J. P. Oettgen, MD

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 667-3390
Fax: (617) 975-5299


joettgen@bidmc.harvard.edu

J. P. Oettgen, MD

Beth Israel Deaconess Medical Center

EDUCATIONAL TITLES

  • Associate Professor, Medicine, Harvard Medical School
  • Director of Prevention, Cardiology, Beth Israel Deaconess Medical Center

Research Abstract

Dr. Peter Oettgen is a member of the Cardiology Division at the Beth Israel Deaconess Medical Center. He is the Director of Preventive Cardiology. His research interests include blood vessel development and angiogenesis. His laboratory is located at the Harvard Institutes of Medicine. His research laboratory is interested in understanding the molecular mechanisms required for the regulation of blood vessel development and vascular inflammation.

One approach used in the laboratory to understanding these biological processes is to identify the transcription factors that act as master switches for these processes. A particular focus has been on the role of one family of transcription factors known as the Ets transcription factor family. Several vascular-specific genes have conserved binding sites for the Ets factors in their genomic regulatory regions. We have identified the specific members of the Ets factor family that regulate the vascular specific tyrosine kinase genes Tie1 and Tie2. These Ets factors are enriched in developing blood vessels during embryogenesis. The identification of the critical transcription factors required for vascular development will promote the development of novel regulators of angiogenesis and endothelial differentiation.

Another area of interest within the laboratory is vascular inflammation. Vascular inflammation is associated with several human diseases. We have identified a transcription factor which is induced very early on in the process of vascular inflammation, and which may help serve as one of the master switches for mediating this process. One of the targets for this factor is an enzyme called nitric oxide synthase, which produces nitric oxide, and important regulator of blood vessel tone and normal function.

Relationship to aging research: Vascular aging has recently been demonstated to be an inflammatory process. Many of the molecular mechanisms identified in regulating vascular inflammation in diseases also apply to the process of vascular aging. It has also been demonstrated that the ability to generate and mobilize endothelial progenitor cells (EPCs) diminishes with aging. A bether understanding of the molecular mechanisms of endothelial differentiation may provide better ways to increase EPCs in the setting of vascular injury or myocardial injury.

Postdoctoral training: Postdoctoral candidates entering the laboratory would be expected to gain basic training in molecular biology, with a particular emphasis on gene transcription. In addition training in stem cell differentiation, and the use of animal models of vascular development and vascular inflammation would be used to study the role of particular transcription factors. Postdoctoral fellows would be expected to attend weekly laboratory meetings, and monthly seminars in vascular biology at Beth Israel Deaconess Medical Center.

