiu Y, Guo M, Huang S, Stein R. Acetylation of the BETA2 transcription factor by p300-associated factor is important in insulin gene expression. J. Biol. Chem [print-electronic]. 2004 Mar 3/12/2004; 279(11): 9796-802. PMID: 14701848, PII: M307577200, DOI: 10.1074/jbc.M307577200, ISSN: 0021-9258.

Matsuoka TA, Artner I, Henderson E, Means A, Sander M, Stein R. The MafA transcription factor appears to be responsible for tissue-specific expression of insulin. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2004 Mar 3/2/2004; 101(9): 2930-3. PMID: 14973194, PMCID: PMC365722, PII: 0306233101, DOI: 10.1073/pnas.0306233101, ISSN: 0027-8424.

Gerrish K, Van Velkinburgh JC, Stein R. Conserved transcriptional regulatory domains of the pdx-1 gene. Mol. Endocrinol [print-electronic]. 2004 Mar; 18(3): 533-48. PMID: 14701942, PII: me.2003-0371, DOI: 10.1210/me.2003-0371, ISSN: 0888-8809.

Review: Poitout, V., Stein, R., and Rhodes, C.J.. Insulin gene expression and biosynthesis. International Textbook of Diabetes Mellitus. 2004; Volume III, E. Ferrannini, P. Zimmet, R. DeFronzo and H. Keen. Eds. (NYC, New York; John Wiley & Sons).

Cockburn, B.N., Bermano, G., Boodram, L.-L., Telllucksingh, S., Tsuchiya, T., Mahabir, D., Allan, A.B., Stein, R., Docherty, K., and Bell, G.I.. Identification and functional characterization of a novel diabetes-associated mutation (E224K) in the IPF-1 (MODY4) gene in an Indo-Trinidadian family. J. Clin. Endo. and Metab. 2004; 89: 971-8.

Matsuoka TA, Zhao L, Artner I, Jarrett HW, Friedman D, Means A, Stein R. Members of the large Maf transcription family regulate insulin gene transcription in islet beta cells. Mol. Cell. Biol. 2003 Sep; 23(17): 6049-62. PMID: 12917329, PMCID: PMC180917, ISSN: 0270-7306.

Griffin D, Penberthy WT, Lum H, Stein RW, Taylor WL. Isolation of the B3 transcription factor of the Xenopus TFIIIA gene. Gene. 2003 Aug 8/14/2003; 313: 179-88. PMID: 12957389, PII: S0378111903006784, ISSN: 0378-1119.

Martin CC, Svitek CA, Oeser JK, Henderson E, Stein R, O'Brien RM. Upstream stimulatory factor (USF) and neurogenic differentiation/beta-cell E box transactivator 2 (NeuroD/BETA2) contribute to islet-specific glucose-6-phosphatase catalytic-subunit-related protein (IGRP) gene expression. Biochem. J. 2003 May 5/1/2003; 371(Pt 3): 675-86. PMID: 12540293, PMCID: PMC1223330, PII: BJ20021585, DOI: 10.1042/BJ20021585, ISSN: 0264-6021.

Samaras SE, Zhao L, Means A, Henderson E, Matsuoka TA, Stein R. The islet beta cell-enriched RIPE3b1/Maf transcription factor regulates pdx-1 expression. J. Biol. Chem [print-electronic]. 2003 Apr 4/4/2003; 278(14): 12263-70. PMID: 12551916, PII: M210801200, DOI: 10.1074/jbc.M210801200, ISSN: 0021-9258.

Cissell MA, Zhao L, Sussel L, Henderson E, Stein R. Transcription factor occupancy of the insulin gene in vivo. Evidence for direct regulation by Nkx2.2. J. Biol. Chem [print-electronic]. 2003 Jan 1/10/2003; 278(2): 751-6. PMID: 12426319, PII: M205905200, DOI: 10.1074/jbc.M205905200, ISSN: 0021-9258.

Moates, J.M., Nanda, S., Cissell, M., and Stein, R.. The BETA2 transcription factor binds to and activates expression of the glucokinase gene in beta cells. Diabetes. 2003; 52: 403-8.

