Metastatic ProgressionThe focus of our lab is discovering the mechanisms controlling the initiation and progression of bone metastasis.  Using these uncovered metastatic process we hope to design novel diagnostic tests to identify patients likely to progress to metastasis and to develop treatments to prevent or slow bone metastasis.

Our prior and current work focuses primarily on prostate cancer with newer projects examining melanoma, ovarian, breast, and lung cancers. Primary  tumors use the circulation to acquire proteins and bone marrow-derived cells (BMDCs) to support tumor cell proliferation and blood vessel growth. In addition, cancer stem cells are mobilized into the circulation resulting in bone metastasis. Our goal is to understand what cells and proteins the tumor uses to signal to the bone to prepare for metastasis.

The Projects

  • SCF/CD117 Signaling as a Mechanism of Prostate Cancer Metastasis

Based upon cancer stem cell markers we previously identified in patients, we are studying the role of the tyrosine kinase receptor CD117 expression and activation on prostate cancer cell growth and mobilization. Using sorted prostate cancer cells, we are testing how CD117 expression affects primary tumor growth, premetastatic bone turnover, and cancer stem cell mobilization into the circulation. Further, we have developed SCF conditional knockout mice to examine the role of host SCF in prostate cancer metastasis.

Recent Publications:

CD117/c-kit Represents a Prostate Cancer Stem-Like Subpopulation Driving Progression, Migration and TKI Resistance

  • Developing New Spontaneous Bone Metastasis Models

In collaboration with the Orthopaedic Research Department, we are using porcine, decellularized trabecular bone to create a bone microenvironment in mice. Using syngeneic prostate cancer cells we are studying bone colonization during metastasis.

Recent Publications:

Investigating the Osteoinductive Potential of a Decellularized Xenograft Bone Substitute

  • Enumeration and Isolation of Circulating Tumor Cells using Microfluidic Chips

In collaboration with the Agah Lab at Virginia Tech, we are creating microfluidic chips to enumerate and/or capture circulating tumor cells. Initial work has focused on spiking cancer cell lines into blood to optimize devices. Ongoing work will utilize patient blood samples.

Recent Publications:

Entrapment of Prostate Cancer Circulating Tumor Cells with a Sequential Size-Based Microfluidic Chip

Comparative study of prostate cancer biophysical and migratory characteristics via iterative mechanoelectrical properties (iMEP) and standard migration assays

  • Characterizing the Bone Niche in Comorbidities and Metastasis

To understand how cancer spreads to the bone, we must first define the cells comprising the metastatic niche. Collaborating with Dr. Quillen, we are creating a methylation profiles for osteoblasts, osteoclasts, mesenchymal stem cells, osteocytes, and macrophages in the bone microenvironment across species. We will then profile changes that occur in methylation and cellular composition of the bone microenvironment in the presence of comorbidities: ovarian cancer, breast cancer and diet-induced obesity with the Cook lab, radiation or osteoarthritis with the Willey Lab.

Recent Publications:

Cartilage oligomeric matrix protein in patients with osteoarthritis is independently associated with metastatic disease in prostate cancer

  • Platelet TSP-1 and TGF-β1 in Prostate Cancer-Induced Bone Remodeling

We have demonstrated that platelets are required for tumor-induced bone remodeling in preparation for future metastasis. Using total and platelet-specific knockout mice, we are examining the role of the TSP-1/TGF-β1 signaling axis in primary tumor growth and premetastatic bone turnover.

Recent Publications:

Platelet TSP-1 Controls Prostate Cancer-Induced Osteoclast Differentiation and Bone Marrow-Derived Cell Mobilization through TGF-beta1

  • Platelet Sequestered Tumor Markers and Circulating Stem Cells in Prostate Carcinoma

In collaboration with clinicians, we are identifying possible biomarkers for advanced prostate cancers. Using patient blood samples before and after tumor resection we are measuring the levels of circulating cancer stem cells and tumor-derived proteins in circulating platelets. Markers of cancer presence will be absent in the samples after tumor resection. With this method, we can also examine markers of cancer recurrence and metastasis in patients who experience disease progression.

Recent Publications:

CD117+ cells in the circulation are predictive of advanced prostate cancer

Lab Mission Statement

Doing good, translational science with near-term patient impact while training the next generation of young scientists.

Funding for the Kerr Lab

Chronic Disease Research Fund 3/1/21-1/31/23

WFUSOM CTSI Ignition Fund 2/26/21-5/31/21

WFBCCC SBT Pilot Award 7/1/19-5/31/21

WFUSOM CTSI Pilot Award 4/1/19-9/30/20

WFUSOM CTSI Ignition Fund 1/15/19-4/10/19

Elsa U. Pardee Foundation Award 12/1/18-11/30/19

NIH/NCI Pathway to Independence Award K99/R00 CA175291 2/1/14-11/30/19

WFUSOM CTSI Ignition Fund 12/20/16-3/10/17

NIH/NCI Ruth L. Kirschstein NRSA F32 CA 142133 1/1/11-3/15/13

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