Rachelle W. Johnson, Ph.D.

Assistant Professor
Medicine, Division of Clinical Pharmacology
Member
Graduate Program in Cancer Biology
Member
Vanderbilt-Ingram Cancer Center
Medical Research Building IV
2215B Garland Avenue
Room / Suite
1165C
Nashville
Tennessee
37232
(615) 875-8965

Postdoctoral Scholar / Research Associate, Radiation Oncology, 2014-2016, Stanford University

Postdoctoral Fellow, Bone Cell Biology and Disease Unit, 2011-2013, St. Vincent's Institute

Ph.D. Cancer Biology, 2011, Vanderbilt University

B.S. Biochemistry and Molecular Biology, 2007, University of Georgia

Background

Dr. Johnson earned her doctorate in Cancer Biology from Vanderbilt University, where she studied bone metastatic breast cancer with Drs. Gregory Mundy and Julie Sterling in the Vanderbilt Center for Bone Biology. She then relocated to Melbourne, Australia to pursue a post-doc with Drs. Natalie Sims and Jack Martin in basic bone biology in order to better understand the physiological processes of skeletal homeostasis that may impact upon tumor cells. As a postdoc in Melbourne she characterized the skeletal phenotype of several glycoprotein-130 (gp130) and SOCS3 (a gp130 downstream target) bone conditional knockout mouse models and gained experience in mouse genetics, bone histomorphometry, and microCT. She then joined Dr. Amato Giaccia’s laboratory as a Postdoctoral Scholar at Stanford University, where she returned to the bone metastasis field.

Her current work is focused on the mechanisms driving tumor cell dormancy in bone and the molecular processes that enable disseminated tumor cells to colonize the bone. In particular she is interested in the role of leukemia inhibitory factor (LIF) signaling and hypoxia signaling in breast cancer dissemination and metastasis to the bone marrow.

Complete Bibliography

Research Information

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. Improvements in the clinical care of patients with primary breast cancer have 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.

My particular interest lies in the role of hypoxic (low oxygen) regulation of leukemia inhibitory factor (LIF) signaling in bone metastasis, since the bone marrow is a naturally hypoxic microenvironment, and the role of LIF and its receptor (LIFR) as a pro-dormancy signal via both autocrine and paracrine actions within the bone marrow. Projects include the identification of dormancy-associated genes across multiple models of breast cancer cells as they exit dormancy, and characterization of a novel bone metastatic breast cancer cell lines that more accurately reflect the human disease.

Techniques

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.

In vitro

  • Real-time qPCR
  • Western blotting
  • Promoter assays
  • Cytokine treatment
  • Histology/immunohistochemistry
  • Immunostaining
  • Migration/invasion assays
  • siRNA/shRNA
  • Hypoxia

In vivo

  • Xenograft (Athymic nude) and syngeneic (Balb/c) mouse models
    • Intracardiac inoculation of tumor cells
    • Mammary fat pad inoculation of tumor cells
    • Subcutaneous inoculation of tumor cells
  • Transgenic mouse models
    • PyMT spontaneous mouse mammary carcinoma model
    • MMTVCre.HIF1af/f transgenic mouse model
    • MMTVCre.HIF2af/f transgenic mouse model
    • MMTVCre.VHLf/f transgenic mouse model
  • Imaging
    • Optical imaging to detect fluorescent/luminescent tumor cells(Maestro/Pearl)
    • Radiography (Faxitron) to detect tumor-induced bone destruction
    • MicroCT (Scanco) to examine bone microarchitecture in naive and tumor-bearing long bones

In silico

  • The Cancer Genome Atlas
  • STRING