Samaras SE, Cissell MA, Gerrish K, Wright CV, Gannon M, Stein R. Conserved sequences in a tissue-specific regulatory region of the pdx-1 gene mediate transcription in Pancreatic beta cells: role for hepatocyte nuclear factor 3 beta and Pax6. Mol. Cell. Biol. 2002 Jul; 22(13): 4702-13. PMID: 12052878, PMCID: PMC133887, ISSN: 0270-7306.

Qiu Y, Guo M, Huang S, Stein R. Insulin gene transcription is mediated by interactions between the p300 coactivator and PDX-1, BETA2, and E47. Mol. Cell. Biol. 2002 Jan; 22(2): 412-20. PMID: 11756538, PMCID: PMC139753, ISSN: 0270-7306.

Shih, D.Q., Heimesaat, M.E., Kuwajima, S., Stein, R., Wright, C.V.E., Stoffel, M. Defects in Pancreatic Beta-Cell function in Mice with Combined Heterozygous Mutations in Pdx-1, Hnf-1 alpha and Hnf-3 beta. Proc. Natl. Acad. Sci. 2002; 99: 3818-23.

Petersen, H.V., Jensen, J.N., Stein, R., and Serup, P. Glucose induced MAPK signaling influences NeuroD1-mediated activation and nuclear localization. FEBS Letters. 2002; 528: 1-3.

Gerrish K, Cissell MA, Stein R. The role of hepatic nuclear factor 1 alpha and PDX-1 in transcriptional regulation of the pdx-1 gene. J. Biol. Chem [print-electronic]. 2001 Dec 12/21/2001; 276(51): 47775-84. PMID: 11590182, PII: M109244200, DOI: 10.1074/jbc.M109244200, ISSN: 0021-9258.

Matsuoka T, Zhao L, Stein R. The DNA binding activity of the RIPE3b1 transcription factor of insulin appears to be influenced by tyrosine phosphorylation. J. Biol. Chem [print-electronic]. 2001 Jun 6/22/2001; 276(25): 22071-6. PMID: 11309378, PII: M010321200, DOI: 10.1074/jbc.M010321200, ISSN: 0021-9258.

Review: Stein, R. Insulin gene transcription: the factors involved in cell-type-specific and glucose-regulated expression in islet beta cells are also essential during pancreatic development. Handbook of Physiology. Section 7: The Endocrine System. 2001; II((A. Cherrington and J. Jefferson. Eds. (Washington, D.C. American Physiology Society)): 25-78.

Peshavaria M, Cissell MA, Henderson E, Petersen HV, Stein R. The PDX-1 activation domain provides specific functions necessary for transcriptional stimulation in pancreatic beta-cells. Mol. Endocrinol. 2000 Dec; 14(12): 1907-17. PMID: 11117522, DOI: 10.1210/mend.14.12.0563, ISSN: 0888-8809.

Zhao L, Cissell MA, Henderson E, Colbran R, Stein R. The RIPE3b1 activator of the insulin gene is composed of a protein(s) of approximately 43 kDa, whose DNA binding activity is inhibited by protein phosphatase treatment. J. Biol. Chem. 2000 Apr 4/7/2000; 275(14): 10532-7. PMID: 10744746, ISSN: 0021-9258.

Gerrish K, Gannon M, Shih D, Henderson E, Stoffel M, Wright CV, Stein R. Pancreatic beta cell-specific transcription of the pdx-1 gene. The role of conserved upstream control regions and their hepatic nuclear factor 3beta sites. J. Biol. Chem. 2000 Feb 2/4/2000; 275(5): 3485-92. PMID: 10652343, ISSN: 0021-9258.

Review: Gerrish, K., Samaras, S., Cissell, M.A., Wright, C.V.E., and Stein, R. Regulation of pdx-1 gene expression. Review for Molecular Basis of Pancreatic Development and Function. Editors: M.A. Hussein, C.P. Miller, and J.F. Habener Kluwer Academic Publishers, Nowell, MA. 2000; 251-63.

Review: Gannon, M, Gerrish, K., Stein, R., and Wright, C.V.E. Role of pdx-1 in pancreas development. Review for Frontiers in Diabetes: Molecular pathogenesis of MODYs. Editors: F.M. Matschinsky and M.A. Magnuson, S. Karger Publishers. 2000; 166-80.

