UPMC Hillman Cancer Center

Deborah L. Galson, PhD

Deborah Galson
Associate Professor of Medicine, Division of Hematology/Oncology
Associate Professor of Microbiology & Molecular Genetics
Director, Pittsburgh Center for Bone & Mineral Research

Contact Information

Contact Information

Hillman Cancer Center Suite 1.19b
5117 Centre Avenue
Pittsburgh, PA 15213

Phone: 412-623-7735
Email: galson@pitt.edu
Fax: 412-623-1415

Administrative Assistant
Name: Dianna Fennell
Phone: 412-623-1114
Email: pappertfenneld@upmc.edu
Fax: 412-623-1415

Research Keywords

Research Keywords

Multiple myeloma; breast cancer; cancer-induced bone disease; signal transduction; epigenetic regulation; transcription factors; bone biology; Paget's disease

Research Summary

Research Summary

Dr. Deborah Galson’s laboratory is focused on two main areas:

(1) Determining the mechanism by which multiple myeloma (MM) cells reduce bone formation via suppression of the differentiation capacity of osteoblast progenitor cells in a manner that persists even after removal of the myeloma cells. These MM-altered bone marrow stromal cells also enhance osteoclastogenesis and microenvironmental support of myeloma growth. We have shown that myeloma cells induce the upregulation of expression of the transcriptional repressor Gfi1 in osteoblast precursor cells and that Gfi1 has a role in repressing Runx2, the key osteoblast transcription factor. We are currently investigating the mechanisms by which Gfi1 represses Runx2; MM cells and TNF-alpha/IL-7 regulate Gfi1 expression and activity; and roles for Gfi1 in MM cells and osteoclasts. Our preliminary data suggests that Gfi1 may prove to be a useful 3-way therapeutic target in MM bone disease. We are also expanding these studies into other cancer-induced bone disease models and into inflammatory diseases that cause bone formation suppression.

(2) Determining the mechanism by which measles virus nucleocapsid protein (MVNP) activates cellular genes and alters osteoclast differentiation. MVNP has been shown to be able to induce a Pagetic phenotype when transduced into osteoclast precursors and there is increasing evidence that it can play a role in the development of Paget’s disease. Understanding the mechanisms involved may aid in developing additional treatments for Paget’s disease as well as increase our understanding of how viral proteins alter cells. We have made the important discovery that MVNP signals through the IKK family members TBK1 and IKKepsilon to increase IL-6, a key player in creating the pagetic microenvironment. We are also studying MVNP regulation of C/EBPbeta and FoxO proteins, as well as autophagy, in generating aberrant osteoclasts. We have found that MVNP alters both the level of C/EBPbeta expression as well as the translation regulation of the C/EBPbeta LAP/LIP isoforms ratio. MVNP also alters the regulation of FoxO1 cellular localization, preventing nuclear localization, which increases autophagy, Further, MVNP alters the stability of FoxO3a, leading to rapid degradation and loss of SIRT1 expression, which thereby increases NF-kappaB activity. We are expanding the investigation of TBK1 and IKKepsilon signal transduction into other disease models that elevate osteoclasts including cancer-induced bone disease and arthritis.

Selected Publications

Selected Publications

  • Sun Q, Sammut B, Wang FM, Kurihara N, Windle JJ, Roodman GD, Galson DL. TBK1 mediates critical effects of measles virus nucleocapsid protein (MVNP) on Pagetic osteoclast formation. J Bone Miner Res. 2014 Jan;29(1):90-102. PubMed Link
  • Wang FM, Sarmasik A, Hiruma Y, Sun Q, Sammut B, Windle JJ, Roodman GD, Galson DL. Measles virus nucleocapsid protein, a key contributor to Paget's disease, increases IL-6 expression via down-regulation of FoxO3/Sirt1 signaling. Bone. 2013 Mar;53(1):269-76. PubMed Link
  • D'Souza S, Kurihara N, Shiozawa Y, Joseph J, Taichman R, Galson DL, Roodman GD. Annexin II interactions with the annexin II receptor enhance multiple myeloma cell adhesion and growth in the bone marrow microenvironment. Blood. 2012 Feb 23;119(8):1888-96. PubMed Link
  • Galson DL, Silbermann R, Roodman GD. Mechanisms of multiple myeloma bone disease. Bonekey Rep. 2012 Aug 1;1:135. PubMed Link
  • D'Souza S, del Prete D, Jin S, Sun Q, Huston AJ, Kostov FE, Sammut B, Hong CS, Anderson JL, Patrene KD, Yu S, Velu CS, Xiao G, Grimes HL, Roodman GD, Galson DL. Gfi1 expressed in bone marrow stromal cells is a novel osteoblast suppressor in patients with multiple myeloma bone disease. Blood. 2011 Dec 22;118(26):6871-80. PubMed Link
  • Wang FM, Galson DL, Roodman GD, Ouyang H. Resveratrol triggers the pro-apoptotic endoplasmic reticulum stress response and represses pro-survival XBP1 signaling in human multiple myeloma cells. Exp Hematol. 2011 Oct;39(10):999-1006. PubMed Link
  • Li S, Pal R, Monaghan SA, Schafer P, Ouyang H, Mapara M, Galson DL, Lentzsch S. IMiD immunomodulatory compounds block C/EBPbeta translation through eIF4E down-regulation resulting in inhibition of MM. Blood. 2011 May 12;117(19):5157-65. PubMed Link
  • Pal R, Janz M, Galson DL, Gries M, Li S, Johrens K, Anagnostopoulos I, Dorken B, Mapara MY, Borghesi L, Kardava L, Roodman GD, Milcarek C, Lentzsch S. C/EBPbeta regulates transcription factors critical for proliferation and survival of multiple myeloma cells. Blood. 2009 Oct 29;114(18):3890-8. PubMed Link
  • Lu Y, Wang J, Xu Y, Koch AE, Cai Z, Chen X, Galson DL, Taichman RS, Zhang J. CXCL16 functions as a novel chemotactic factor for prostate cancer cells in vitro. Mol Cancer Res. 2008 Apr;6(4):546-54. PubMed Link
  • Lu Y, Xiao G, Galson DL, Nishio Y, Mizokami A, Keller ET, Yao Z, Zhang J. PTHrP-induced MCP-1 production by human bone marrow endothelial cells and osteoblasts promotes osteoclast differentiation and prostate cancer cell proliferation and invasion in vitro. Int J Cancer. 2007 Aug 15;121(4):724-33. PubMed Link

See all pubs (Pubmed)

Collaborations

Collaborations

Current Internal Collaborators

Steffi Oesterreich, PhD
Professor of Pharmacology and Chemical Biology
Member - Breast and Ovarian Cancer Program (BOCP)

Hongjiao Ouyang, DDS, PhD, DMD
Assistant Professor of Oral Biology
Member - Molecular and Cellular Cancer Biology Program (MCCBP)

Kostas Verdelis, DDS, PhD
Assistant Professor of Restorative Dentistry/Comprehensive Care

Current External Collaborators

G. David Roodman, MD, PhD
Kenneth Wiseman Professor of Medicine
Dept. of Medicine, Indiana University

Shared Resource Usage

Shared Resource Usage

  • Cell and Tissue Imaging Facility
  • Cytometry Facility

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Last modified: 8/5/14