Rachelle Whitney Johnson, Ph.D.

Assistant Professor

rachelle.johnson@vanderbilt.edu
Faculty Appointments
Assistant Professor of Medicine
Education
Ph.D., Cancer Biology, Vanderbilt University, Nashville, TennesseeB.S., Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia
Office Address
2215b Garland Ave
1165C Medical Research Building IV
Nashville, TN 37232
Research Description
The Johnson laboratory focuses on breast cancer metastasis to bone and breast cancer dormancy in bone, with an emphasis on the signaling pathways that mediate these processes. Improvement in the clinical care of patients with primary breast cancer has dramatically increased patient survival rates over the past decade, yet many patients still develop distant metastases that are strongly associated with increased morbidity and mortality. Recurrence arises from disseminated tumor cells that have overcome their dormant state and proliferate at the site of metastasis. We wish to gain a better understanding of how these dormant cells, which reside in the bone marrow, exit dormancy.

Our particular interest lies in the role of hypoxia (low oxygen tensions) and leukemia inhibitory factor (LIF) signaling in breast cancer colonization of the bone marrow, bone metastasis, and tumor cell entry/exit from dormancy. We use a combination of molecular and cell biology assays and xenograft and transgenic mouse models to study the mechanism by which breast cancer cells enter and exit a dormant state, and the impact of the bone microenvironment on this process.

Please visit the Johnson laboratory website for more information: https://www.vumc.org/vcbb/person/rachelle-w-johnson-phd
Research Keywords
Bone metastasis, breast cancer, hypoxia, leukemia inhibitory factor
Publications
Sowder ME, Johnson RW. Enrichment and detection of bone disseminated tumor cells in models of low tumor burden. Sci Rep. 2018 Sep 9/24/2018; 8(1): 14299. PMID: 30250146, PMCID: PMC6155169, PII: 10.1038/s41598-018-32653-2, DOI: 10.1038/s41598-018-32653-2, ISSN: 2045-2322.

Johnson RW, Suva LJ. Hallmarks of Bone Metastasis. Calcif. Tissue Int [print-electronic]. 2018 Feb; 102(2): 141-51. PMID: 29138883, PMCID: PMC5807131, PII: 10.1007/s00223-017-0362-4, DOI: 10.1007/s00223-017-0362-4, ISSN: 1432-0827.

Johnson RW, Sun Y, Ho PWM, Chan ASM, Johnson JA, Pavlos NJ, Sims NA, Martin TJ. Parathyroid Hormone-Related Protein Negatively Regulates Tumor Cell Dormancy Genes in a PTHR1/Cyclic AMP-Independent Manner. Front Endocrinol (Lausanne). 2018; 9: 241. PMID: 29867773, PMCID: PMC5964132, DOI: 10.3389/fendo.2018.00241, ISSN: 1664-2392.

Cho DC, Brennan HJ, Johnson RW, Poulton IJ, Gooi JH, Tonkin BA, McGregor NE, Walker EC, Handelsman DJ, Martin TJ, Sims NA. Bone corticalization requires local SOCS3 activity and is promoted by androgen action via interleukin-6. Nat Commun. 2017 Oct 10/9/2017; 8(1): 806. PMID: 28993616, PMCID: PMC5634449, PII: 10.1038/s41467-017-00920-x, DOI: 10.1038/s41467-017-00920-x, ISSN: 2041-1723.

Swami S, Johnson J, Bettinson LA, Kimura T, Zhu H, Albertelli MA, Johnson RW, Wu JY. Prevention of breast cancer skeletal metastases with parathyroid hormone. JCI Insight [print-electronic]. 2017 Sep 9/7/2017; 2(17): PMID: 28878134, PMCID: PMC5621896, PII: 90874, DOI: 10.1172/jci.insight.90874, ISSN: 2379-3708.

Johnson RW, Sowder ME, Giaccia AJ. Hypoxia and Bone Metastatic Disease. Curr Osteoporos Rep. 2017 Aug; 15(4): 231-8. PMID: 28597139, PII: 10.1007/s11914-017-0378-8, DOI: 10.1007/s11914-017-0378-8, ISSN: 1544-2241.

Johnson RW, Sowder ME, Giaccia AJ. Hypoxia and Bone Metastatic Disease. Curr Osteoporos Rep. 2017 Aug; 15(4): 231-8. PMID: 28597139, PMCID: PMC5667665, PII: 10.1007/s11914-017-0378-8, DOI: 10.1007/s11914-017-0378-8, ISSN: 1544-2241.

Johnson RW, Finger EC, Olcina MM, Vilalta M, Aguilera T, Miao Y, Merkel AR, Johnson JR, Sterling JA, Wu JY, Giaccia AJ. Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow. Nat. Cell Biol [print-electronic]. 2016 Sep 9/19/2016; 18(10): 1078-89. PMID: 27642788, PII: ncb3408, DOI: 10.1038/ncb3408, ISSN: 1476-4679.

