Our research focuses on tumors that metastasize to bone and the subsequent changes in bone that occur. While our research focuses primarily on breast cancer metastasis to bone, we also study lung, prostate, and myeloma which are tumors that can reside in bone and induce bone disease. Once breast tumors establish in bone they can stimulate bone destructions, which leads to increased fracture rates and pain in patients. Importantly, there are no cures for tumors once they have established in bone. We study the mechanisms that regulate metasis to bone and induce bone destruction, which requires molecular biology, engineering, animal models, and small animal imaging. These techniques together have helped us better understand tumor-induced bone disease and have allowed us to begin testing promising therapeutics in small animal models of tumor-induced bone disease.

Specifically, we have determined that the developmental transcription factor Gli2 is upreguated when tumor cells metastasize to bone and that this leads to the production of the the osteolytic (bone destructive) factor parathyroid hormone related protein (PTHrP). While it is still unclear why Gli2 is expressed in some tumor cells, our work has demonstrated that the physical stiffness of bone stimulates Gli2 and PTHrP expression through a combination of transforming growth factor-beta and mechanotransduction signaling. Currently we are testing the applicability of inhibitors to these pathways to determine their efficacy in our pre-clinical models of cancer metastasis to bone.


The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Tuning Ligand Density To Optimize Pharmacokinetics of Targeted Nanoparticles for Dual Protection against Tumor-Induced Bone Destruction. Vanderburgh J, Hill JL, Gupta MK, Kwakwa KA, Wang SK, Moyer K, Bedingfield SK, Merkel AR, d'Arcy R, Guelcher SA, Rhoades JA, Duvall CL (2020) ACS Nano 14(1): 311-327
    › Primary publication · 31894963 (PubMed) · PMC7216559 (PubMed Central)
  2. Systemic delivery of a Gli inhibitor via polymeric nanocarriers inhibits tumor-induced bone disease. Vanderburgh JP, Kwakwa KA, Werfel TA, Merkel AR, Gupta MK, Johnson RW, Guelcher SA, Duvall CL, Rhoades JA (2019) J Control Release : 257-272
    › Primary publication · 31494183 (PubMed) · PMC7007697 (PubMed Central)
  3. Early TGF-β inhibition in mice reduces the incidence of breast cancer induced bone disease in a myeloid dependent manner. Buenrostro D, Kwakwa KA, Putnam NE, Merkel AR, Johnson JR, Cassat JE, Sterling JA (2018) Bone : 77-88
    › Primary publication · 29753718 (PubMed) · PMC6118216 (PubMed Central)
  4. Skeletal Colonization by Breast Cancer Cells Is Stimulated by an Osteoblast and β2AR-Dependent Neo-Angiogenic Switch. Mulcrone PL, Campbell JP, Clément-Demange L, Anbinder AL, Merkel AR, Brekken RA, Sterling JA, Elefteriou F (2017) J Bone Miner Res 32(7): 1442-1454
    › Primary publication · 28300321 (PubMed) · PMC5489363 (PubMed Central)
  5. Murine models of breast cancer bone metastasis. Wright LE, Ottewell PD, Rucci N, Peyruchaud O, Pagnotti GM, Chiechi A, Buijs JT, Sterling JA (2016) Bonekey Rep : 804
    › Primary publication · 27867497 (PubMed) · PMC5108088 (PubMed Central)
  6. Tissue-engineered 3D cancer-in-bone modeling: silk and PUR protocols. Dadwal U, Falank C, Fairfield H, Linehan S, Rosen CJ, Kaplan DL, Sterling J, Reagan MR (2016) Bonekey Rep : 842
    › Primary publication · 27790370 (PubMed) · PMC5070496 (PubMed Central)
  7. Hedgehog and TGFβ signaling converge on Gli2 to control bony invasion and bone destruction in oral squamous cell carcinoma. Cannonier SA, Gonzales CB, Ely K, Guelcher SA, Sterling JA (2016) Oncotarget 7(46): 76062-76075
    › Primary publication · 27738315 (PubMed) · PMC5340177 (PubMed Central)
  8. Substrate Modulus Regulates Osteogenic Differentiation of Rat Mesenchymal Stem Cells through Integrin β1 and BMP Receptor Type IA. Guo R, Lu S, Merkel AR, Sterling JA, Guelcher SA (2016) J Mater Chem B 4(20): 3584-3593
    › Primary publication · 27551426 (PubMed) · PMC4991780 (PubMed Central)
  9. Combined treatment with a transforming growth factor beta inhibitor (1D11) and bortezomib improves bone architecture in a mouse model of myeloma-induced bone disease. Nyman JS, Merkel AR, Uppuganti S, Nayak B, Rowland B, Makowski AJ, Oyajobi BO, Sterling JA (2016) Bone : 81-91
