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VANDERBILT UNIVERSITY MEDICAL CENTER

Center for Bone Biology

Current Team:
 

  • Denise Buenrostro, Graduate Student
  • Shellese Cannonier, Graduate Student
  • Ushashi Dadwal, Graduate Student
  • Alyssa Merkel, Research Assistant

 

Julie A. Sterling, Ph.D.
Medical College of Ohio, 2003

Assistant Professor
Medicine/Clinical Pharmacology and Cancer Biology

Phone:  (615) 322-4364
Fax:  (615) 343-2611
Email:  julie.sterling@vanderbilt.edu

Introduction:

The skeleton is a common site of metastasis in patients with advanced breast, prostate, and lung cancer. While we study each of these tumors to some degree, our laboratory focuses primarily on breast cancer metastasis to bone.    Once established in the skeleton, breast tumors have catastrophic effects on the skeleton inducing a vicious cycle in which tumor produced factors stimulate bone resorption resulting in the release of growth factors from the bone that further stimulate tumor growth and bone destruction. Our previous data have indicated that TGF-β, Gli2 (a transcription factor), and parathyroid hormone-related protein play important roles in the regulation of tumor-induced bone disease.

Research Interests:

* Regulation of Gli2 and PTHrP expression in bone
* Regulation of tumor-induced bone destruction by rigidity
* Pre-clinical testing of inhibitors for bone disease
* Imaging early stages of tumor-induced bone disease
* Microenvironmental regulation of tumor-induced bone disease

Research Techniques:

 

* Molecular Biology

      o Promoter studies
      o Transfections
      o Real-time PCR
      o Western Blots

* Animal models of bone metastasis

      o Intracardiac
      o Intratibial
      o Intravenous
      o Mammary fat pad
      o Subcutaneous

* Small Animal Imaging

      o Fluorescence
      o Micro-CT
      o Micro-SPECT
      o Micro-PET
      o X-ray
      o Histology

Current Research Support:
 

  • The Role of Mechanotransduction in Progression of Tumor-induced Bone Disease (1R01CA163499)
  • Strategies for early treatment of bone metastases. VA Merit (1I01BX001957)
  • In Vivo Cellular and Molecular Imaging Center Pilot Grant
  • The Effect of the Tumor Microenvironment on Cancer Metastasis to Bone: VA Career Development Award
  • Effects of Tumors on the Skeleton. Program Project Grant (5P01 CA40035).  PI- Elefteriou.
     

Publications:
 

