Preston Campbell, PhD

Preston Campbell, PhD

Nashville, Tennessee, United States
2K followers 500+ connections

About

A product-focused scientific leader and entrepreneur. Expertise spans pre-clinical and…

Contributions

Activity

Join now to see all activity

Experience

  • BRĒZ Graphic
  • -

    United States

  • -

    Nashville Metropolitan Area

  • -

    Nashville, TN, United States

  • -

    Greater Nashville Area, TN

  • -

  • -

    Greater Nashville Area, TN

  • -

  • -

  • -

    Greater Nashville Area, TN

  • -

    Nashville, Tennessee, United States

  • -

    Greater Nashville Area, TN

  • -

    Nashville TN

  • -

    Nashville, TN

  • -

    San Antonio, Texas Area

  • -

    Corpus Christi

Education

  • Vanderbilt University Graphic

    Vanderbilt University

    Pharmacology of chronic stress and cancer metastasis.

  • Activities and Societies: School Paper, SACNAS, Immunological Research,

Publications

  • Dual targeting c-met and VEGFR2 in osteoblasts suppresses growth and osteolysis of prostate cancer bone metastasis.

    Cancer Letters

    Prostate cancer characteristically induces osteoblastic bone metastasis, for which no therapies are available. A dual kinase inhibitor of c-Met and VEGFR-2 (cabozantinib) was shown to reduce prostate cancer growth in bone, with evidence for suppressing osteoblastic activity. However, c-Met and VEGFR2 signaling in osteoblasts in the context of bone metastasis remain unclear. Here we show using cultured osteoblasts that hepatocyte growth factor (HGF) and VEGF-A increased receptor activator of…

    Prostate cancer characteristically induces osteoblastic bone metastasis, for which no therapies are available. A dual kinase inhibitor of c-Met and VEGFR-2 (cabozantinib) was shown to reduce prostate cancer growth in bone, with evidence for suppressing osteoblastic activity. However, c-Met and VEGFR2 signaling in osteoblasts in the context of bone metastasis remain unclear. Here we show using cultured osteoblasts that hepatocyte growth factor (HGF) and VEGF-A increased receptor activator of NFκB ligand (RANKL) and M-CSF, two essential factors for osteoclastogenesis. Insulin-like growth factor-1 (IGF1) also increased RANKL and M-CSF via c-Met transactivation. The conditioned media from IGF1-, HGF-, or VEGFA-treated osteoblasts promoted osteoclastogenesis that was reversed by inhibiting c-Met and/or VEGFR2 in osteoblasts. In vivo experiments used cabozantinib-resistant prostate cancer cells (PC-3 and C4-2B) to test the effects of c-Met/VEGFR2 inhibition specifically in osteoblasts. Cabozantinib (60 mg/kg, 3 weeks) suppressed tumor growth in bone and reduced expression of RANKL and M-CSF and subsequent tumor-induced osteolysis. Collectively, inhibition of c-Met and VEGFR2 in osteoblasts reduced RANKL and M-CSF expression, and associated with reduction of tumor-induced osteolysis, suggesting that c-Met and VEGFR2 are promising therapeutic targets in bone metastasis.

    See publication
  • Skeletal Colonization by Breast Cancer Cells Is Stimulated by an Osteoblast and B2AR-dependent Neo-angiogenic Switch

    Journal of Bone and Mineral Research

    This research showed that stimulation of the β2AR in osteoblasts triggers a Vegf-dependent neo-angiogenic switch that promotes bone vascular density and the colonization of the bone microenvironment by metastatic breast cancer cells.

    Other authors
    See publication
  • Development of a RSK Inhibitor as a Novel Therapy for Triple Negative Breast Cancer

    Molecular Cancer Therapeutics

    Metastatic breast cancer is an incurable disease and identification of novel therapeutic opportunities is vital. Triple negative breast cancer (TNBC) frequently metastasizes and high levels of activated RSK, a downstream MEK-ERK1/2 effector, are found in TNBC. We demonstrate using direct pharmacological and genetic inhibition of RSK1/2 that these kinases contribute to the TNBC metastatic process in vivo. Kinase profiling demonstrated that RSK1 and RSK2 are the predominant kinases targeted by…