Huang S, Qiu Y, Stein RW, Brandt SJ. P300 functions as a transcriptional coactivator for the TAL1/SCL oncoprotein. Oncogene. 1999 Sep 9/2/1999; 18(35): 4958-67. PMID: 10490830, DOI: 10.1038/sj.onc.1202889, ISSN: 0950-9232.

Sharma A, Moore M, Marcora E, Lee JE, Qiu Y, Samaras S, Stein R. The NeuroD1/BETA2 sequences essential for insulin gene transcription colocalize with those necessary for neurogenesis and p300/CREB binding protein binding. Mol. Cell. Biol. 1999 Jan; 19(1): 704-13. PMID: 9858593, PMCID: PMC83927, ISSN: 0270-7306.

Qiu Y, Sharma A, Stein R. P300 mediates transcriptional stimulation by the basic helix-loop-helix activators of the insulin gene. Mol. Cell. Biol. 1998 May; 18(5): 2957-64. PMID: 9566915, PMCID: PMC110675, ISSN: 0270-7306.

Petersen, H.V., Peshavaria, M., Pedersen, A.A., Philippe, J., Stein, R., Madsen, O., and Serup, P. "Glucose Stimulates the Activation Domain Potential of the PDX-1 Homeodomain Transcription Factor.". FEBS Lett. 1998; 431: 362-6.

Sharma A, Henderson E, Gamer L, Zhuang Y, Stein R. Analysis of the role of E2A-encoded proteins in insulin gene transcription. Mol. Endocrinol. 1997 Oct; 11(11): 1608-17. PMID: 9328343, DOI: 10.1210/mend.11.11.0004, ISSN: 0888-8809.

Wu KL, Gannon M, Peshavaria M, Offield MF, Henderson E, Ray M, Marks A, Gamer LW, Wright CV, Stein R. Hepatocyte nuclear factor 3beta is involved in pancreatic beta-cell-specific transcription of the pdx-1 gene. Mol. Cell. Biol. 1997 Oct; 17(10): 6002-13. PMID: 9315659, PMCID: PMC232449, ISSN: 0270-7306.

Peshavaria M, Henderson E, Sharma A, Wright CV, Stein R. Functional characterization of the transactivation properties of the PDX-1 homeodomain protein. Mol. Cell. Biol. 1997 Jul; 17(7): 3987-96. PMID: 9199333, PMCID: PMC232251, ISSN: 0270-7306.

Fernandes, A., King, L.C., Guz, Y., Stein, R., Wright, C.V.E., and Teitelman, G. "Differentiation of New Insulin Producing Cells is Induced by Injury in Adult Pancreatic Islets.". Endocrinology. 1997; 138: 1750-62.

Carty, M.D., Lillquist, J.S., Peshavaria, M., Stein, R., and Soeller, W.C. "Identification of Cis- and Trans-active Factors Regulating Islet Amyloid Polypeptide Expression in Pancreatic b cells.". J. Biol. Chem. 1997; 272: 11986-93.

Peshavaria, M. and Stein, R. "PDX-1: An Activator of Genes Involved in Pancreatic Development and Islet Gene Expression.". Review for Pancreas Growth and Regeneration, Editor: Nora Sarvetnick, Molecular Biology Intelligence Unit, Publishers: Karger Landes Systems. 1997; 96.

Offield MF, Jetton TL, Labosky PA, Ray M, Stein RW, Magnuson MA, Hogan BL, Wright CV. PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development. 1996 Mar; 122(3): 983-95. PMID: 8631275, ISSN: 0950-1991.

Sharma A, Fusco-DeMane D, Henderson E, Efrat S, Stein R. The role of the insulin control element and RIPE3b1 activators in glucose-stimulated transcription of the insulin gene. Mol. Endocrinol. 1995 Nov; 9(11): 1468-76. PMID: 8584024, DOI: 10.1210/mend.9.11.8584024, ISSN: 0888-8809.

Sharma A, Olson LK, Robertson RP, Stein R. The reduction of insulin gene transcription in HIT-T15 beta cells chronically exposed to high glucose concentration is associated with the loss of RIPE3b1 and STF-1 transcription factor expression. Mol. Endocrinol. 1995 Sep; 9(9): 1127-34. PMID: 7491105, DOI: 10.1210/mend.9.9.7491105, ISSN: 0888-8809.

