Peter V. Hauschka, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2950
Fax: (617) 919-2952


peter.hauschka@childrens.harvard.edu

Peter V. Hauschka, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Associate Professor, Orthopaedic Surgery, Harvard Medical School
  • Senior Research Associate, Orthopaedic Surgery, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Osteolytic Tumors in Bone: Metastatic breast adenocarcinoma and multiple myeloma cause morbidity and death because of tumor cell interference and "takeover" of the normal regulatory pathways involving bone marrow stromal cells, osteoblasts, and resorptive osteoclasts. We are investigating human breast cancer cells, testing the hypothesis that mimicry of the osteoblast phoneotype provides survival advantages in skeletal metastatic sites. Interaction of breast adnocarcinoma cells with normal bone marrow stromal cells in the metatstatic site stimulates osteoclast dvelopment and bone destruction. We are testing whether the osteolytic reaction to breast adenocarcinoma cells is achieved by upregulation of the osteoclast differentiation receptor, RANK, or its ligand (RANKL), or downregulation of the protective decoy receptor osteoprotegerin (OPG). The identical receptor (RANK) and ligand (RANKL) determine the survival of dendritic cells (antigen-presenting cells) for the continued instruction of T-cells.

Osteolytic Tumors in Bone: Metastatic breast adenocarcinoma and multiple myeloma cause morbidity and death because of tumor cell interference and "takeover" of the normal regulatory pathways involving bone marrow stromal cells, osteoblasts, and resorptive osteoclasts. Interaction of breast adenocarcinoma cells with normal bone marrow stromal cells in the metastatic site stimulates osteoclast development and bone destruction. We are investigating human breast cancer cells, testing two hypotheses: 1) does breast cancer mimicry of the osteoblast phenotype provide survival advantages in skeletal metastatic sites? and 2) is the osteolytic reaction to breast adenocarcinoma cells is achieved by upregulation of the osteoclast differentiation receptor, RANK, or its ligand RANKL, or downregulation of the protective decoy receptor osteoprotegerin OPG? The identical RANK-RANKL receptor-ligand pair determine the survival of dendritic cells (antigen-presenting cells) for the continued instruction of T-cells.

Publications

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  • Phillips JA, Mortensen LJ, Ruiz JP, Sridharan R, Kumar S, Torres M, Sharma P, Lin CP, Karp JM, Hauschka PV. Advances in Single-cell Tracking of Mesenchymal Stem Cells (MSCs) During Musculoskeletal Regeneration. Orthop J Harv Med Sch 2013; 14:22-28. PubMed
  • Zhang Z, Wang H, Ikeda S, Fahey F, Bielenberg D, Smits P, Hauschka PV. Notch3 in human breast cancer cell lines regulates osteoblast-cancer cell interactions and osteolytic bone metastasis. Am J Pathol 2010; 177:1459-69. PubMed
  • Sharma P, Patntirapong S, Hann S, Hauschka PV. RANKL-RANK signaling regulates expression of xenotropic and polytropic virus receptor (XPR1) in osteoclasts. Biochem Biophys Res Commun 2010; 399:129-32. PubMed
  • Cai X, Lin Y, Friedrich CC, Neville C, Pomerantseva I, Sundback CA, Sharma P, Zhang Z, Vacanti JP, Hauschka PV, Grottkau BE. Bone marrow derived pluripotent cells are pericytes which contribute to vascularization. Stem Cell Rev 2010; 5:437-45. PubMed
  • Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature 2009; 460:259-63. PubMed
  • Kozloff KM,Quinti L,Patntirapong S,Hauschka PV,Tung CH,Weissleder R,Mahmood U. Non-invasive optical detection of cathepsin K-mediated fluorescence reveals osteoclast activity in vitro and in vivo. Bone 2008; 44:190-8. PubMed
  • Yang Q,McHugh KP,Patntirapong S,Gu X,Wunderlich L,Hauschka PV. VEGF enhancement of osteoclast survival and bone resorption involves VEGF receptor-2 signaling and beta3-integrin. Matrix Biol 2008; 27:589-99. PubMed
  • Krum SA, Miranda-Carboni GA, Hauschka PV, Carroll JS, Lane TF, Freedman LP, Brown M. Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival. EMBO J 2008; 27:535-45. PubMed
  • MacDonald BT, Joiner DM, Oyserman SM, Sharma P, Goldstein SA, He X, Hauschka PV. Bone mass is inversely proportional to Dkk1 levels in mice. Bone 2007; 41:331-9. PubMed
  • Sharma P, Solomon KR, Hauschka PV. High-throughput tool for discovery of bone regulating factors. Biotechniques 2006; 41:539-40, 542. PubMed
  • Gagari E, Rand MK, Tayari L, Vastardis H, Sharma P, Hauschka PV, Damoulis PD. Expression of stem cell factor and its receptor, c-kit, in human oral mesenchymal cells. Eur J Oral Sci 2006; 114:409-15. PubMed
  • Boucher K, Siegel CS, Sharma P, Hauschka PV, Solomon KR. HMG-CoA reductase inhibitors induce apoptosis in pericytes. Microvasc Res 2006; 71:91-102. PubMed
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