Robin C. Muise-Helmericks, Ph.D.
Room 654, Basic Science Building
Office: (843) 792-4760
AA Zoology Palm Beach Junior College 1981
BS Microbiology Florida Atlantic University 1984
PhD University of Florida 1991
The overall objective of my laboratory is to understand the molecular and cellular mechanisms involved in (1) vasculo/angiogenesis and (2) lymphoid development, specifically focusing on the Ets family of transcription factors. Vasculogenesis and angiogenesis are crucial events in embryonic development, wound healing and in the pathology of solid tumors. Ets1, the founding member of the Ets family, plays an essential role in this process; inhibition of Ets1 expression blocks tube formation. We have taken a number of approaches to determine the role of Ets1 and functionally redundant family members in angiogenesis. The first uses an in vitro primary culture system to dissect upstream signaling pathways responsible for the control of Ets1 expression and activity and to determine the specific downstream target genes. The second approach uses two in vivo systems to confirm the function of Ets1 and its upstream signaling components. One involves a Drosophila-based system and the other is an inducible mammalian transgenic system.
In addition to its proposed role in angiogenesis Ets1 expression has been shown to affect normal hematopoiesis. Knockout animals have clear lymphoid defects. We are using an in vitro system to determine the regulation of Ets1 expression and/or activity by IL-2 in NK cells. We are also using transgenic animals to determine the role of the two different Ets1 isoforms, p51 and a splice variant, p42, in lymphoid development.
Understanding the mechanisms of these two important developmental processes has become a major goal, both in research institutes and pharmaceutical industries, in combating diseases such as birth defects, cardiovascular abnormalities, immunodeficiency's and cancers. Our hopes are that this research will lead to greater understanding of these processes and identify suitable targets for gene- and/or chemo-therapies.
- Beeson CC, Beeson GC, Buff H, Eldridge J, Zhang A, Seth A, Demcheva M, Vournakis JN, Muise-Helmericks RC. Integrin-dependent Akt1 activation regulates PGC-1 expression and fatty acid oxidation. J Vasc Res. 2012;49(2):89-100. doi: 10.1159/000332326. Epub 2012 Jan 13.
- Muise-Helmericks RC, Demcheva M, Vournakis JN, Seth A. Poly-N-acetyl glucosamine fibers activate bone regeneration in a rabbit femur injury model. J Trauma. 2011 Aug;71(2 Suppl 1):S194-6.
- Lindner HB, Zhang A, Eldridge J, Demcheva M, Tsichlis P, Seth A, Vournakis J, Muise-Helmericks RCAnti-bacterial effects of poly-N-acetyl-glucosamine nanofibers in cutaneous wound healing: requirement for Akt1. PLoS One. 2011 Apr 29;6(4):e18996. Erratum in: PLoS One. 2011;6(7). doi: 10.1371/annotation/3966fcd7-6127-45e0-80e6-55063875e826. Tsichilis, Philip [corrected to Tsichlis, Philip].
- Liby TA, Spyropoulos P, Buff Lindner H, Eldridge J, Beeson C, Hsu T, Muise-Helmericks RC. Akt3 controls vascular endothelial growth factor secretion and angiogenesis in ovarian cancer cells. Int J Cancer. 2012 Feb 1;130(3):532-43. doi: 10.1002/ijc.26010. Epub 2011 Apr 20.
- Scherer SS, Pietramaggiori G, Matthews J, Perry S, Assmann A, Carothers A, Demcheva M, Muise-Helmericks RC, Seth A, Vournakis JN, Valeri RC, Fischer TH, Hechtman HB, Orgill DP. Poly-N-acetyl glucosamine nanofibers: a new bioactive material to enhance diabetic wound healing by cell migration and angiogenesis. Ann Surg. 2009 Aug;250(2):322-30. Erratum in: Ann Surg.2009 Oct;250(4):661.
