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Paul M. Campbell, PhD
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- About
- Education and Training
- Research Profile
- Lab Staff
- Publications
- Open Positions
About
Assistant Professor
The Marvin and Concetta Greenberg Pancreatic Cancer Institute
Research Program
Lab Overview
As a member of the Marvin & Concetta Greenberg Pancreatic Cancer Institute, our lab focuses on the K-Ras oncogene and its signaling in pancreatic ductal adenocarcinoma (PDAC). While K-Ras is commonly hyperactivated (by mutation or extrinsic upstream signaling) in many cancer subtypes, and activating mutations occur in approximately 95% of PDAC cases, it remains a largely intractable target pharmacologically-speaking. Although novel mutation-specific K-Ras inhibitors are currently in clinical trials, their K-Ras G12C target is infrequent (~2%) in PDAC. As such, we are investigating the signaling cascades driven by K-Ras function to illuminate potential therapeutic targets.
Education and Training
Educational Background
- Postdoctoral Fellow, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center
- PhD, McGill University, Pharmacology & Therapeutics
- MSc, University of Toronto, Physiology
- BSc, University of Toronto, Pharmacology & Toxicology
Memberships
- American Association for Cancer Research
- American Society for Cell Biology
- American Society for Pharmacology and Experimental Therapeutics
Honors & Awards
- AACR Minority Scholar in Cancer Research Award
- Susan G. Komen Breast Cancer Foundation Postdoctoral Fellowship
- University of North Carolina Lineberger Comprehensive Cancer Center Clinical Translational Research Award
- McGill University Centre for Translational Research in Cancer Fellowship
- McGill University Faculty of Medicine Fellowship – Alex Dworkin Scholarship in Oncology
Research Profile
Research Program
Research Facility
Research Interests
Our research revolves around understanding how the Ras family of small GTPases impinges upon tumor invasion and metastasis, specifically in pancreatic ductal cancer. Ras is a nodal point of signaling, with input and activation from a wide range of stimuli including receptor tyrosine kinases, G protein-coupled receptors, integrins and extracellular matrix interactions, and chemokines. Once activated, Ras in turn triggers several signaling cascades that lead to a variety of transformed phenotypes including loss of cell cycle control, decreased cell death, and metastatic spread. Of particular interest to my lab is delineating how Ras activation in epithelial tumor cells drives signaling crosstalk to other compartments of the tumor microenvironment including stromal fibroblasts, macrophages, and vascular components. Paracrine signaling among these disparate cell populations likely contributes to protection of epithelial cells from cell cycle arrest, apoptosis, and senescence, as well as facilitating dedifferentiation and EMT.
At the same time that crosstalk affects the epithelial cells, there is evidence that aberrant activation of Ras leads to changes in extracellular matrix (ECM). Reorganization and dissolution of ECM by proteases and other enzymes accelerates cell migration for locoregional invasion and distal metastasis. In addition to Ras effects on the ECM architecture, we have recently shown that activation of this family of GTPases in pancreatic cancer leads to expression and secretion of CXC chemokines that is in part MAP kinase dependent. Vascular endothelial cells are sensitive to these chemokines via CXCR2 receptors, and respond by showing increased migration, invasion, and organization into vessel precursors. This angiogenesis may provide not only a means to nourish nascent tumors, but also serve as a conduit for malignant spread. As a result, we are interested in testing the hypothesis that small molecule inhibitors of the CXC-CXCR signaling axis may reduce the invasion and metastasis of pancreatic cancer and/or the expansion of already disseminated micrometastases.
Pancreatic cancer is also characterized by having an extensive stromal component. It is hypothesized that this bulk of fibroid tissue may be one of the reasons pancreatic cancer remains particularly insensitive to chemotherapeutic agents. Another arm of our research attempts to investigate whether tumor fibroblasts, like vascular endothelial cells, are responsive to CXC-CXCR crosstalk signaling triggered initially by epithelial K-Ras activation.