  1. Johnson RW and Sterling JA. Metastatic Tumors to Bone in C.J Rosen (ed): Primer on the Metabolic Diseases and Disorders of Mineral Metabolism (8th Edition). Chapter 83. John Wiley and Sons, Inc. 2013.
  2. Danilin S, Merkel AR, Johnson JR, Johnson RW, Edwards JR, Sterling JA.  “Myeloid-derived suppressor cells expand during breast cancer progression and promote tumor-induced bone destruction”.  OncoImmunology 1 (2012).  *Cover Picture.
  3. Campbell JP, Karolak M, Ma Y, Perrien DS, S., Masood-Campbell SK, Penner NL, Munoz SA, Zijlstra A, Yang X, Sterling JA, Elefteriou F.  Stimulation of Host Bone Marrow Stromal Cells by Sympathetic Nerves Promotes Breast Cancer Bone Metastasis in Mice.  PLoSBiology 10 (2012).
  4. Campbell, JP, Masood SK, Merkel AR, Elefteriou F, and Sterling JA.  Models of Bone Metastasis.  JoVE (2012).
  5. Li X, Sterling JA, Fan KH, Vessella RL, Shyr Y, Hayward SW, Matrisian LM, Bhowmick NA.  Loss of TGF-β Responsiveness in Prostate Stromal Cells Alters Chemokine Levels and Facilitates the Development of Mixed Osteoblastic/Osteolytic Bone Lesions. Mol Cancer Res. (2012) PMCID – Journal in Process.  *Featured on the cover and in the highlights section.
  6. Biswas S, Nyman JS, Alvarez J, Chakrabarti A, Ayres A, Sterling J, Edwards J, Rana T, Johnson R, Perrien DS, Lonning S, Shyr Y, Matrisian LM, Mundy GR.  Anti-transforming growth factor ß antibody treatment rescues bone loss and prevents breast cancer metastasis to bone. PLOS One 6 (2011) e27090. PMCID: PMC3214031.
  7. Johnson RW, Merkel AR, Danilin S, Nguyen MP, Mundy GR, Sterling JA. 6-Thioguanine Inhibition of Parathyroid Hormone-related Protein Expression Is Mediated by GLI2.  Anticancer Research 31 (2011).
  8. Sterling JA and Johnson RW. Emerging Imaging Techniques for the Detection and Examination of Breast Cancer Metastasis to Bone.  In H.S. Watanabe (ed): Horizons in Cancer Research (Volume 46).  Chapter VIII. Nova Science Publishers.  Hauppauge, NY, 2011.
  9. Johnson RW, Nguyen MP, Padalecki SS, Grubbs BG,  Merkel AR, Oyajobi BO,  Matrisian LM, Mundy GR, Sterling JA. TGF-β promotion of Gli2 induced PTHrP expression is independent of canonical Hedgehog signaling. Cancer Research 71 (2011).  PMCID: PMC3077118.
  10. Guelcher SA and Sterling JA. Contribution of bone tissue modulus to breast cancer metastasis to bone. Cancer microenvironment. 2011
  11. Sterling JA, Guelcher SA.  Bone Structural Components Regulating Sites of Tumor Metastasis. Curr Osteoporos Rep. 2011.
  12. Johnson LC*, Johnson RW*, Munoz SA, Mundy GR, Peterson TE, Sterling JA. Longitudinal live animal microCT allows for quantitative analysis of tumor-induced bone destruction. Bone 48 (2011). 141-151. PMCID: PMC2974944. *Featured on the cover
  13. Sterling JA, Edwards JR, Martin TJ, Mundy GR. Advances in the biology of bone metastasis: How the skeleton affects tumor behavior. Bone 48 (2011). 6-15. PMCID Applied for.
  14. Ruppender NS, Merkel AR, Martin TJ, Mundy GR, Sterling JA, Guelcher SA.  Matrix Rigidity Induces Osteolytic Gene Expression of Metastatic Breast Cancer Cells.  PLoSONE 5 (2010).  PMCID: PMC2981576.
  15. Mundy GR and Sterling JA.  Metastatic Solid Tumors to Bone.  In C.J. Rosen, J.E.Comspston, J.B. Lian (eds): Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism (7th edition). Section VII, chapter 78.  American Society for Bone and Mineral Research, Washington, DC, 2008.
  16. Mundy GR, Edwards CM, Edwards JR, Lynch CC, Sterling JA, Zhuang J.  Localized Osteolysis. In J.P. Bilezikian, L.G. Raisz, T.J Martin (eds): Principles of Bone Biology (3rd edition). Volume 1, chapter 64.  Elsevier, Inc., St. Louis, MO, 2008.
  17. Mundy GR, Oyajobi BO, Gutierrez G, Sterling J, Padalecki S, Elefteriou F, Zhao M.  Cytokines and bone remodeling.  In Marcus, R, D Feldman, D Nelson, CJ Rosen (eds): Osteoporosis (3rd edition), Volume 1, Chapter 13.  Academic Press, Inc., San Diego, CA, 2007.
  18. Mundy GR, Oyajobi BO, Padalecki SS, Sterling JA.  Hypercalcemia of malignancy.  In Hay, I, H Turner, J Wass, (eds): Clinical Endocrine Oncology (2nd edition), Chapter .  Blackwell Publishing, Inc., London,   2007.
  19. Sterling JA, Oyajobi BO, Grubbs BG, Padalecki SS, Gupta A, Story B, S Munoz, Zhao M, and Mundy GR.  The Hedgehog Signaling Molecule Gli2 Induces PTHrP Expression and Osteolysis In Metastatic Human Breast Cancer Cells.  Cancer Research 66 (2006).
  20. Sterling JA, Wu L, and Banerji SS. PARP regulates TGF-beta receptor type II expression in estrogen receptor-positive breast cancer cell lines. Anticancer Research 26 (2006). 1893-1901.