- Wright GL, Maroulakou IG, Eldridge J, Liby TL, Sridharan V, Tsichlis PN, Muise-Helmericks RC. VEGF stimulation of mitochondrial biogenesis: requirement of AKT3 kinase. FASEB J. 2008 Sep;22(9):3264-75. Epub 2008 Jun 4.
- Sridharan V, Guichard J, Li CY, Muise-Helmericks R, Beeson CC, Wright GL. Am O(2)-sensing signal cascade: clamping of O(2) respiration, reduced ATP utilization, and inducible fumarate respiration. J Physiol Cell Physiol. 2008 Jul;295(1):C29-37. Epub 2008 May 7.
- Bujor AM, Pannu J, Bu S, Smith EA, Muise-Helmericks RC, Trojanowska M. Akt blockade downregulates collagen and upregulates MMP1 in human dermal fibroblasts. J Invest Dermatol. 2008 Aug;128(8):1906-14. Epub 2008 Mar 6.
- Vournakis JN, Eldridge J, Demcheva M, Muise-Helmericks RC. Poly-N-acetyl glucosamine nanofibers regulate endothelial cell movement and angiogenesis: dependency on integrin activation of Ets1. J Vasc Res. 2008;45(3):222-32. Epub 2007 Dec 19.
- Higuchi T, Bartel FO, Masuya M, Deguchi T, Henderson KW, Li R, Muise-Helmericks RC, Kern MJ, Watson DK, Spyropoulos DD. Thymomegaly, microsplenia, and defective homeostatic proliferation of peripheral lymphocytes in p51-Ets1 isoform-specific null mice. Mol Cell Biol. 2007 May;27(9):3353-66. Epub 2007 Mar 5.
- Fieber CB, Eldridge J, Taha TA, Obeid LM, Muise-Helmericks RC. Modulation of total Akt kinase by increased expression of a single isoform: requirement of the sphingosine-1-phosphate receptor, Edg3/S1P3, for the VEGF-dependent expression of Akt3 in primary endothelial cells. Exp Cell Res. 2006 Apr 15;312(7):1164-73. Epub 2006 Mar 9.
- Grund EM, Muise-Helmericks RC. Cost efficient and effective gene transfer into the human natural killer cell line, NK92. J Immunol Methods. 2005 Jan;296(1-2):31-6. Epub 2004 Nov 24.
- Grund EM, Spyropoulos DD, Watson DK, Muise-Helmericks RC. Interleukins 2 and 15 regulate Ets1 expression via ERK1/2 and MNK1 in human natural killer cells. J Biol Chem. 2005 Feb 11;280(6):4772-8. Epub 2004 Nov 23.
- Yordy JS, Li R, Sementchenko VI, Pei H, Muise-Helmericks RC, Watson DK. SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion. Oncogene. 2004 Aug 26;23(39):6654-65.
- Lavenburg KR, Ivey J, Hsu T, Muise-Helmericks RC. Coordinated functions of Akt/PKB and ETS1 in tubule formation. FASEB J. 2003 Dec;17(15):2278-80. Epub 2003 Oct 2.
- Maroulakou IG, Muise-Helmericks RC. Guide to techniques in creating transgenic mouse models using SV40 T antigen. Methods Mol Biol. 2001;165:269-86.
- Yordy JS, Muise-Helmericks RC. Signal transduction and the Ets family of transcription factors. Oncogene. 2000 Dec 18;19(55):6503-13.
- Muise-Helmericks RC, Grimes HL, Bellacosa A, Malstrom SE, Tsichlis PN, Rosen N. Cyclin D expression is controlled post-transcriptionally via a phosphatidylinositol 3-kinase/Akt-dependent pathway. J Biol Chem. 1998 Nov 6;273(45):29864-72.
- Muise-Helmericks RC, Rosen N. Identification of a novel repressive element in the proximal lck promoter. J Biol Chem. 1995 Nov 17;270(46):27538-43.
- Muise RC, Hauswirth WW. Selective DNA amplification regulates transcript levels in plant mitochondria. Curr Genet. 1995 Jul;28(2):113-21.