It is well established that mutational activation of K-Ras occurs very early in pancreatic ductal dysplasia and remains an important signaling impetus through the development of malignancy. We are investigating whether the signaling crosstalk between Ras and CXC chemokines is similarly triggered early in cancer progression by screening patient samples of initial dysplasia (pancreatic intraepithelial neoplasia, PanIN) to frank adenocarcinoma. By understanding the progression this signaling, we hope to uncover biomarkers to be used for screening and earlier detection.
Lab Description
Our research revolves around understanding how the Ras family of small GTPases impinges upon tumor invasion and metastasis, specifically in pancreatic ductal cancer. Ras is a nodal point of signaling, with input and activation from a wide range of stimuli including receptor tyrosine kinases, G protein-coupled receptors, integrins and extracellular matrix interactions, and chemokines. Once activated, Ras in turn triggers several signaling cascades that lead to a variety of transformed phenotypes including loss of cell cycle control, decreased cell death, and metastatic spread. Of particular interest to my lab is delineating how Ras activation in epithelial tumor cells drives signaling crosstalk to other compartments of the tumor microenvironment including stromal fibroblasts, macrophages, and vascular components. Paracrine signaling among these disparate cell populations likely contributes to protection of epithelial cells from cell cycle arrest, apoptosis, and senescence, as well as facilitating dedifferentiation and a hallmark of tumor progression and metastasis, epithelial-mesenchymal transition (EMT).
At the same time that crosstalk affects the epithelial cells, there is evidence that aberrant activation of Ras leads to changes in extracellular matrix (ECM). Reorganization and dissolution of ECM by proteases and other enzymes accelerates cell migration for locoregional invasion and distal metastasis. In addition to Ras effects on the ECM architecture, we have recently shown that activation of this family of GTPases in pancreatic cancer leads to expression and secretion of CXC chemokines that is in part MAP kinase-dependent. Vascular endothelial cells are sensitive to these chemokines via CXCR2 receptors, and respond by showing increased migration, invasion, and organization into vessel precursors. This angiogenesis may provide not only a means to nourish nascent tumors, but also serve as a conduit for malignant spread. As a result, we are interested in testing the hypothesis that small molecule inhibitors of the CXC-CXCR signaling axis may reduce the invasion and metastasis of pancreatic cancer and/or the expansion of already disseminated micrometastases.
Pancreatic cancer is also characterized by having an extensive stromal component. It is hypothesized that this bulk of fibroid tissue may be one of the reasons pancreatic cancer remains particularly insensitive to chemotherapeutic agents. Another arm of our research attempts to investigate whether tumor fibroblasts, like vascular endothelial cells, are responsive to CXC-CXCR crosstalk signaling triggered initially by epithelial K-Ras activation. It is well established that mutational activation of K-Ras occurs very early in pancreatic ductal dysplasia and remains an important signaling impetus through the development of malignancy. We are investigating whether the signaling crosstalk between Ras and CXC chemokines is similarly triggered early in cancer progression by screening patient samples of initial dysplasia (pancreatic intraepithelial neoplasia, PanIN) to frank adenocarcinoma. By understanding the progression this signaling, we hope to uncover biomarkers to be used for screening and earlier detection.
Finally, some of our recent work has demonstrated an interaction between K-Ras and the RNA-binding protein, HuR. Current investigations are looking at how K-Ras activation via genetic mutation influences HuR function and regulation of the cancer progression transcriptome, and in turn, how HuR governs K-Ras-dependent signaling in tumor epithelial cells.