Recent Abstracts:
 

  1. Cannonier S, Gonazales CB, Page JM, Merkel AR, Guelcher SA, Sterling JA.  Bone Rigidity Regulates Invasive Oral Squamous Cell Carcinoma Gene Expression. International Bone and Mineral Society: 2012 Cancer Induced Bone Disease Meeting.  Lyon, France. Nov. 2012. Poster Presentation
  2. Seeley EH, Wilson K, Johson RW, Caprioli RM, Matrisian LM, Sterling JA. MALDI IMS identifies protein signatures that vary between normal and tumor-bearing bone. International Bone and Mineral Society: 2012 Cancer Induced Bone Disease Meeting.  Lyon, France. Nov. 2012. Poster Presentation.
  3. Page J, Merkel AR, Guelcher SA, Sterling JA.  3D Polyurethane Scaffolds (3D-PURS) with Defined Architecture and Rigidity for Analysis of Tumor-induced Bone Disease.  International Bone and Mineral Society: 2012 Cancer Induced Bone Disease Meeting.  Lyon, France. Nov. 2012. Poster Presentation.
  4. Li X, Nyman J, Merkel A, Fan, K, Bhowmick N, Matrisian L, Sterling J.  Breast Cancer-induced Osteolytic Bone Lesions are Inhibited by TGF-β Signaling in Osteoclasts, but not Inhibited when Targeted to Osteoblasts.  American Society for Bone and Mineral Research 2012 Annual Meeting.  Minneapolis, MN. October, 2012.  Oral Presentation.
  5. Bi X, Sterling J, Rowland B, Perrien D, Nyman J, Elefteriou F, Mahadevan-Jansen A.  Characterization of the Alterations in Bone Composition Caused by Prostate Cancer Bone Metastasis Using Raman Spectroscopy.  American Society for Bone and Mineral Research 2012 Annual Meeting.  Minneapolis, MN. October, 2012.  Poster Presentation.
  6. Danilin S, Johnson R, Sterling J. Myeloid-Derived Suppressor Cells Promote Breast Cancer-Induced Bone Destruction. American Society for Bone and Mineral Research 2012 Annual Meeting.  Minneapolis, MN. October, 2012.  Poster Presentation.
  7. Gonzales C, Merkel A, Cannonier S, Sterling J. Regulation of PTHrP Expression in Bone Invasive Oral Squamous Cell Carcinomas. American Society for Bone and Mineral Research 2012 Annual Meeting.  Minneapolis, MN. October, 2012.  Poster Presentation.
  8. Campbell JP, Karolak MR, Masood S, Perrien D, Sterling J, Elefteriou F. ß2AR Stimulation of Host Osteoblasts Promotes Breast Cancer Bone Metastasis via RANKL. American Society for Bone and Mineral Research 2012 Annual Meeting.  Minneapolis, MN. October, 2012.  Poster Presentation.
  9. Makowski A, Uppuganti S, Rowland B, Merkel A, Perrien D, Sterling J, Nyman J.TGF-β Suppression with a Neutralizing Antibody Increases Vertebral Body Strength in Female Mice. American Society for Bone and Mineral Research 2012 Annual Meeting.  Minneapolis, MN. October, 2012.  Poster Presentation.
  10. Smith RA, Merkel AR, Johnson RW, Manning HC, Sterling JA.  Novel TSPO PET Imaging Probes for Early Detection of Tumors in Bone.  International Bone and Mineral Society: 2011 Cancer Induced Bone Disease Meeting.  Chicago, IL. Nov. 2011.  Oral Presentation.