    Metastatic breast cancer is an incurable disease and identification of novel therapeutic opportunities is vital. Triple negative breast cancer (TNBC) frequently metastasizes and high levels of activated RSK, a downstream MEK-ERK1/2 effector, are found in TNBC. We demonstrate using direct pharmacological and genetic inhibition of RSK1/2 that these kinases contribute to the TNBC metastatic process in vivo. Kinase profiling demonstrated that RSK1 and RSK2 are the predominant kinases targeted by the new inhibitor, which is based on the natural product, SL0101. Further evidence for selectivity was provided by the observations that silencing RSK1 and RSK2 eliminated the ability of the analogue to further inhibit survival or proliferation of a TNBC cell line. In vivo, the new derivative was as effective as the FDA-approved MEK inhibitor, trametinib, in reducing the establishment of metastatic foci. Importantly, inhibition of RSK1/2 did not result in activation of AKT, which is known to limit the efficacy of MEK inhibitors in the clinic. Our results demonstrate that RSK is a major contributor to the TNBC metastatic program and provide preclinical proof-of-concept for the efficacy of the novel SL0101 analogue in vivo.

    Other authors
    See publication
  • TRIzol and Alu qPCR-based quantification of metastatic seeding within the skeleton

    Nature Scientific Reports

    Current methods for detecting disseminated tumor cells in the skeleton are limited by expense and technical complexity. We describe a simple and inexpensive method to quantify, with single cell sensitivity, human metastatic cancer in the mouse skeleton, concurrently with host gene expression, using TRIzol-based DNA/RNA extraction and Alu sequence qPCR amplification. This approach enables precise quantification of tumor cells and corresponding host gene expression during metastatic colonization…

    Current methods for detecting disseminated tumor cells in the skeleton are limited by expense and technical complexity. We describe a simple and inexpensive method to quantify, with single cell sensitivity, human metastatic cancer in the mouse skeleton, concurrently with host gene expression, using TRIzol-based DNA/RNA extraction and Alu sequence qPCR amplification. This approach enables precise quantification of tumor cells and corresponding host gene expression during metastatic colonization in xenograft models.

    Other authors
    See publication
  • Targeting c-Met and VEGFR2 in the stromal compartment of prostate cancer bone metastasis

    Cancer Research

    c-Met and VEGFR2 are promising therapeutic targets in the stromal compartment of prostate cancer bone metastasis, suggesting hat the effects of cabozantinib on skeletal-related events of prostate cancer are, at least in part, mediated by suppression of osteoblast function.

    Other authors
    See publication
  • A Secreted Bacterial Protease Tailors the Staphylococcus aureus Virulence Repertoire to Modulate Bone Remodeling during Osteomyelitis

    Cell Host and Microbe

    Osteomyelitis is a common manifestation of invasive Staphylococcus aureus infection. Pathogen-induced bone destruction limits antimicrobial penetration to the infectious focus and compromises treatment of osteomyelitis. To investigate mechanisms of S. aureus-induced bone destruction, we developed a murine model of osteomyelitis. Microcomputed tomography of infected femurs revealed that S. aureus triggers profound alterations in bone turnover. The bacterial regulatory locus sae was found to be…

    Osteomyelitis is a common manifestation of invasive Staphylococcus aureus infection. Pathogen-induced bone destruction limits antimicrobial penetration to the infectious focus and compromises treatment of osteomyelitis. To investigate mechanisms of S. aureus-induced bone destruction, we developed a murine model of osteomyelitis. Microcomputed tomography of infected femurs revealed that S. aureus triggers profound alterations in bone turnover. The bacterial regulatory locus sae was found to be critical for osteomyelitis pathogenesis, as Sae-regulated factors promote pathologic bone remodeling and intraosseous bacterial survival. Exoproteome analyses revealed the Sae-regulated protease aureolysin as a major determinant of the S. aureus secretome and identified the phenol-soluble modulins as aureolysin-degraded, osteolytic peptides that trigger osteoblast cell death and bone destruction. These studies establish a murine model for pathogen-induced bone remodeling, define Sae as critical for osteomyelitis pathogenesis, and identify protease-dependent exoproteome remodeling as a major determinant of the staphylococcal virulence repertoire.