Publications

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  • Wang F, Long Q, Gong Y, Hu L, Zhang H, Oettgen P, Peng T. Epithelium-Specific ETS (ESE)-1 upregulated GP73 expression in hepatocellular carcinoma cells. Cell Biosci 2014; 4:76. PubMed
  • Wythe JD, Dang LT, Devine WP, Boudreau E, Artap ST, He D, Schachterle W, Stainier DY, Oettgen P, Black BL, Bruneau BG, Fish JE. ETS factors regulate Vegf-dependent arterial specification. Dev Cell 2013; 26:45-58. PubMed
  • Kato M, Dang V, Wang M, Park JT, Deshpande S, Kadam S, Mardiros A, Zhan Y, Oettgen P, Putta S, Yuan H, Lanting L, Natarajan R. TGF-็กซ induces acetylation of chromatin and of Ets-1 to alleviate repression of miR-192 in diabetic nephropathy. Sci Signal 2013; 6:ra43. PubMed
  • Shirodkar AV, St Bernard R, Gavryushova A, Kop A, Knight BJ, Yan MS, Man HS, Sud M, Hebbel RP, Oettgen P, Aird WC, Marsden PA. A mechanistic role for DNA methylation in endothelial cell (EC)-enriched gene expression: relationship with DNA replication timing. Blood 2013. PubMed
  • Liu J, Yuan L, Molema G, Regan E, Janes L, Beeler D, Spokes KC, Okada Y, Minami T, Oettgen P, Aird WC. Vascular bed-specific regulation of the von Willebrand factor promoter in the heart and skeletal muscle. Blood 2011; 117:342-51. PubMed
  • Zhan Y, Yuan L, Kondo M, Oettgen P. The Counter-Regulatory Effects of ESE-1 During Angiotensin II-Mediated Vascular Inflammation and Remodeling. Am J Hypertens 2010; 23:1312-7. PubMed
  • Harris TA, Yamakuchi M, Kondo M, Oettgen P, Lowenstein CJ. Ets-1 and Ets-2 regulate the expression of microRNA-126 in endothelial cells. Arterioscler Thromb Vasc Biol 2010; 30:1990-7. PubMed
  • Le Bras A, Vijayaraj P, Oettgen P. Molecular mechanisms of endothelial differentiation. Vasc Med 2010; 15:321-31. PubMed
  • Bhasin M, Yuan L, Keskin DB, Otu HH, Libermann TA, Oettgen P. Bioinformatic identification and characterization of human endothelial cell-restricted genes. BMC Genomics 2010; 11:342. PubMed
  • Oettgen P. The role of ets factors in tumor angiogenesis. J Oncol 2010; 2010:767384. PubMed
  • Jin E, Liu J, Suehiro J, Yuan L, Okada Y, Nikolova-Krstevski V, Yano K, Janes L, Beeler D, Spokes KC, Li D, Regan E, Shih SC, Oettgen P, Minami T, Aird WC. Differential roles for ETS, CREB, and EGR binding sites in mediating VEGF receptor 1 expression in vivo. Blood 2009; 114:5557-66. PubMed
  • Song H, Suehiro J, Kanki Y, Kawai Y, Inoue K, Daida H, Yano K, Ohhashi T, Oettgen P, Aird WC, Kodama T, Minami T. Critical role for GATA3 in mediating Tie2 expression and function in large vessel endothelial cells. J Biol Chem 2009; 284:29109-24. PubMed
  • Oettgen P. Functional redundancy of Ets1 and Ets2. Blood 2009; 114:934-5. PubMed
  • Nikolova-Krstevski V, Yuan L, Le Bras A, Vijayaraj P, Kondo M, Gebauer I, Bhasin M, Carman CV, Oettgen P. ERG is required for the differentiation of embryonic stem cells along the endothelial lineage. BMC Dev Biol 2010; 9:72. PubMed
  • Melero-Martin JM,De Obaldia ME,Kang SY,Khan ZA,Yuan L,Oettgen P,Bischoff J. Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ Res 2008; 103:194-202. PubMed
  • Nikolova-Krstevski V, Bhasin M, Otu HH, Libermann T, Oettgen P. Gene expression analysis of embryonic stem cells expressing VE-cadherin (CD144) during endothelial differentiation. BMC Genomics 2008; 9:240. PubMed
  • Ni W, Zhan Y, He H, Maynard E, Balschi JA, Oettgen P. Ets-1 is a critical transcriptional regulator of reactive oxygen species and p47(phox) gene expression in response to angiotensin II. Circ Res 2007; 101:985-94. PubMed
  • Okada Y, Yano K, Jin E, Funahashi N, Kitayama M, Doi T, Spokes K, Beeler DL, Shih SC, Okada H, Danilov TA, Maynard E, Minami T, Oettgen P, Aird WC. A three-kilobase fragment of the human Robo4 promoter directs cell type-specific expression in endothelium. Circ Res 2007; 100:1712-22. PubMed
  • Oettgen P. Regulation of vascular inflammation and remodeling by ETS factors. Circ Res 2006; 99:1159-66. PubMed
  • Oettgen P, Boyle AJ, Schulman SP, Hare JM. Cardiac Stem Cell Therapy. Need for Optimization of Efficacy and Safety Monitoring. Circulation 2006; 114:353-8. PubMed
  • Min JY, Huang X, Xiang M, Meissner A, Chen Y, Ke Q, Kaplan E, Rana JS, Oettgen P, Morgan JP. Homing of intravenously infused embryonic stem cell-derived cells to injured hearts after myocardial infarction. J Thorac Cardiovasc Surg 2006; 131:889-97. PubMed