Walker EC, Johnson RW, Hu Y, Brennan HJ, Poulton IJ, Zhang JG, Jenkins BJ, Smyth GK, Nicola NA, Sims NA. Murine Oncostatin M acts via Leukemia Inhibitory Factor Receptor to phosphorylate STAT3 but not STAT1, an effect that protects bone mass. J. Biol. Chem [print-electronic]. 2016 Aug 8/18/2016; PMID: 27539849, PII: M116.748483, DOI: 10.1074/jbc.M116.748483, ISSN: 1083-351X.

Bielanowicz A, Johnson RW, Goh H, Moody SC, Poulton IJ, Croce N, Loveland KL, Hedger MP, Sims NA, Itman C. Prepubertal Di-n-Butyl Phthalate Exposure Alters Sertoli and Leydig Cell Function and Lowers Bone Density in Adult Male Mice. Endocrinology [print-electronic]. 2016 Jul; 157(7): 2595-603. PMID: 27058814, DOI: 10.1210/en.2015-1936, ISSN: 1945-7170.

Johnson RW, McGregor NE, Brennan HJ, Crimeen-Irwin B, Poulton IJ, Martin TJ, Sims NA. Glycoprotein130 (Gp130)/interleukin-6 (IL-6) signalling in osteoclasts promotes bone formation in periosteal and trabecular bone. Bone [print-electronic]. 2015 Dec; 81: 343-51. PMID: 26255596, PII: S8756-3282(15)00316-6, DOI: 10.1016/j.bone.2015.08.005, ISSN: 1873-2763.

Johnson RW, Schipani E, Giaccia AJ. HIF targets in bone remodeling and metastatic disease. Pharmacol. Ther [print-electronic]. 2015 Jun; 150: 169-77. PMID: 25681658, PMCID: PMC4414805, PII: S0163-7258(15)00046-7, DOI: 10.1016/j.pharmthera.2015.02.002, ISSN: 1879-016X.

Johnson RW, Merkel AR, Page JM, Ruppender NS, Guelcher SA, Sterling JA. Wnt signaling induces gene expression of factors associated with bone destruction in lung and breast cancer. Clin. Exp. Metastasis [print-electronic]. 2014 Dec; 31(8): 945-59. PMID: 25359619, PMCID: PMC4258192, DOI: 10.1007/s10585-014-9682-1, ISSN: 1573-7276.

Standal T, Johnson RW, McGregor NE, Poulton IJ, Ho PW, Martin TJ, Sims NA. Gp130 in late osteoblasts and osteocytes is required for PTH-induced osteoblast differentiation. J. Endocrinol [print-electronic]. 2014 Nov; 223(2): 181-90. PMID: 25228504, PII: JOE-14-0424, DOI: 10.1530/JOE-14-0424, ISSN: 1479-6805.

Johnson RW, White JD, Walker EC, Martin TJ, Sims NA. Myokines (muscle-derived cytokines and chemokines) including ciliary neurotrophic factor (CNTF) inhibit osteoblast differentiation. Bone [print-electronic]. 2014 Jul; 64: 47-56. PMID: 24721701, PII: S8756-3282(14)00127-6, DOI: 10.1016/j.bone.2014.03.053, ISSN: 1873-2763.

Johnson RW, Brennan HJ, Vrahnas C, Poulton IJ, McGregor NE, Standal T, Walker EC, Koh TT, Nguyen H, Walsh NC, Forwood MR, Martin TJ, Sims NA. The primary function of gp130 signaling in osteoblasts is to maintain bone formation and strength, rather than promote osteoclast formation. J. Bone Miner. Res. 2014 Jun; 29(6): 1492-505. PMID: 24339143, DOI: 10.1002/jbmr.2159, ISSN: 1523-4681.

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.

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.

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.

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.

Sims NA, Johnson RW. Leukemia inhibitory factor: a paracrine mediator of bone metabolism. Growth Factors [print-electronic]. 2012 Apr; 30(2): 76-87. PMID: 22304408, DOI: 10.3109/08977194.2012.656760, ISSN: 1029-2292.

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 Res. 2011 Sep; 31(9): 2705-12. PMID: 21868511, PMCID: PMC3430074, PII: 31/9/2705, ISSN: 1791-7530.

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.

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.

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.

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.

Abbott KL, Aoki K, Lim JM, Porterfield M, Johnson R, O'Regan RM, Wells L, Tiemeyer M, Pierce M. Targeted glycoproteomic identification of biomarkers for human breast carcinoma. J. Proteome Res [print-electronic]. 2008 Apr; 7(4): 1470-80. PMID: 18271524, PMCID: PMC4932838, DOI: 10.1021/pr700792g, ISSN: 1535-3893.