Klaus Kaestner, Ph.D.

Professor
University of Pennsylvania
Department of Genetics

12-126 SCTR, 3400 Civic Center Blvd
Philadelphia, PA 19104-6145
USA

p. 215-898-8759
f. 215-573-5892
· email
· website

Klaus Kaestner, Ph.D. - Investigator Profile

We are interested in the identification and analysis of the regulatory, or Master, genes that control the development and function of the pancreas. These genes often encode for transcription factors that control the activity of whole sets of target genes in a given tissue. We are utilizing the mouse as a model system for two reasons: its relevance as a model for human disease and its accessibility to precise alterations of the genome through gene targeting. We are also heavily invested in studying the epigenome of the mammalian endocrine pancreas, and how this relates to the decreased function of beta-cells in type 2 diabetes and aging.

Scientific Interests/Keywords

Epigenomics of beta-cells; beta-cell proliferation; transcriptional regulation of pancreas development

Publication	Citation
21070761	Ghaleb AM, McConnell BB, Kaestner KH, Yang VW Altered intestinal epithelial homeostasis in mice with intestine-specific deletion of the Krüppel-like factor 4 gene. (2010) Dev Biol : (Added 2011-01-07 10:34:55.62106)
20880840	Haeusler RA, Kaestner KH, Accili D FoxOs function synergistically to promote glucose production. (2010) J Biol Chem 285: 35245-8 (Added 2011-01-07 10:34:55.731675)
20843784	Gao Y, Schug J, McKenna LB, Le Lay J, Kaestner KH, Greenbaum LE Tissue-specific regulation of mouse MicroRNA genes in endoderm-derived tissues. (2010) Nucleic Acids Res : (Added 2011-01-07 10:34:55.740849)
20659473	McKenna LB, Schug J, Vourekas A, McKenna JB, Bramswig NC, Friedman JR, Kaestner KH MicroRNAs control intestinal epithelial differentiation, architecture, and barrier function. (2010) Gastroenterology 139: 1654-64, 1664.e1 (Added 2011-01-07 10:34:55.749767)
20640398	Zhao J, Schug J, Li M, Kaestner KH, Grant SF Disease-associated loci are significantly over-represented among genes bound by transcription factor 7-like 2 (TCF7L2) in vivo. (2010) Diabetologia 53: 2340-6 (Added 2011-01-07 10:34:55.757881)
20591647	Kaestner KH The FoxA factors in organogenesis and differentiation. (2010) Curr Opin Genet Dev 20: 527-32 (Added 2011-01-07 10:34:55.772467)
20551175	Gao N, Kaestner KH Cdx2 regulates endo-lysosomal function and epithelial cell polarity. (2010) Genes Dev 24: 1295-305 (Added 2011-01-07 10:34:55.781532)
20534694	Gao N, Le Lay J, Qin W, Doliba N, Schug J, Fox AJ, Smirnova O, Matschinsky FM, Kaestner KH Foxa1 and Foxa2 maintain the metabolic and secretory features of the mature beta-cell. (2010) Mol Endocrinol 24: 1594-604 (Added 2011-01-07 10:38:05.458248)
20435010	Kaestner KH From embryonic stem cells to beta-cells: new hope for diabetics? (2010) Gastroenterology 138: 2211-2 (Added 2011-01-07 10:38:05.469426)
20374962	Gu C, Stein GH, Pan N, Goebbels S, Hörnberg H, Nave KA, Herrera P, White P, Kaestner KH, Sussel L, Lee JE Pancreatic beta cells require NeuroD to achieve and maintain functional maturity. (2010) Cell Metab 11: 298-310 (Added 2011-01-07 10:38:05.479429)
20181961	Bhandare R, Schug J, Le Lay J, Fox A, Smirnova O, Liu C, Naji A, Kaestner KH Genome-wide analysis of histone modifications in human pancreatic islets. (2010) Genome Res 20: 428-33 (Added 2011-04-19 12:44:37.68382)
19274050	Hannenhalli S, Kaestner KH null (2009) Nat Rev Genet null: null (Added 2009-03-13 17:37:23)
19208348	Golson ML, Loomes KM, Oakey R, Kaestner KH Ductal malformation and pancreatitis in mice caused by conditional Jag1 deletion. (2009) Gastroenterology 136: 1761-71.e1 (Added 2013-03-01 13:35:19.499227)
19141476	Gao N, LeLay J, Vatamaniuk MZ, Rieck S, Friedman JR, Kaestner KH Dynamic regulation of Pdx1 enhancers by Foxa1 and Foxa2 is essential for pancreas development. (2008) Genes Dev 22: 3435-48 (Added 2011-08-29 09:46:17.412923)
19103808	Hinoi E, Gao N, Jung DY, Yadav V, Yoshizawa T, Myers MG Jr, Chua SC Jr, Kim JK, Kaestner KH, Karsenty G The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity. (2008) J Cell Biol 183: 1235-42 (Added 2009-03-13 17:39:12)
18556755	Tuteja G, Jensen ST, White P, Kaestner KH Cis-regulatory modules in the mammalian liver: composition depends on strength of Foxa2 consensus site. (2008) Nucleic Acids Res 36: 4149-57 (Added 2009-03-13 17:39:20)
18071024	White P, May CL, Lamounier RN, Brestelli JE, Kaestner KH Defining pancreatic endocrine precursors and their descendants. (2008) Diabetes 57: 654-68 (Added 2011-04-19 12:44:37.68382)
17923097	Tuteja G, Kaestner KH Forkhead transcription factors II. (2007) Cell 131: 192 (Added 2009-03-13 17:41:03)
17908556	Gao N, White P, Doliba N, Golson ML, Matschinsky FM, Kaestner KH Foxa2 controls vesicle docking and insulin secretion in mature Beta cells. (2007) Cell Metab 6: 267-79 (Added 2013-03-01 13:35:21.897735)
17889656	Tuteja G, Kaestner KH SnapShot: forkhead transcription factors I. (2007) Cell 130: 1160 (Added 2009-03-13 17:41:17)