  • Brown C, Gaspar J, Pettit A, Lee R, Gu X, Wang H, Manning C, Voland C, Goldring SR, Goldring MB, Libermann TA, Gravalllese EM, Oettgen P. ESE-1 is a novel transcriptional mediator of angiopoietin-1 expression in the setting of inflammation. J Biol Chem 2004; 279:12794-803. PubMed
  • Bates RC, Goldsmith JD, Bachelder RE, Brown C, Shibuya M, Oettgen P, Mercurio AM. Flt-1-dependent survival characterizes the epithelial-mesenchymal transition of colonic organoids. Curr Biol 2003; 13:1721-7. PubMed
  • Gaspar J, Thai S, Voland C, Dube A, Libermann TA, Iruela-Arispe ML, Oettgen P. Opposing functions of the Ets factors NERF and ELF-1 during chicken blood vessel development. Arterioscler Thromb Vasc Biol 2002; 22:1106-12. PubMed
  • Christensen RA, Fujikawa K, Madore R, Oettgen P, Varticovski L. NERF2, a member of the Ets family of transcription factors, is increased in response to hypoxia and angiopoietin-1: a potential mechanism for Tie2 regulation during hypoxia. J Cell Biochem 2002; 85:505-15. PubMed
  • Oettgen P. Transcriptional regulation of vascular development. Circ Res 2001; 89:380-8. PubMed
  • Gu X, Shin BH, Akbarali Y, Weiss A, Boltax J, Oettgen P, Libermann TA. Tel-2 is a novel transcriptional repressor related to the Ets factor Tel/ETV-6. J Biol Chem 2000; 276:9421-36. PubMed
  • Rudders S, Gaspar J, Madore R, Voland C, Grall F, Patel A, Pellacani A, Perrella MA, Libermann TA, Oettgen P. ESE-1 is a novel transcriptional mediator of inflammation that interacts with NF-kappa B to regulate the inducible nitric-oxide synthase gene. J Biol Chem 2000; 276:3302-9. PubMed
  • Dube A, Thai S, Gaspar J, Rudders S, Libermann TA, Iruela-Arispe L, Oettgen P. Elf-1 is a transcriptional regulator of the Tie2 gene during vascular development. Circ Res 2001; 88:237-44. PubMed
  • Kas K, Finger E, Grall F, Gu X, Akbarali Y, Boltax J, Weiss A, Oettgen P, Kapeller R, Libermann TA. ESE-3, a novel member of an epithelium-specific ets transcription factor subfamily, demonstrates different target gene specificity from ESE-1. J Biol Chem 2000; 275:2986-98. PubMed
  • Oettgen P, Finger E, Sun Z, Akbarali Y, Thamrongsak U, Boltax J, Grall F, Dube A, Weiss A, Brown L, Quinn G, Kas K, Endress G, Kunsch C, Libermann TA. PDEF, a novel prostate epithelium-specific ets transcription factor, interacts with the androgen receptor and activates prostate-specific antigen gene expression. J Biol Chem 2000; 275:1216-25. PubMed
  • Oettgen P, Kas K, Dube A, Gu X, Grall F, Thamrongsak U, Akbarali Y, Finger E, Boltax J, Endress G, Munger K, Kunsch C, Libermann TA. Characterization of ESE-2, a novel ESE-1-related Ets transcription factor that is restricted to glandular epithelium and differentiated keratinocytes. J Biol Chem 1999; 274:29439-52. PubMed
  • Dube A, Akbarali Y, Sato TN, Libermann TA, Oettgen P. Role of the Ets transcription factors in the regulation of the vascular-specific Tie2 gene. Circ Res 1999; 84:1177-85. PubMed
  • Oettgen P, Barcinski M, Boltax J, Stolt P, Akbarali Y, Libermann TA. Genomic organization of the human ELF3 (ESE-1/ESX) gene, a member of the Ets transcription factor family, and identification of a functional promoter. Genomics 1999; 55:358-62. PubMed
  • Iljin K, Dube A, Kontusaari S, Korhonen J, Lahtinen I, Oettgen P, Alitalo K. Role of ets factors in the activity and endothelial cell specificity of the mouse Tie gene promoter. FASEB J 1999; 13:377-86. PubMed
  • Sata M, Perlman H, Muruve DA, Silver M, Ikebe M, Libermann TA, Oettgen P, Walsh K. Fas ligand gene transfer to the vessel wall inhibits neointima formation and overrides the adenovirus-mediated T cell response. Proc Natl Acad Sci U S A 1998; 95:1213-7. PubMed
  • Oettgen P, Carter KC, Augustus M, Barcinski M, Boltax J, Kunsch C, Libermann TA. The novel epithelial-specific Ets transcription factor gene ESX maps to human chromosome 1q32.1. Genomics 1998; 45:456-7. PubMed
  • Oettgen P, Alani RM, Barcinski MA, Brown L, Akbarali Y, Boltax J, Kunsch C, Munger K, Libermann TA. Isolation and characterization of a novel epithelium-specific transcription factor, ESE-1, a member of the ets family. Mol Cell Biol 1997; 17:4419-33. PubMed
  • Akbarali Y, Oettgen P, Boltax J, Libermann TA. ELF-1 interacts with and transactivates the IgH enhancer pi site. J Biol Chem 1996; 271:26007-12. PubMed
  • Oettgen P, Akbarali Y, Boltax J, Best J, Kunsch C, Libermann TA. Characterization of NERF, a novel transcription factor related to the Ets factor ELF-1. Mol Cell Biol 1996; 16:5091-106. PubMed
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