Lab Staff
Ryan O'Rourke
Undergraduate Student, Franklin & Marshall College, 2021 Jeanne E. and Robert F. Ozols Undergraduate Summer Research Fellow
Room: W463
215-728-2219
Additional Staff
Laboratory Alumni/ae
Edgar Asiimwe, research intern, Duke University
Bennette Attipoe M.S. grad student
Shilpa Narayan M.S. grad student
Bailee Sliker, Ph.D., postdoctoral fellow
Matthew Stout Ph.D. grad student
Taylor Wernert, M.D. student
Undergraduate Research Students
Neha Akella, Drexel University
Julia Bacon-Henderson, Chestnut Hill College
Divya Balchander, Drexel University
James Birkenstamm, Rider University
Danielle Cole, Drexel University
Anisha Gopu, Drexel University
Maria Gurski, Catawba College
Su Yeon (Clara) Kim, Drexel University
Priya Krishnaprasad, Drexel University
Sofia Neaher, Williams College, Jeanne E. & Robert F. Ozols Undergraduate Research Fellow
Ryan O’Rourke, Franklin & Marshall College, Jeanne E. & Robert F. Ozols Undergraduate Research Fellow
Ronil Patel, Drexel University
Emily Pillet, Drexel University
Margo Randelman, Ursinus College
Sitara Soundararajan, Drexel University
Yash Varma, Drexel University
Publications
Selected Publications
S.C. Ozcan, A. Mutlu, T.H. Altunok, Y. Gurpinar, A. Sarioglu, S. Guler, R.J. Muchut, A.A. Iglesias, S. Celikler, P.M. Campbell, and A. Yalcin. 2021. Simultaneous Inhibition of PFKFB3 and GLS1 Selectively Kills KRAS-transformed Pancreatic Cells. Biochem Biophys Res Commun, 571:118-124. Pubmed.
B.H. Sliker and P.M. Campbell. 2021. Fibroblasts Influence the Efficacy, Resistance, and Future Use of Vaccines and Immunotherapy in Cancer Treatment. Vaccines, 9:634-653. Pubmed
A. Thadi, W.F. Morano, M. Khalili, B.B. Babcock, M.F. Shaikh, D.S. Foster, Y. Piazza, E.M. Gleeson, E. Goldstein, L. Steele, P.M. Campbell, B. Lin, M.R. Pincus, W.B. Bowne. 2021. Molecular targeting of H/MDM-2 oncoprotein in human colon cancer cells and stem-like colonic epithelial derived progenitor cells. Anticancer Res, 41:27-42. Pubmed.
Sliker B.H. and Campbell P.M. 2020. Ras and Ras Signaling as a therapeutic target in cancer. In Comprehensive Pharmacology, Terry Kenakin, Ph.D., editor, in press.
A. Thadi, E.M. Gleeson, M. Khalili, M.F. Shaikh, E. Goldstein, W.F. Morano, L.M. Daniels, N. Grandhi, H. Glatthorn, S.D. Richard, P.M. Campbell, M.R. Pincus, W.B. Bowne. 2020. Anti-cancer tumor cell necrosis of multidrug resistant ovarian cancer cell lines depends on high expression of HDM-2 protein in their membranes. Ann Clin Lab Sci, 50:611-624. Pubmed
A. Thadi, L. Lewis, E. Goldstein, A. Aggarwal, M. Khalili, L. Steele, B. Polyak, S. Seydafkan, M.H. Bluth, K.A. Ward, M. Styler, P.M. Campbell, M.R. Pincus, W.B. Bowne. 2020. Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells but Not Normal Hematopoietic Cells. Anticancer Res, 40:4857-4867. Pubmed
M.C. Stout and P.M. Campbell. 2018. RASpecting the oncogene: New pathways to therapeutic advances. Biochem Pharm, 158: 217-228. Pubmed
M.C. Stout, S. Narayan, E.S. Pillet, J.S. Salvino, P.M. Campbell. 2018. Inhibition of CX3CR1 Reduces Cell Motility and Viability in Pancreatic Adenocarcinoma Epithelial Cells. Biochem Biophys Res Commun, 495:2264– 2269. PubMed
S. Lal*, E. Cheung*, M. Zarei*, R. Preet, S.N. Chand, N.C. Mambelli-Lisboa, C. Romeo, M.C. Stout, E. Londin, A. Goetz, C. Yabar, A. Nevler, C.J. Yeo, P.M. Campbell, J.M. Winter, D.A. Dixon, J.R. Brody. 2017. CRISPR knockout of the HuR gene in pancreatic and colorectal cancer cells causes a xenograft lethal phenotype. * Contributed equally. Mol Cancer Res, 15:696-707. PubMed