    › Primary publication · 27423464 (PubMed) · PMC4996753 (PubMed Central)
  10. 3D Printing of Tissue Engineered Constructs for In Vitro Modeling of Disease Progression and Drug Screening. Vanderburgh J, Sterling JA, Guelcher SA (2017) Ann Biomed Eng 45(1): 164-179
    › Primary publication · 27169894 (PubMed) · PMC5106334 (PubMed Central)
  11. Substrate modulus of 3D-printed scaffolds regulates the regenerative response in subcutaneous implants through the macrophage phenotype and Wnt signaling. Guo R, Merkel AR, Sterling JA, Davidson JM, Guelcher SA (2015) Biomaterials : 85-95
    › Primary publication · 26406449 (PubMed) · PMC4846647 (PubMed Central)
  12. The Role of Hedgehog Signaling in Tumor Induced Bone Disease. Cannonier SA, Sterling JA (2015) Cancers (Basel) 7(3): 1658-83
    › Primary publication · 26343726 (PubMed) · PMC4586789 (PubMed Central)
  13. Altering adsorbed proteins or cellular gene expression in bone-metastatic cancer cells affects PTHrP and Gli2 without altering cell growth. Page JM, Merkel AR, Ruppender NS, Guo R, Dadwal UC, Cannonier S, Basu S, Guelcher SA, Sterling JA (2015) Data Brief : 440-6
    › Primary publication · 26306316 (PubMed) · PMC4534584 (PubMed Central)
  14. TRIzol and Alu qPCR-based quantification of metastatic seeding within the skeleton. Preston Campbell J, Mulcrone P, Masood SK, Karolak M, Merkel A, Hebron K, Zijlstra A, Sterling J, Elefteriou F (2015) Sci Rep : 12635
    › Primary publication · 26271202 (PubMed) · PMC4536516 (PubMed Central)
  15. Fabrication of 3D Scaffolds with Precisely Controlled Substrate Modulus and Pore Size by Templated-Fused Deposition Modeling to Direct Osteogenic Differentiation. Guo R, Lu S, Page JM, Merkel AR, Basu S, Sterling JA, Guelcher SA (2015) Adv Healthc Mater 4(12): 1826-32
    › Primary publication · 26121662 (PubMed) · PMC4558627 (PubMed Central)
  16. Matrix rigidity regulates the transition of tumor cells to a bone-destructive phenotype through integrin β3 and TGF-β receptor type II. Page JM, Merkel AR, Ruppender NS, Guo R, Dadwal UC, Cannonier S, Basu S, Guelcher SA, Sterling JA (2015) Biomaterials : 33-44
    › Primary publication · 26115412 (PubMed) · PMC4681301 (PubMed Central)
  17. Predicting mouse vertebra strength with micro-computed tomography-derived finite element analysis. Nyman JS, Uppuganti S, Makowski AJ, Rowland BJ, Merkel AR, Sterling JA, Bredbenner TL, Perrien DS (2015) Bonekey Rep : 664
    › Primary publication · 25908967 (PubMed) · PMC4407510 (PubMed Central)
  18. Addressing the controversy: do bisphosphonates directly affect primary tumors? Sterling JA (2015) Cancer Discov 5(1): 14-5
    › Primary publication · 25583797 (PubMed) · PMC4295645 (PubMed Central)
  19. Wnt signaling induces gene expression of factors associated with bone destruction in lung and breast cancer. Johnson RW, Merkel AR, Page JM, Ruppender NS, Guelcher SA, Sterling JA (2014) Clin Exp Metastasis 31(8): 945-59
    › Primary publication · 25359619 (PubMed) · PMC4258192 (PubMed Central)
  20. Development of Raman spectral markers to assess metastatic bone in breast cancer. Ding H, Nyman JS, Sterling JA, Perrien DS, Mahadevan-Jansen A, Bi X (2014) J Biomed Opt 19(11): 111606
    › Primary publication · 24933683 (PubMed) · PMC4059340 (PubMed Central)
  21. Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease. Seeley EH, Wilson KJ, Yankeelov TE, Johnson RW, Gore JC, Caprioli RM, Matrisian LM, Sterling JA (2014) Bone : 208-16
    › Primary publication · 24487126 (PubMed) · PMC4005328 (PubMed Central)
  22. Biomaterial scaffolds for treating osteoporotic bone. Sterling JA, Guelcher SA (2014) Curr Osteoporos Rep 12(1): 48-54
    › Primary publication · 24458428 (PubMed) · PMC4048367 (PubMed Central)
  23. ALCAM/CD166 is a TGF-β-responsive marker and functional regulator of prostate cancer metastasis to bone. Hansen AG, Arnold SA, Jiang M, Palmer TD, Ketova T, Merkel A, Pickup M, Samaras S, Shyr Y, Moses HL, Hayward SW, Sterling JA, Zijlstra A (2014) Cancer Res 74(5): 1404-15
    › Primary publication · 24385212 (PubMed) · PMC4149913 (PubMed Central)
  24. 6-Thioguanine inhibition of parathyroid hormone-related protein expression is mediated by GLI2. Johnson RW, Merkel AR, Danilin S, Nguyen MP, Mundy GR, Sterling JA (2011) Anticancer Res 31(9): 2705-12
    › Primary publication · 21868511 (PubMed) · PMC3430074 (PubMed Central)