  11. Ruppender NS, Merkel AR, Guelcher SA, Sterling JA. Integrin Dependent Mechanotransduction Signaling Regulates PTHrP Expression in Breast Cancer Cells.  International Bone and Mineral Society: 2011 Cancer Induced Bone Disease Meeting.  Chicago, IL. Nov. 2011.
  12. Johnson RW, Merkel AR, Ruppender NS, Guelcher SA, Matrisian LM, Sterling JA.   Bone stiffness drives Wnt signaling regulation of Gli2 in osteolytic breast cancer cells.  International Bone and Mineral Society: 2011 Cancer Induced Bone Disease Meeting.  Chicago, IL. Nov. 2011.  Oral Presentation.
  13. Nyman JS, Merkel AR, Rowland BJ, Esparza JM, Makowski AJ, and Sterling JA. The Effect of TGFb Suppression on Bone Quality and Tumor Burden in Two Mouse Models of Multiple Myeloma.  International Bone and Mineral Society: 2011 Cancer Induced Bone Disease Meeting.  Chicago, IL. Nov. 2011.
  14. Ruppender NS, Merkel AR, Guelcher SA, Sterling JA.  The Mechanotransduction Pathway Regulates Tumor Response to Rigidity and PTHrP Expression.  33rd Annual American Society for Bone and Mineral Research Meeting. San Diego, CA. 15-20 September 2011.
  15. Johnson RW, Nguyen, S. Padalecki, B. Grubbs, A.R. Merkel, B. Oyajobi, G.R. Mundy, J.A. Sterling. TGF-β Promotion of Gli2 Induced PTHrP Expression is Independent off Canonical Hedgehog Signaling. 10th International Conference Cancer Induced Bone Disease.  22-25 September 2010.  Sheffield, UK. Oral Communication.
  16. Ruppender NS, Sterling JA, Martin TJ, Mundy GR, Guelcher SA.  Skeletal Rigidity Enhances TGF-β Effects on Cancer Cell Expression of Osteolytic Factors.  10th International Conference Cancer Induced Bone Disease.  22-25 September 2010.  Sheffield, UK.  Poster Presentation.
  17. Danilin S, Sterling JA, Merkel AR, Johnson J, Johnson RW, Edwards JR, Mundy GR. Myeloid-Derived Suppressor Cells Expand During Breast Cancer Progression and Promote Tumor-induced Bone Destruction. 32nd Annual American Society for Bone and Mineral Research Meeting. Toronto, ON, Canada. 2010.  Oral Presentation.
  18. Johnson RW, Nguyen MP, Padalecki SS, Grubbs B, Merkel AR, Oyajobi BO, Mundy GR, J.A. Sterling. Targeted Inhibition of GLI2 Blocks Cancer Bone Disease in Vivo. 32nd Annual American Society for Bone and Mineral Research Meeting. Toronto, ON, Canada. 2010.
  19. Johnson RW, Johnson LC, Nolting D, Munoz SA, Mundy GR, Manning HC, Peterson T, Sterling JA, Combined In Vivo MicroCT and Near-Infrared Imaging Allows for Quantitative Analyses of the Tumor Microenvironment. 32nd Annual American Society for Bone and Mineral Research Meeting. Toronto, ON, Canada. 2010.
  20. Campbell JP, Sterling JA, Mundy GR, Elefteriou F.  Sympathetic Nervous System Activation Increases Breast Cancer Metastasis to Bone. 32nd Annual American Society for Bone and Mineral Research Meeting. Toronto, ON, Canada.  2010.  Oral Presentation.

This page was last updated April 10, 2013 and is maintained by Center for Bone Biology