M.C. Stout, E. Asiimwe, J.R. Birkenstamm, S.Y. Kim, P.M. Campbell. 2014. Analyzing Ras-associated Cell Proliferation Signaling. Methods Mol Biol, 1170:393-409. PubMed
P.M. Campbell. 2014. Oncogenic Ras pushes (and pulls) cell cycle progression through ERK activation. Methods Mol Biol, 1170:155-163. PubMed
H.R. Siddique, D.J. Liao, S.K. Mishra, T. Schuster, L. Wang, B. Matter, P.M. Campbell, P. Villalta, S. Nanda, Y. Deng, M. Saleem. 2012. Epicatechin-rich cocoa polyphenol inhibits Kras-activated pancreatic ductal carcinoma cell growth in vitro and in a mouse model. Int J Cancer, 131:1720–1731. PubMed
P.M. Campbell*, N. Boufaied*, J.J. Fiordalisi, A.D. Cox, P. Falardeau, C.J. Der, H. Gourdeau. 2010. TLN-4601 suppresses growth and induces apoptosis of pancreatic carcinoma cells through inhibition of Ras-MAPK signaling. J Mol Signal, 5:18. * Contributed equally PubMed
Y. Matsuo*, P.M. Campbell*, R.A. Brekken, B. Sung, M.M. Ouellette, J.B. Fleming, B.B. Aggarwal, C.J. Der, S. Guha. 2009. K-Ras promotes angiogenesis mediated by immortalized human pancreatic epithelial cells through MAP kinase signaling pathways. Mol Cancer Res, 7:799-808. * Contributed equally. PubMed
P.M. Campbell, K.M. Lee, M.M. Ouellette, H.J. Kim, A.L. Groehler, V. Khazak, C.J. Der. 2008. Ras-driven transformation of human nestin-positive pancreatic epithelial cells. Methods Enzymol 439:451-65. PubMed
P.M. Campbell, A.L. Groehler, K.M. Lee, M.M. Ouellette, V. Khazak, C.J. Der. 2007. K-Ras promotes growth transformation and invasion of immortalized human pancreatic cells by Raf and phosphatidylinositol 3-kinase signaling. Cancer Res 67:2098-2106. PubMed
Open Positions
Open Positions
Postdoctoral Fellow
About the Position
The main goals of the Campbell lab are to understand how signaling within the tumor microenvironment drives incidence and progression of gastrointestinal cancers, predominantly pancreatic cancer. We employ basic and translational science approaches that ultimately lead to improved therapeutics. The lab is part of the highly collaborative Marvin and Concetta Greenberg Pancreatic Cancer Institute and the associated Pancreatic Cancer Translational Working Group.
The ideal candidate will be engaged in identifying novel mechanisms that promote the development of pancreatic cancer from early lesions through to metastatic disease, using fundamental mechanisms discovered in model organisms and patient samples as starting points for deeper discovery. Familiarity with methods of manipulating gene expression and signaling in mammalian cultured cells and mouse models, as well as experience in molecular biology are desired.
Applicants should have PhD in biomedical sciences or related field. This position requires considerable experience in cell and molecular biology techniques, with a strong bias towards candidates with significant cancer research experience. Excellent written and oral communication skills are required. Recent or soon-to-be graduates are preferred.
About the Training Environment
As one of the four original cancer centers to receive comprehensive designation from the National Cancer Institute, Fox Chase Cancer Center has been at the forefront of cancer research for almost 90 years. We are home to excellent research facilities, top clinicians and scientists, and outstanding patient care. Our singular focus on cancer, which couples discovery science with state of the art clinical care and population health, remains the foundation of our work.