Robinson GL, Henderson E, Massari ME, Murre C, Stein R. C-jun inhibits insulin control element-mediated transcription by affecting the transactivation potential of the E2A gene products. Mol. Cell. Biol. 1995 Mar; 15(3): 1398-404. PMID: 7862133, PMCID: PMC230364, ISSN: 0270-7306.

Guz, Y., Montminy, M.R., Stein, R., Gamer, L.W., Wright, C.V.E., and Teitelman, G. "Expression of the STF-1 Homeobox Protein Identifies Common Precursors for Endocrine and Exocrine Pancreatic Cells.". Development. 1995; 121: 11-8.

Stoffel, M., Stein, R., Wright, C.V.E., Espinosa, R. III, Le Beau, M.M., and Bell, G.I. "Localization of Human Homeodomain Transcription Factor Insulin Promoter Factor 1 (IPF1) to Chromosome Band 13q12.1". Genomics. 1995; 28: 125-6.

Olson, L.K., Sharma, A., Wright, C.V.E., Towle, H.C., Robertson, R.P., and Stein, R. "Reduction of Insulin Gene Transcription in HIT-T15 b cells Chronically Exposed to a Supraphysiological Glucose Concentration is Associated with Loss of STF-1 Transcription Factor Expression.". Proc. Natl. Acad. Sci. 1995; 92: 9127-31.

Robinson GL, Cordle SR, Henderson E, Weil PA, Teitelman G, Stein R. Isolation and characterization of a novel transcription factor that binds to and activates insulin control element-mediated expression. Mol. Cell. Biol. 1994 Oct; 14(10): 6704-14. PMID: 7935390, PMCID: PMC359201, ISSN: 0270-7306.

Peshavaria M, Gamer L, Henderson E, Teitelman G, Wright CV, Stein R. XIHbox 8, an endoderm-specific Xenopus homeodomain protein, is closely related to a mammalian insulin gene transcription factor. Mol. Endocrinol. 1994 Jun; 8(6): 806-16. PMID: 7935494, DOI: 10.1210/mend.8.6.7935494, ISSN: 0888-8809.

Sharma A, Stein R. Glucose-induced transcription of the insulin gene is mediated by factors required for beta-cell-type-specific expression. Mol. Cell. Biol. 1994 Feb; 14(2): 871-9. PMID: 8289826, PMCID: PMC358441, ISSN: 0270-7306.

Stein R, Henderson E, Cordle SR. Analysis of an insulin gene transcription control element. Positive and negative regulation appears to be mediated by different element sequences. FEBS Lett. 1994 Jan 1/31/1994; 338(2): 187-90. PMID: 8307179, PII: 0014-5793(94)80362-5, ISSN: 0014-5793.

Robinson GL, Peshavaria M, Henderson E, Shieh SY, Tsai MJ, Teitelman G, Stein R. Expression of the trans-active factors that stimulate insulin control element-mediated activity appear to precede insulin gene transcription. J. Biol. Chem. 1994 Jan 1/28/1994; 269(4): 2452-60. PMID: 8300572, ISSN: 0021-9258.

Henderson E, Stein R. C-jun inhibits transcriptional activation by the insulin enhancer, and the insulin control element is the target of control. Mol. Cell. Biol. 1994 Jan; 14(1): 655-62. PMID: 8264634, PMCID: PMC358415, ISSN: 0270-7306.

Hicks BA, Stein R, Efrat S, Grant S, Hanahan D, Demetriou AA. Transplantation of beta cells from transgenic mice into nude athymic diabetic rats restores glucose regulation. Diabetes Res. Clin. Pract. 1991 Dec; 14(3): 157-64. PMID: 1778108, ISSN: 0168-8227.

Pietenpol JA, Münger K, Howley PM, Stein RW, Moses HL. Factor-binding element in the human c-myc promoter involved in transcriptional regulation by transforming growth factor beta 1 and by the retinoblastoma gene product. Proc. Natl. Acad. Sci. U.S.A. 1991 Nov 11/15/1991; 88(22): 10227-31. PMID: 1946442, PMCID: PMC52901, ISSN: 0027-8424.

