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
  • Mass. Chemical and biomechanical characterization of hyperhomocysteinemic bone disease in an animal model. BMC Musculoskelet Disord 2003; 4:2. PubMed
  • Danciu TE, Adam RM, Naruse K, Freeman MR, Hauschka PV. Calcium regulates the PI3K-Akt pathway in stretched osteoblasts. FEBS Lett 2003; 536:193-7. PubMed
  • Wang ML, Hauschka PV, Tuan RS, Steinbeck MJ. Exposure to particles stimulates superoxide production by human THP-1 macrophages and avian HD-11EM osteoclasts activated by tumor necrosis factor-alpha and PMA. J Arthroplasty 2002; 17:335-46. PubMed
  • Solomon KR, Adolphson LD, Wank DA, McHugh KP, Hauschka PV. Caveolae in human and murine osteoblasts. J Bone Miner Res 2000; 15:2391-401. PubMed
  • Chen L, Adar R, Yang X, Monsonego EO, Li C, Hauschka PV, Yayon A, Deng CX. Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis. J Clin Invest 1999; 104:1517-25. PubMed
  • Steinbeck MJ, Kim JK, Trudeau MJ, Hauschka PV, Karnovsky MJ. Involvement of hydrogen peroxide in the differentiation of clonal HD-11EM cells into osteoclast-like cells. J Cell Physiol 1998; 176:574-87. PubMed
  • Hauschka PV, Damoulis PD. Functions of nitric oxide in bone. Biochem Soc Trans 2000; 26:39-44. PubMed
  • Damoulis PD, Hauschka PV. Nitric oxide acts in conjunction with proinflammatory cytokines to promote cell death in osteoblasts. J Bone Miner Res 1997; 12:412-22. PubMed
  • Nagy L, Kusstatscher S, Hauschka PV, Szabo S. Role of cysteine proteases and protease inhibitors in gastric mucosal damage induced by ethanol or ammonia in the rat. J Clin Invest 1996; 98:1047-54. PubMed
  • Hunter GK, Hauschka PV, Poole AR, Rosenberg LC, Goldberg HA. Nucleation and inhibition of hydroxyapatite formation by mineralized tissue proteins. Biochem J 1996; 317 ( Pt 1):59-64. PubMed
  • Asahina I, Sampath TK, Hauschka PV. Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells. Exp Cell Res 1996; 222:38-47. PubMed
  • Atkinson RA, Evans JS, Hauschka PV, Levine BA, Meats R, Triffitt JT, Virdi AS, Williams RJ. Conformational studies of osteocalcin in solution. Eur J Biochem 1995; 232:515-21. PubMed
  • Neugebauer BM, Moore MA, Broess M, Gerstenfeld LC, Hauschka PV. Characterization of structural sequences in the chicken osteocalcin gene: expression of osteocalcin by maturing osteoblasts and by hypertrophic chondrocytes in vitro. J Bone Miner Res 1995; 10:157-63. PubMed
  • Damoulis PD, Hauschka PV. Cytokines induce nitric oxide production in mouse osteoblasts. Biochem Biophys Res Commun 1994; 201:924-31. PubMed
  • Maliakal JC, Asahina I, Hauschka PV, Sampath TK. Osteogenic protein-1 (BMP-7) inhibits cell proliferation and stimulates the expression of markers characteristic of osteoblast phenotype in rat osteosarcoma (17/2.8) cells. Growth Factors 1994; 11:227-34. PubMed
  • Asahina I, Sampath TK, Nishimura I, Hauschka PV. Human osteogenic protein-1 induces both chondroblastic and osteoblastic differentiation of osteoprogenitor cells derived from newborn rat calvaria. J Cell Biol 1993; 123:921-33. PubMed
  • McKee MD, Farach-Carson MC, Butler WT, Hauschka PV, Nanci A. Ultrastructural immunolocalization of noncollagenous (osteopontin and osteocalcin) and plasma (albumin and alpha 2HS-glycoprotein) proteins in rat bone. J Bone Miner Res 1993; 8:485-96. PubMed
  • Taichman RS, Hauschka PV. Effects of interleukin-1 beta and tumor necrosis factor-alpha on osteoblastic expression of osteocalcin and mineralized extracellular matrix in vitro. Inflammation 1992; 16:587-601. PubMed
  • Spampata R, Werther JR, Hauschka PV. Accelerated endochondral osteoinduction in the absence of bone matrix particles in a rat model system. J Oral Maxillofac Surg 1992; 50:140-51; discussion 151-2. PubMed
  • Nguyen L, Dewhirst FE, Hauschka PV, Stashenko P. Interleukin-1 beta stimulates bone resorption and inhibits bone formation in vivo. Lymphokine Cytokine Res 1991; 10:15-21. PubMed
  • Vernillo AT, Rifkin BR, Hauschka PV. Phenytoin affects osteocalcin secretion from osteoblastic rat osteosarcoma 17/2.8 cells in culture. Bone 1990; 11:309-12. PubMed
  • Hauschka PV, Lian JB, Cole DE, Gundberg CM. Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 1989; 69:990-1047. PubMed
  • Auf'mkolk B, Hauschka PV, Schwartz ER. Characterization of human bone cells in culture. Calcif Tissue Int 1985; 37:228-35. PubMed
  • Boskey AL, Wians FH, Hauschka PV. The effect of osteocalcin on in vitro lipid-induced hydroxyapatite formation and seeded hydroxyapatite growth. Calcif Tissue Int 1984; 37:57-62. PubMed
  • Hauschka PV, Frenkel J, DeMuth R, Gundberg CM. Presence of osteocalcin and related higher molecular weight 4-carboxyglutamic acid-containing proteins in developing bone. J Biol Chem 1983; 258:176-82. PubMed
  • Hauschka PV, Carr SA. Calcium-dependent alpha-helical structure in osteocalcin. Biochemistry 1982; 21:2538-47. PubMed
  • Lian JB, Glimcher MJ, Roufosse AH, Hauschka PV, Gallop PM, Cohen-Solal L, Reit B. Alterations of the gamma-carboxyglutamic acid and osteocalcin concentrations in vitamin D-deficient chick bone. J Biol Chem 1982; 257:4999-5003. PubMed
  • Hauschka PV, Carr SA, Biemann K. Primary structure of monkey osteocalcin. Biochemistry 1982; 21:638-42. PubMed
  • Carr SA, Hauschka PV, Biemann K. Gas chromatographic mass spectrometric sequence determination of osteocalcin, a gamma-carboxyglutamic acid-containing protein from chicken bone. J Biol Chem 1981; 256:9944-50. PubMed
  • Gallop PM, Lian JB, Hauschka PV. Carboxylated calcium-binding proteins and vitamin K. N Engl J Med 1980; 302:1460-6. PubMed
  • Hauschka PV. Quantitative determination of gamma-carboxyglutamic acid in proteins. Anal Biochem 1977; 80:212-23. PubMed
  • Hauschka PV, Lian JB, Gallop PM. Direct identification of the calcium-binding amino acid, gamma-carboxyglutamate, in mineralized tissue. Proc Natl Acad Sci U S A 1975; 72:3925-9. PubMed
  • Hauschka PV. Analysis of nucleotide pools in animal cells. Methods Cell Biol 1972; 7:361-462. PubMed
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