17403778	Gupta RK, Gao N, Gorski RK, White P, Hardy OT, Rafiq K, Brestelli JE, Chen G, Stoeckert CJ Jr, Kaestner KH Expansion of adult beta-cell mass in response to increased metabolic demand is dependent on HNF-4{alpha}. (2007) Genes Dev 21: 756-69 (Added 2007-04-14 16:15:48)
17185391	Hardy OT, Hohmeier HE, Becker TC, Manduchi E, Doliba NM, Gupta RK, White P, Stoeckert CJ, Matschinsky FM, Newgard CB, Kaestner KH Functional genomics of the beta-cell: short-chain 3-hydroxyacyl-coenzyme A dehydrogenase regulates insulin secretion independent of K+ currents. (2007) Mol Endocrinol 21: 765-73 (Added 2011-04-19 12:44:37.68382)
17003337	Vatamaniuk MZ, Gupta RK, Lantz KA, Doliba NM, Matschinsky FM, Kaestner KH Foxa1-deficient mice exhibit impaired insulin secretion due to uncoupled oxidative phosphorylation. (2006) Diabetes 55: 2730-6 (Added 2007-04-14 16:16:40)
16725306	Mazzarelli JM, White P, Gorski R, Brestelli J, Pinney DF, Arsenlis A, Katokhin A, Belova O, Bogdanova V, Elisafenko E, Gubina M, Nizolenko L, Perelman P, Puzakov M, Shilov A, Trifonoff V, Vorobjeva N, Kolchanov N, Kaestner KH, Stoeckert CJ Jr Novel genes identified by manual annotation and microarray expression analysis in the pancreas. (2006) Genomics 88: 752-61 (Added 2007-04-14 16:17:04)
16410542	De León DD, Farzad C, Crutchlow MF, Brestelli J, Tobias J, Kaestner KH, Stoffers DA Identification of transcriptional targets during pancreatic growth after partial pancreatectomy and exendin-4 treatment. (2006) Physiol Genomics 24: 133-43 (Added 2011-04-19 12:44:37.68382)
16368785	Hara M, Dizon RF, Glick BS, Lee CS, Kaestner KH, Piston DW, Bindokas VP Imaging pancreatic beta-cells in the intact pancreas. (2006) Am J Physiol Endocrinol Metab 290: E1041-7 (Added 2007-04-14 16:17:58)
16361411	Lee CS, De Leon DD, Kaestner KH, Stoffers DA Regeneration of pancreatic islets after partial pancreatectomy in mice does not involve the reactivation of neurogenin-3. (2006) Diabetes 55: 269-72 (Added 2007-04-14 16:18:17)
15761495	Gupta RK, Vatamaniuk MZ, Lee CS, Flaschen RC, Fulmer JT, Matschinsky FM, Duncan SA, Kaestner KH The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion. (2005) J Clin Invest 115: 1006-15 (Added 2007-04-14 16:18:44)
15680365	Lee CS, Sund NJ, Behr R, Herrera PL, Kaestner KH Foxa2 is required for the differentiation of pancreatic alpha-cells. (2005) Dev Biol 278: 484-95 (Added 2007-04-14 16:19:00)
15631623	Lantz KA, Kaestner KH Winged-helix transcription factors and pancreatic development. (2005) Clin Sci (Lond) 108: 195-204 (Added 2007-04-14 16:19:16)
15519277	Gupta RK, Kaestner KH HNF-4alpha: from MODY to late-onset type 2 diabetes. (2004) Trends Mol Med 10: 521-4 (Added 2007-04-14 16:19:36)
15314688	Lantz KA, Vatamaniuk MZ, Brestelli JE, Friedman JR, Matschinsky FM, Kaestner KH Foxa2 regulates multiple pathways of insulin secretion. (2004) J Clin Invest 114: 512-20 (Added 2011-04-19 12:44:37.68382)
12829622	Kaestner KH, Lee CS, Scearce LM, Brestelli JE, Arsenlis A, Le PP, Lantz KA, Crabtree J, Pizarro A, Mazzarelli J, Pinney D, Fischer S, Manduchi E, Stoeckert CJ, Gradwohl G, Clifton SW, Brown JR, Inoue H, Cras-Méneur C, Permutt MA Transcriptional program of the endocrine pancreas in mice and humans. (2003) Diabetes 52: 1604-10 (Added 2010-08-11 08:33:16.309532)
12209019	Manduchi E, Scearce LM, Brestelli JE, Grant GR, Kaestner KH, Stoeckert CJ Comparison of different labeling methods for two-channel high-density microarray experiments. (2002) Physiol Genomics 10: 169-79 (Added 2010-08-11 08:28:21.405717)
12145169	Lee CS, Sund NJ, Vatamaniuk MZ, Matschinsky FM, Stoffers DA, Kaestner KH Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo. (2002) Diabetes 51: 2546-51 (Added 2005-04-13 12:55:36)
12086925	Scearce LM, Brestelli JE, McWeeney SK, Lee CS, Mazzarelli J, Pinney DF, Pizarro A, Stoeckert CJ Jr, Clifton SW, Permutt MA, Brown J, Melton DA, Kaestner KH Functional genomics of the endocrine pancreas: the pancreas clone set and (2002) Diabetes 51: 1997-2004 (Added 2005-04-13 12:55:30)
12080087	Lee CS, Perreault N, Brestelli JE, Kaestner KH Neurogenin 3 is essential for the proper specification of gastric (2002) Genes Dev 16: 1488-97 (Added 2005-04-13 12:55:28)
12000309	Liu Y, Shen W, Brubaker PL, Kaestner KH, Drucker DJ Foxa3 (HNF-3gamma) binds to and activates the rat proglucagon gene (2002) Biochem J 366: 633-41 (Added 2005-04-13 12:55:38)
11555641	Perreault N, Katz JP, Sackett SD, Kaestner KH Foxl1 controls the Wnt/beta-catenin pathway by modulating the expression (2001) J Biol Chem 276: 43328-33 (Added 2005-04-13 12:50:59)
11546810	Shen W, Scearce LM, Brestelli JE, Sund NJ, Kaestner KH Foxa3 (hepatocyte nuclear factor 3gamma ) is required for the regulation (2001) J Biol Chem 276: 42812-7 (Added 2005-04-13 12:51:01)
11445544	Sund NJ, Vatamaniuk MZ, Casey M, Ang SL, Magnuson MA, Stoffers DA, Matschinsky FM, Kaestner KH Tissue-specific deletion of Foxa2 in pancreatic beta cells results in (2001) Genes Dev 15: 1706-15 (Added 2005-04-13 12:51:04)