Cordle SR, Whelan J, Henderson E, Masuoka H, Weil PA, Stein R. Insulin gene expression in nonexpressing cells appears to be regulated by multiple distinct negative-acting control elements. Mol. Cell. Biol. 1991 May; 11(5): 2881-6. PMID: 2017182, PMCID: PMC360077, ISSN: 0270-7306.

Cordle SR, Henderson E, Masuoka H, Weil PA, Stein R. Pancreatic beta-cell-type-specific transcription of the insulin gene is mediated by basic helix-loop-helix DNA-binding proteins. Mol. Cell. Biol. 1991 Mar; 11(3): 1734-8. PMID: 1996119, PMCID: PMC369485, ISSN: 0270-7306.

Stein RW, Corrigan M, Yaciuk P, Whelan J, Moran E. Analysis of E1A-mediated growth regulation functions: binding of the 300-kilodalton cellular product correlates with E1A enhancer repression function and DNA synthesis-inducing activity. J. Virol. 1990 Sep; 64(9): 4421-7. PMID: 2143544, PMCID: PMC247911, ISSN: 0022-538X.

Pietenpol JA, Stein RW, Moran E, Yaciuk P, Schlegel R, Lyons RM, Pittelkow MR, Münger K, Howley PM, Moses HL. TGF-beta 1 inhibition of c-myc transcription and growth in keratinocytes is abrogated by viral transforming proteins with pRB binding domains. Cell. 1990 Jun 6/1/1990; 61(5): 777-85. PMID: 2140528, PII: 0092-8674(90)90188-K, ISSN: 0092-8674.

Pietenpol JA, Holt JT, Stein RW, Moses HL. Transforming growth factor beta 1 suppression of c-myc gene transcription: role in inhibition of keratinocyte proliferation. Proc. Natl. Acad. Sci. U.S.A. 1990 May; 87(10): 3758-62. PMID: 2187192, PMCID: PMC53982, ISSN: 0027-8424.

Whelan J, Cordle SR, Henderson E, Weil PA, Stein R. Identification of a pancreatic beta-cell insulin gene transcription factor that binds to and appears to activate cell-type-specific expression: its possible relationship to other cellular factors that bind to a common insulin gene sequence. Mol. Cell. Biol. 1990 Apr; 10(4): 1564-72. PMID: 2181278, PMCID: PMC362261, ISSN: 0270-7306.

Stein RW, Whelan J. Insulin gene enhancer activity is inhibited by adenovirus 5 E1a gene products. Mol. Cell. Biol. 1989 Oct; 9(10): 4531-4. PMID: 2531280, PMCID: PMC362538, ISSN: 0270-7306.

Whelan J, Poon D, Weil PA, Stein R. Pancreatic beta-cell-type-specific expression of the rat insulin II gene is controlled by positive and negative cellular transcriptional elements. Mol. Cell. Biol. 1989 Aug; 9(8): 3253-9. PMID: 2552288, PMCID: PMC362369, ISSN: 0270-7306.

Available Postdoctoral Position Details
Posted Position

Applications are invited for a postdoctoral position to study the mechanisms that regulate human pancreatic islet alpha and beta cell function. Investigations will involve examining how both normal and pathophysiological conditions impact islet cells, including those associated with Type 1 and Type 2 diabetes. Analysis of candidate effector function will be conducted in model systems, for example using mouse in vivo models and human cell lines. Cutting edge approaches in RNA gene expression, epigenetics, cell imaging, and mass spectrometry based proteomics will be utilized.

Refer to lab website for background information:

Successful applicants will work with a very successful team of postdoctoral fellows and senior technicians, and should have a proven ability to perform basic research in cell biology, biochemistry and/or molecular biology.

To apply, please send (1) a cover letter, (2) CV, (3) statement of research interests/experiences, and (4) names and contact information for three references to Roland Stein (

12/3/2010 Postdoctoral Research Fellow Position Available Immediately

Term: at least 2 years

Salary and Benefits: Aprox.$50,000 plus benefits

Project(s): see research description

Please send CV to:
Roland Stein, Ph.D.

Molecular Physiology & Biophysics

702 Light Hall

Nashville, TN 37232-0615