The scientist training programs at Fox Chase Cancer Center provide professional development opportunities in four core areas identified as crucial for successful careers in science, research, and health care including communication, leadership, teaching, and mentorship. Upon joining the program, graduate students and postdocs develop individual development plans to help guide their growth. Training throughout the year is supplemented with free professional development opportunities, including a robust ‘How To’ series, writing courses, networking, mentorship, and teaching opportunities, a trainee-led seminar series, a trainee-led annual Research Conference, and more. Postdocs at Fox Chase Cancer Center are supported by the Temple University Postdoc Association and the Office of Academic Affairs at Fox Chase, and are compensated with competitive pay and benefits.
In addition to the robust training program, scientists at Fox Chase Cancer Center benefit from being part of the rich scientific and biotech environment in the Philadelphia region. Many of our former trainees are now employees (and contacts) at nearby institutions and companies, including The Wistar Institute, Merck, GSK, AACR, and numerous others.
To Apply
Interested candidates should send a cover letter describing their previous research experience and future plans, a current CV, and a list of three references to: Dr. Paul Campbell at campbell_labpostdoc@temple.edu.
Research Technician
About the Position
A full time research technician position is available in a cancer biology laboratory in the Cancer Signaling & Epigenetics Program and the Marvin & Concetta Greenberg Pancreatic Cancer Institute at Fox Chase Cancer Center in Philadelphia. The main interests of the Campbell lab are to understand how signaling from the tumor microenvironment drives incidence and progression of gastrointestinal cancers, predominantly pancreatic cancer.
The successful candidate will conduct, under supervision of the principal investigator, experiments in signaling biology, biochemistry, and molecular pharmacology aimed at understanding the molecular mechanisms of action of cancer invasion with a goal of discovering and validating new therapeutic targets and biomarkers.
In addition, the successful candidate will be responsible for ordering and organizing laboratory supplies, maintaining equipment, cataloging reagents, and other organizational tasks.
It is expected that the individual will present his/her research findings internally and for the motivated candidate, at local and national conferences.
Applicant should have a bachelor’s degree in a basic medical science discipline (physiology, biochemistry, molecular biology etc.) or biology and experience working in a research laboratory is required. Experience in mammalian cell culture, basic molecular biology techniques (transformation, gene subcloning, DNA mini- and maxi-preps, PCR), and basic biochemistry techniques (SDS-PAGE, western blots, immunoprecipitation, immunohistochemistry) is strongly preferred.
Excellent communication skills (verbal and written) and interpersonal skills are required. The successful candidate will be a liaison amongst multiple labs and clinical personnel within our Cancer Center, with collaborators at other research institutes, and with supply vendors.
Excellent organizational skills required: ability to multitask will be essential for success in this position.
About the Training Environment
As one of the four original cancer centers to receive comprehensive designation from the National Cancer Institute, Fox Chase Cancer Center has been at the forefront of cancer research for almost 90 years. We are home to excellent research facilities, top clinicians and scientists, and outstanding patient care. Our singular focus on cancer, which couples discovery science with state of the art clinical care and population health, remains the foundation of our work.
The scientist training programs at Fox Chase Cancer Center provide professional development opportunities in four core areas identified as crucial for successful careers in science, research, and health care including communication, leadership, teaching, and mentorship. Upon joining the program, graduate students and postdocs develop individual development plans to help guide their growth. Training throughout the year is supplemented with free professional development opportunities, including a robust ‘How To’ series, writing courses, networking, mentorship, and teaching opportunities, a trainee-led seminar series, a trainee-led annual Research Conference, and more. Postdocs at Fox Chase Cancer Center are supported by the Temple University Postdoc Association and the Office of Academic Affairs at Fox Chase, and are compensated with competitive pay and benefits.
In addition to the robust training program, scientists at Fox Chase Cancer Center benefit from being part of the rich scientific and biotech environment in the Philadelphia region. Many of our former trainees are now employees (and contacts) at nearby institutions and companies, including The Wistar Institute, Merck, GSK, AACR, and numerous others.
To Apply
Interested candidates should send a cover letter describing their previous research experience, a current resume, and a list of three references to: Dr. Paul Campbell at campbell_labtech@temple.edu.