    Other authors
    • Jim Cassatt
    • ND Hammer
    • MA Benson
    • Dan Perrein
    • LN Mrak
    • MS Smeltzer
    • VJ Torres
    • EP Skaar
    See publication
  • Control of Bone Remodeling by the Peripheral Sympathetic Nervous System

    Calcified Tissue International

    The skeleton is no longer seen as a static, isolated, and mostly structural organ. Over the last two decades, a more complete picture of the multiple functions of the skeleton has emerged, and its interactions with a growing number of apparently unrelated organs have become evident. The skeleton not only reacts to mechanical loading and inflammatory, hormonal, and mineral challenges, but also acts of its own accord by secreting factors controlling the function of other tissues, including the…

    The skeleton is no longer seen as a static, isolated, and mostly structural organ. Over the last two decades, a more complete picture of the multiple functions of the skeleton has emerged, and its interactions with a growing number of apparently unrelated organs have become evident. The skeleton not only reacts to mechanical loading and inflammatory, hormonal, and mineral challenges, but also acts of its own accord by secreting factors controlling the function of other tissues, including the kidney and possibly the pancreas and gonads. It is thus becoming widely recognized that it is by nature an endocrine organ, in addition to a structural organ and site of mineral storage and hematopoiesis. Consequently and by definition, bone homeostasis must be tightly regulated and integrated with the biology of other organs to maintain whole body homeostasis, and data uncovering the involvement of the central nervous system (CNS) in the control of bone remodeling support this concept. The sympathetic nervous system (SNS) represents one of the main links between the CNS and the skeleton, based on a number of anatomic, pharmacologic, and genetic studies focused on β-adrenergic receptor (βAR) signaling in bone cells. The goal of this report was to review the data supporting the role of the SNS and βAR signaling in the regulation of skeletal homeostasis.

    Other authors
    See publication
  • Models of Bone Metastasis

    J Vis Exp. 2012 Sep 4;(67):e4260. doi: 10.3791/4260.

    This manuscript details inoculation procedures and highlights key steps in post inoculation analyses. Specifically, it includes cell culture, tumor cell inoculation procedures for intracardiac and intratibial inoculations, as well as brief information regarding weekly monitoring by x-ray, fluorescence and histomorphometric analyses.

    Other authors
    See publication
  • Autonomic Innervation of the Skeleton

    Primer on the Autonomic Nervous System

    Review of bone innervation and function.

    Other authors
    See publication

Patents

  • Aromatherapy compositions for improving cognitive function

    Issued FR WO2020102334A9

  • Handheld vaporizing device assembly

    Issued US USD869085S1

Courses

  • Drug and Device Development

    -

  • Fundamentals of Management

    MGRL 194

  • Network Analysis in Systems Biology

    -

  • Pharmacokinetics

    -

  • Summer Intensive for Tech Entrepreneurship and Commercialization

    -

Honors & Awards

  • Keynote Speaker

    Cancer Survivor Network Annual Retreat

    "Complex Systems and Cancer"

  • Precision Medicine Travel Award

    CWRU Institute for Computational Biology

  • Keystone Symposia Fellow 2016-17

    Keystone Symposia

  • 2nd place Duke/UNC Case Competition

    Duke APD Consulting Club

    2nd Place (of 16 final competitors) in a team -based drug development strategy competition. Team mates were Sean Bedingfield and Sue Hyun Lee

  • NCI Postdoctoral Fellowship (Grant)

    National Cancer Institute

  • FLARES Fellow (Future Leaders Advancing Research in Endocrinology)

    Endocrine Society

  • Top Peer Reviewed Abstract

    11th Annual Host-Tumor Interactions Program

    High scoring abstract and presentation for cancer biology

  • Plenary Presentation and Lecture

    International Bone and Mineral Society

  • Young Investigator Award

    ASBMR American Society for Bone and Mineral Research

  • Young Investigator Award

    Cancer and Bone Society

  • SACNAS Research Grant

    Society for the Advancement of Chicanos and Native Americans in Science

    Undergraduate research grant investigating mechanisms in bacterial meningitis under the mentorship of Lilian Waldbeser

Languages

  • English

    Native or bilingual proficiency

  • Spanish

    Limited working proficiency

Organizations

  • American Association of Pharmaceutical Sciences

    -

    - Present
  • Endocrine Society

    Member

    - Present
  • Metastasis Research Society

    Member/Author

    -
  • Association for Chemoreception Sciences

    -

    -
  • VUADCC Vanderbilt Advanced Degree Consulting Club

    Board Member

    -
  • International Bone and Mineral Society

    Member

    -
  • CABS (CIBD) Cancer and Bone Society

    Member

    -
  • SACNAS

    Member

    -

Recommendations received

More activity by Preston

View Preston’s full profile

  • See who you know in common
  • Get introduced
  • Contact Preston directly
Join to view full profile

Other similar profiles

Explore collaborative articles

We’re unlocking community knowledge in a new way. Experts add insights directly into each article, started with the help of AI.

Explore More

Add new skills with these courses