John P. O'Rourke Jr., PhD
Research Assistant Professor
Molecular Genetics and Microbiology
MSC08 4660
University of New Mexico HSC
915 Camino de Salud NE
Albuquerque, NM 87131-0001
 
Office: CRF 119
Tel: (505) 272-3463
Fax: (505) 272-3464
E-mail: JORourkeJr@salud.unm.edu

Keywords: Alternative splicing; Hematopoiesis, Leukemogenesis; mammary gland biology; viral vectors

Research Interests

Up to 74% of all human genes undergo alternative splicing.  However, the role that alternative splicing plays in normal cell biology or tumorigenesis is poorly understood.   My research focuses on global changes in alternative splicing during hematopoiesis and leukemogenesis and in particular, changes in the splicing repertoire of the proto-oncogene c-myb.  By using viral vectors and exon specific gene arrays during in vitro differentiation of primary hematopoietic cells, we are discovering novel biological functions of the various alternatively spliced c-Myb isoforms.  Another emphasis of research is investigating the Myb family members in the control of mammary gland cell growth and apoptosis.  Using viral vector based RNAi and expression contructs in novel 3-D mammary culture systems we are attempting to probe signaling pathways regulated by different Myb family members.

Recent publications:

O’Rourke JP and Ness SA. Lineage Specific Alternate Splicing Produces Multiple Forms of c-Myb with Unique Transcriptional Activities.  Manuscript in preparation.    

Liu F, Lei W, O’Rourke JP, Ness SA.  Oncogenic Mutations Cause Dramatic, Qualitative Changes in the Transcriptional Activity of c-Myb. Oncogene. 2006 Feb 2;25(5):795-805.

O’Rourke JP, Olsen JC, Bunnell BA.  Optimization of Equine Infectious Anemia Derived Vectors for Hematopoietic Cell Lineage Gene Transfer. Gene Ther  2005 Jan;12(1):22-29.

O’Rourke JP, Hiraragi H, Urban K, Patel M, Olsen JC, Bunnell BA.  Analysis of gene transfer and expression in skeletal muscle using enhanced EIAV lentivirus vectors. Mol Ther. 2003 May;7(5):632-9.

O’Rourke JP, Newbound GC, Kohn DB, Olsen JC, Bunnell, BA. Comparison of Gene Transfer Efficiency and Gene Expression with EIAV and HIV-1 Derived Lentivirus Vectors. J. Virology.  2002 Feb;76(3): 1510-1515.

O'Rourke JP, Tarantal AF, Case SS, Newbound GC, Li J, Lee CI, Baskin CR, Kohn DB, Bunnell BA.  Rhesus monkey model for fetal gene transfer: studies with retroviral- based vector systems. Mol Ther  2001 Feb;3(2):128-38.

Newbound GC, Cooper JR, O'Rourke JP, Baskin CR, Bunnell BA.  Analysis of gene transfer efficiency of retrovirus producer cell transplantation for in situ gene transfer to hematopoietic cells.  Exp Hematol  2001 Feb;29(2):163-73.

Newbound GC, O'Rourke JP, Collins ND, Andrews JM, DeWille J, Lairmore MD. Repression of tax-mediated human t-lymphotropic virus type 1 transcription by inducible cAMP early repressor (ICER) protein in peripheral blood mononuclear cells.  J Med Virol  2000 Oct;62(2):286-92.

Hutt JA, O'Rourke JP, DeWille J. Signal transducer and activator of transcription 3 activates CCAAT enhancer-binding protein delta gene transcription in G0 growth-arrested mouse mammary epithelial cells and in involuting mouse mammary gland.  J Biol Chem  2000 Sep 15;275(37):29123-31.

O'Rourke JP, Hutt JA, DeWille J. Transcriptional regulation of C/EBP delta in G₀ growth-arrested mouse mammary epithelial cells.  Biochem Biophys Res Commun  1999 Sep 7;262(3):696-701.

O'Rourke JP, Newbound GC, Hutt JA, DeWille J. CCAAT/enhancer-binding protein delta regulates mammary epithelial cell G0 growth arrest and apoptosis. J Biol Chem  1999 Jun 4;274(23):16582-9.

Newbound GC, O'Rourke JP, Collins ND, DeWille J, Lairmore MD.  Comparison of HTLV-I basal transcription and expression of CREB/ATF-1/CREM family members in peripheral blood mononuclear cells and Jurkat T cells. J Acquir Immune Defic Syndr Hum Retrovirol  1999 Jan 1;20(1):1-10

Werkmeister JR, Blomme EA, Weckmann MT, Grone A, McCauley LK, Wade AB, O'Rourke JP, Capen CC, Rosol TJ. Effect of transforming growth factor-beta1 on parathyroid hormone-related protein secretion and mRNA expression by normal human keratinocytes in vitro.  Endocrine 1998 Jun;8(3):291-9.

O'Rourke JP, Yuan R, DeWille J.  CCAAT/enhancer-binding protein-delta (C/EBP-delta) is induced in growth-arrested mouse mammary epithelial cells. J Biol Chem  1997 Mar 7;272(10):6291-6.

Newbound GC, Andrews JM, O'Rourke JP, Brady JN, Lairmore MD.  Human T-cell lymphotropic virus type 1 Tax mediates enhanced transcription in CD4+ T lymphocytes. J Virol  1996 Apr;70(4):2101-6.