Contact Information
Paul.Campbell@fccc.edu
Office Phone: 215-728-2211
Office: W463
Contact Information
Paul.Campbell@fccc.edu
Office Phone: 215-728-2211
Office: W463
Assistant Professor
The Marvin and Concetta Greenberg Pancreatic Cancer Institute
Research Program
Lab Overview
As a member of the Marvin & Concetta Greenberg Pancreatic Cancer Institute, our lab focuses on the K-Ras oncogene and its signaling in pancreatic ductal adenocarcinoma (PDAC). While K-Ras is commonly hyperactivated (by mutation or extrinsic upstream signaling) in many cancer subtypes, and activating mutations occur in approximately 95% of PDAC cases, it remains a largely intractable target pharmacologically-speaking. Although novel mutation-specific K-Ras inhibitors are currently in clinical trials, their K-Ras G12C target is infrequent (~2%) in PDAC. As such, we are investigating the signaling cascades driven by K-Ras function to illuminate potential therapeutic targets.
Education
Educational Background
- Postdoctoral Fellow, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center
- PhD, McGill University, Pharmacology & Therapeutics
- MSc, University of Toronto, Physiology
- BSc, University of Toronto, Pharmacology & Toxicology
Memberships
- American Association for Cancer Research
- American Society for Cell Biology
- American Society for Pharmacology and Experimental Therapeutics
Honors & Awards
- AACR Minority Scholar in Cancer Research Award
- Susan G. Komen Breast Cancer Foundation Postdoctoral Fellowship
- University of North Carolina Lineberger Comprehensive Cancer Center Clinical Translational Research Award
- McGill University Centre for Translational Research in Cancer Fellowship
- McGill University Faculty of Medicine Fellowship – Alex Dworkin Scholarship in Oncology
Research Profile
Research Facility
Research Interests
Our research revolves around understanding how the Ras family of small GTPases impinges upon tumor invasion and metastasis, specifically in pancreatic ductal cancer. Ras is a nodal point of signaling, with input and activation from a wide range of stimuli including receptor tyrosine kinases, G protein-coupled receptors, integrins and extracellular matrix interactions, and chemokines. Once activated, Ras in turn triggers several signaling cascades that lead to a variety of transformed phenotypes including loss of cell cycle control, decreased cell death, and metastatic spread. Of particular interest to my lab is delineating how Ras activation in epithelial tumor cells drives signaling crosstalk to other compartments of the tumor microenvironment including stromal fibroblasts, macrophages, and vascular components. Paracrine signaling among these disparate cell populations likely contributes to protection of epithelial cells from cell cycle arrest, apoptosis, and senescence, as well as facilitating dedifferentiation and EMT.
At the same time that crosstalk affects the epithelial cells, there is evidence that aberrant activation of Ras leads to changes in extracellular matrix (ECM). Reorganization and dissolution of ECM by proteases and other enzymes accelerates cell migration for locoregional invasion and distal metastasis. In addition to Ras effects on the ECM architecture, we have recently shown that activation of this family of GTPases in pancreatic cancer leads to expression and secretion of CXC chemokines that is in part MAP kinase dependent. Vascular endothelial cells are sensitive to these chemokines via CXCR2 receptors, and respond by showing increased migration, invasion, and organization into vessel precursors. This angiogenesis may provide not only a means to nourish nascent tumors, but also serve as a conduit for malignant spread. As a result, we are interested in testing the hypothesis that small molecule inhibitors of the CXC-CXCR signaling axis may reduce the invasion and metastasis of pancreatic cancer and/or the expansion of already disseminated micrometastases.
Pancreatic cancer is also characterized by having an extensive stromal component. It is hypothesized that this bulk of fibroid tissue may be one of the reasons pancreatic cancer remains particularly insensitive to chemotherapeutic agents. Another arm of our research attempts to investigate whether tumor fibroblasts, like vascular endothelial cells, are responsive to CXC-CXCR crosstalk signaling triggered initially by epithelial K-Ras activation.
