Julie Anne Sterling, Ph.D.

Assistant Professor

julie.sterling@vanderbilt.edu

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Faculty Appointments
Assistant Professor of Medicine Assistant Professor of Biomedical EngineeringAssistant Professor of Cancer Biology
Education
Ph.D., Molecular and Cellular Biology, Medical College of Ohio, Toledo, OhioB.S., Microbiology, Bowling Green State University, Bowling Green, Ohio
Office Address
1225C MRB IV
TN 0575
Research Description
Our research focuses tumors (including breast, prostate, lung, myeloma, oral cancer, and others) that metastasize or invade into the bone and induce subsequent changes in the bone that lead to increased fracture rates and pain in patients. Unfortunately, there are no cures for tumors once they have established in bone. We study the mechanisms that regulate tumor establishment in bone and bone destruction, which requires a blend of molecular biology, engineering, and pre-clinical models. 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, our previous studies have demonstrated that the expression of Gli2, a transcription factor, is strongly correlated with tumor cells that induce bone destruction. We have further shown that the physical and cellular components of the bone and bone marrow can alter gene expression and tumor behavior. Our current work is further exploring how complex interactions with the bone/bone marrow contribute to disease, and have begun testing inhibitor of signaling pathways important for tumor interactions with the bone microenvironment.
Research Keywords
Cancer metastasis to bone and tumor-induced bone disease.
Publications
Buenrostro D, Mulcrone PL, Owens P, Sterling JA. The Bone Microenvironment: a Fertile Soil for Tumor Growth. Curr Osteoporos Rep. 2016 Aug; 14(4): 151-8. PMID: 27255469, PMCID: PMC4927340, PII: 10.1007/s11914-016-0315-2, DOI: 10.1007/s11914-016-0315-2, ISSN: 1544-2241.

Nyman JS, Merkel AR, Uppuganti S, Nayak B, Rowland B, Makowski AJ, Oyajobi BO, Sterling JA. Combined treatment with a transforming growth factor beta inhibitor (1D11) and bortezomib improves bone architecture in a mouse model of myeloma-induced bone disease. Bone [print-electronic]. 2016 Jul 7/13/2016; PMID: 27423464, PII: S8756-3282(16)30187-9, DOI: 10.1016/j.bone.2016.07.007, ISSN: 1873-2763.

Vanderburgh J, Sterling JA, Guelcher SA. 3D Printing of Tissue Engineered Constructs for In Vitro Modeling of Disease Progression and Drug Screening. Ann Biomed Eng [print-electronic]. 2016 May 5/11/2016; PMID: 27169894, PII: 10.1007/s10439-016-1640-4, DOI: 10.1007/s10439-016-1640-4, ISSN: 1573-9686.

Guo R, Merkel AR, Sterling JA, Davidson JM, Guelcher SA. Substrate modulus of 3D-printed scaffolds regulates the regenerative response in subcutaneous implants through the macrophage phenotype and Wnt signaling. Biomaterials [print-electronic]. 2015 Dec; 73: 85-95. PMID: 26406449, PMCID: PMC4846647, PII: S0142-9612(15)00750-4, DOI: 10.1016/j.biomaterials.2015.09.005, ISSN: 1878-5905.

Page JM, Merkel AR, Ruppender NS, Guo R, Dadwal UC, Cannonier S, Basu S, Guelcher SA, Sterling JA. Altering adsorbed proteins or cellular gene expression in bone-metastatic cancer cells affects PTHrP and Gli2 without altering cell growth. Data Brief. 2015 Sep; 4: 440-6. PMID: 26306316, PMCID: PMC4534584, PII: S2352-3409(15)00122-5, DOI: 10.1016/j.dib.2015.07.003, ISSN: 2352-3409.

Page JM, Merkel AR, Ruppender NS, Guo R, Dadwal UC, Cannonier SA, Basu S, Guelcher SA, Sterling JA. Matrix rigidity regulates the transition of tumor cells to a bone-destructive phenotype through integrin ß3 and TGF-ß receptor type II. Biomaterials [print-electronic]. 2015 Sep; 64: 33-44. PMID: 26115412, PMCID: PMC4681301, PII: S0142-9612(15)00540-2, DOI: 10.1016/j.biomaterials.2015.06.026, ISSN: 1878-5905.

Guo R, Lu S, Page JM, Merkel AR, Basu S, Sterling JA, Guelcher SA. Fabrication of 3D Scaffolds with Precisely Controlled Substrate Modulus and Pore Size by Templated-Fused Deposition Modeling to Direct Osteogenic Differentiation. Adv Healthc Mater [print-electronic]. 2015 Aug 8/26/2015; 4(12): 1826-32. PMID: 26121662, PMCID: PMC4558627, DOI: 10.1002/adhm.201500099, ISSN: 2192-2659.