Resource ID	Name	Contributed on	Primary Contributor
176	ngn3-EGFP	Mar 7, 2006	Yes
185	Foxa3-Cre	Mar 7, 2006	Yes
1021	Pancreatic developmental time series	Aug 28, 2002	Yes
1022	Beta cell specific ablation of Foxa2 (HNF-3b) in mice	Sep 29, 2003	Yes
1033	GSIS Study of Rat INS1 cell lines	Feb 6, 2004	Yes
1034	Lipotoxicity Study of Rat INS1 cell lines	Feb 18, 2004	Yes
1035	foxA1 and beta cell function	Mar 3, 2004	Yes
1036	HNF4alpha in beta cell function	Mar 5, 2004	Yes
1041	Affymetrix MOE430v2 vs Mouse PancChip 5.0 comparison	Oct 7, 2004	Yes
1053	PANDER Induced Cell-Death Networks in Pancreatic Islets	Feb 6, 2006	Yes
1058	Profile of Neurogenin3 Expression Throughout Embryonic Development of the Endocrine Pancreas in Mice	Dec 10, 2007	Yes
1065	Foxa2 controls vesicle docking and insulin secretion in mature beta-cells	Sep 17, 2007	Yes
1443	Glucocorticoid receptor dependent regulatory networks (Fed and Fasted Mice)	Apr 13, 2009	Yes
1463	Transcriptional Networks in Liver: HNF6 function is largely independent of Foxa2	Apr 13, 2009	Yes
1464	C/EBPbeta Hepatectomy Time Course	Apr 13, 2009	Yes
2903	Transcription profiling of mouse pancreatic islets on day 14.5 of pregnancy	Jan 19, 2010	Yes
4001	Genome-wide Analysis of Histone Modifications in Normal Human Islets	Jul 21, 2010	Yes
4122	FACS of Human Islet Cell Types	Aug 3, 2011
4336	Epigenetics of human pancreatic cells	Apr 24, 2012	Yes
4337	Reprogramming of mouse gall bladder cells into pancreatic beta cells	Apr 24, 2012
4532	Baseline gene expression profile of human extrahepatic biliary cells/biliospheres in vitro	Aug 7, 2012
21 completed resources viewable