Cannonier SA, Sterling JA. The Role of Hedgehog Signaling in Tumor Induced Bone Disease. Cancers (Basel). 2015; 7(3): 1658-83. PMID: 26343726, PMCID: PMC4586789, PII: cancers7030856, DOI: 10.3390/cancers7030856, ISSN: 2072-6694.

Nyman JS, Uppuganti S, Makowski AJ, Rowland BJ, Merkel AR, Sterling JA, Bredbenner TL, Perrien DS. Predicting mouse vertebra strength with micro-computed tomography-derived finite element analysis. Bonekey Rep. 2015; 4: 664. PMID: 25908967, PMCID: PMC4407510, DOI: 10.1038/bonekey.2015.31, ISSN: 2047-6396.

Sterling JA. Addressing the controversy: do bisphosphonates directly affect primary tumors?. Cancer Discov. 2015 Jan; 5(1): 14-5. PMID: 25583797, PMCID: PMC4295645, PII: 5/1/14, DOI: 10.1158/2159-8290.CD-14-1380, ISSN: 2159-8290.

Preston Campbell J, Mulcrone P, Masood SK, Karolak M, Merkel A, Hebron K, Zijlstra A, Sterling J, Elefteriou F. TRIzol and Alu qPCR-based quantification of metastatic seeding within the skeleton. Sci Rep. 2015; 5: 12635. PMID: 26271202, PMCID: PMC4536516, PII: srep12635, DOI: 10.1038/srep12635, ISSN: 2045-2322.

Seeley EH, Wilson KJ, Yankeelov TE, Johnson RW, Gore JC, Caprioli RM, Matrisian LM, Sterling JA. Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease. Bone [print-electronic]. 2014 Apr; 61: 208-16. PMID: 24487126, PMCID: PMC4005328, PII: S8756-3282(14)00019-2, DOI: 10.1016/j.bone.2014.01.017, ISSN: 1873-2763.

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. ALCAM/CD166 is a TGF-ß-responsive marker and functional regulator of prostate cancer metastasis to bone. Cancer Res [print-electronic]. 2014 Mar 3/1/2014; 74(5): 1404-15. PMID: 24385212, PMCID: PMC4149913, PII: 0008-5472.CAN-13-1296, DOI: 10.1158/0008-5472.CAN-13-1296, ISSN: 1538-7445.

Buenrostro D, Park SI, Sterling JA. Dissecting the role of bone marrow stromal cells on bone metastases. Biomed Res Int [print-electronic]. 2014; 2014: 875305. PMID: 25054153, PMCID: PMC4099112, DOI: 10.1155/2014/875305, ISSN: 2314-6141.

Ding H, Nyman JS, Sterling JA, Perrien DS, Mahadevan-Jansen A, Bi X. Development of Raman spectral markers to assess metastatic bone in breast cancer. J Biomed Opt. 2014; 19(11): 111606. PMID: 24933683, PMCID: PMC4059340, PII: 1882987, DOI: 10.1117/1.JBO.19.11.111606, ISSN: 1560-2281.

Bi X, Sterling JA, Merkel AR, Perrien DS, Nyman JS, Mahadevan-Jansen A. Prostate cancer metastases alter bone mineral and matrix composition independent of effects on bone architecture in mice--a quantitative study using microCT and Raman spectroscopy. Bone [print-electronic]. 2013 Oct; 56(2): 454-60. PMID: 23867219, PMCID: PMC3799839, PII: S8756-3282(13)00266-4, DOI: 10.1016/j.bone.2013.07.006, ISSN: 1873-2763.

Jin R, Sterling JA, Edwards JR, DeGraff DJ, Lee C, Park SI, Matusik RJ. Activation of NF-kappa B signaling promotes growth of prostate cancer cells in bone. PLoS ONE [print-electronic]. 2013; 8(4): e60983. PMID: 23577181, PMCID: PMC3618119, PII: PONE-D-12-24565, DOI: 10.1371/journal.pone.0060983, ISSN: 1932-6203.

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. 2012 Dec 12/1/2012; 1(9): 1484-94. PMID: 23264895, PMCID: PMC3525604, PII: 2012ONCOIMM0181, DOI: 10.4161/onci.21990, ISSN: 2162-4011.

Campbell JP, Karolak MR, Ma Y, Perrien DS, 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. PLoS Biol [print-electronic]. 2012 Jul; 10(7): e1001363. PMID: 22815651, PMCID: PMC3398959, PII: PBIOLOGY-D-12-00249, DOI: 10.1371/journal.pbio.1001363, ISSN: 1545-7885.

Li X, Sterling JA, Fan KH, Vessella RL, Shyr Y, Hayward SW, Matrisian LM, Bhowmick NA. Loss of TGF-ß responsiveness in prostate stromal cells alters chemokine levels and facilitates the development of mixed osteoblastic/osteolytic bone lesions. Mol. Cancer Res [print-electronic]. 2012 Apr; 10(4): 494-503. PMID: 22290877, PMCID: PMC3900026, PII: 1541-7786.MCR-11-0506, DOI: 10.1158/1541-7786.MCR-11-0506, ISSN: 1557-3125.

Campbell JP, Merkel AR, Masood-Campbell SK, Elefteriou F, Sterling JA. Models of bone metastasis. J Vis Exp. 2012; (67): e4260. PMID: 22972196, PMCID: PMC3490264, PII: 4260, DOI: 10.3791/4260, ISSN: 1940-087X.

Guelcher SA, Sterling JA. Contribution of bone tissue modulus to breast cancer metastasis to bone. Cancer Microenviron [print-electronic]. 2011 Dec; 4(3): 247-59. PMID: 21789687, PMCID: PMC3234324, DOI: 10.1007/s12307-011-0078-3, ISSN: 1875-2284.

Sterling JA, Guelcher SA. Bone structural components regulating sites of tumor metastasis. Curr Osteoporos Rep. 2011 Jun; 9(2): 89-95. PMID: 21424744, PMCID: PMC3430076, DOI: 10.1007/s11914-011-0052-5, ISSN: 1544-2241.

Johnson RW, Nguyen MP, Padalecki SS, Grubbs BG, Merkel AR, Oyajobi BO, Matrisian LM, Mundy GR, Sterling JA. TGF-beta promotion of Gli2-induced expression of parathyroid hormone-related protein, an important osteolytic factor in bone metastasis, is independent of canonical Hedgehog signaling. Cancer Res [print-electronic]. 2011 Feb 2/1/2011; 71(3): 822-31. PMID: 21189326, PMCID: PMC3077118, PII: 0008-5472.CAN-10-2993, DOI: 10.1158/0008-5472.CAN-10-2993, ISSN: 1538-7445.

Johnson LC, Johnson RW, Munoz SA, Mundy GR, Peterson TE, Sterling JA. Longitudinal live animal micro-CT allows for quantitative analysis of tumor-induced bone destruction. Bone [print-electronic]. 2011 Jan; 48(1): 141-51. PMID: 20685406, PMCID: PMC2974944, PII: S8756-3282(10)01284-6, DOI: 10.1016/j.bone.2010.05.033, ISSN: 1873-2763.

Sterling JA, Edwards JR, Martin TJ, Mundy GR. Advances in the biology of bone metastasis: how the skeleton affects tumor behavior. Bone [print-electronic]. 2011 Jan; 48(1): 6-15. PMID: 20643235, PII: S8756-3282(10)01358-X, DOI: 10.1016/j.bone.2010.07.015, ISSN: 1873-2763.

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 [print-electronic]. 2011; 6(11): e27090. PMID: 22096521, PMCID: PMC3214031, PII: PONE-D-11-14957, DOI: 10.1371/journal.pone.0027090, ISSN: 1932-6203.

Ruppender NS, Merkel AR, Martin TJ, Mundy GR, Sterling JA, Guelcher SA. Matrix rigidity induces osteolytic gene expression of metastatic breast cancer cells. PLoS ONE. 2010; 5(11): e15451. PMID: 21085597, PMCID: PMC2981576, DOI: 10.1371/journal.pone.0015451, ISSN: 1932-6203.

Sterling JA, Oyajobi BO, Grubbs B, Padalecki SS, Munoz SA, Gupta A, Story B, Zhao M, Mundy GR. The hedgehog signaling molecule Gli2 induces parathyroid hormone-related peptide expression and osteolysis in metastatic human breast cancer cells. Cancer Res. 2006 Aug 8/1/2006; 66(15): 7548-53. PMID: 16885353, PII: 66/15/7548, DOI: 10.1158/0008-5472.CAN-06-0452, ISSN: 0008-5472.

Sterling JA, Wu L, Banerji SS. PARP regulates TGF-beta receptor type II expression in estrogen receptor-positive breast cancer cell lines. Anticancer Res. 2006 May; 26(3A): 1893-901. PMID: 16827122, ISSN: 0250-7005.