It is well established that mutational activation of K-Ras occurs very early in pancreatic ductal dysplasia and remains an important signaling impetus through the development of malignancy. We are investigating whether the signaling crosstalk between Ras and CXC chemokines is similarly triggered early in cancer progression by screening patient samples of initial dysplasia (pancreatic intraepithelial neoplasia, PanIN) to frank adenocarcinoma. By understanding the progression this signaling, we hope to uncover biomarkers to be used for screening and earlier detection.
Lab Description
Our research revolves around understanding how the Ras family of small GTPases impinges upon tumor invasion and metastasis, specifically in pancreatic ductal cancer. Ras is a nodal point of signaling, with input and activation from a wide range of stimuli including receptor tyrosine kinases, G protein-coupled receptors, integrins and extracellular matrix interactions, and chemokines. Once activated, Ras in turn triggers several signaling cascades that lead to a variety of transformed phenotypes including loss of cell cycle control, decreased cell death, and metastatic spread. Of particular interest to my lab is delineating how Ras activation in epithelial tumor cells drives signaling crosstalk to other compartments of the tumor microenvironment including stromal fibroblasts, macrophages, and vascular components. Paracrine signaling among these disparate cell populations likely contributes to protection of epithelial cells from cell cycle arrest, apoptosis, and senescence, as well as facilitating dedifferentiation and a hallmark of tumor progression and metastasis, epithelial-mesenchymal transition (EMT).
At the same time that crosstalk affects the epithelial cells, there is evidence that aberrant activation of Ras leads to changes in extracellular matrix (ECM). Reorganization and dissolution of ECM by proteases and other enzymes accelerates cell migration for locoregional invasion and distal metastasis. In addition to Ras effects on the ECM architecture, we have recently shown that activation of this family of GTPases in pancreatic cancer leads to expression and secretion of CXC chemokines that is in part MAP kinase-dependent. Vascular endothelial cells are sensitive to these chemokines via CXCR2 receptors, and respond by showing increased migration, invasion, and organization into vessel precursors. This angiogenesis may provide not only a means to nourish nascent tumors, but also serve as a conduit for malignant spread. As a result, we are interested in testing the hypothesis that small molecule inhibitors of the CXC-CXCR signaling axis may reduce the invasion and metastasis of pancreatic cancer and/or the expansion of already disseminated micrometastases.
Pancreatic cancer is also characterized by having an extensive stromal component. It is hypothesized that this bulk of fibroid tissue may be one of the reasons pancreatic cancer remains particularly insensitive to chemotherapeutic agents. Another arm of our research attempts to investigate whether tumor fibroblasts, like vascular endothelial cells, are responsive to CXC-CXCR crosstalk signaling triggered initially by epithelial K-Ras activation. It is well established that mutational activation of K-Ras occurs very early in pancreatic ductal dysplasia and remains an important signaling impetus through the development of malignancy. We are investigating whether the signaling crosstalk between Ras and CXC chemokines is similarly triggered early in cancer progression by screening patient samples of initial dysplasia (pancreatic intraepithelial neoplasia, PanIN) to frank adenocarcinoma. By understanding the progression this signaling, we hope to uncover biomarkers to be used for screening and earlier detection.
Finally, some of our recent work has demonstrated an interaction between K-Ras and the RNA-binding protein, HuR. Current investigations are looking at how K-Ras activation via genetic mutation influences HuR function and regulation of the cancer progression transcriptome, and in turn, how HuR governs K-Ras-dependent signaling in tumor epithelial cells.
Lab Staff
Ryan O'Rourke
Undergraduate Student, Franklin & Marshall College, 2021 Jeanne E. and Robert F. Ozols Undergraduate Summer Research Fellow
Room: W463
215-728-2219
Additional Staff
Laboratory Alumni/ae
Edgar Asiimwe, research intern, Duke University
Bennette Attipoe M.S. grad student
Shilpa Narayan M.S. grad student
Bailee Sliker, Ph.D., postdoctoral fellow
Matthew Stout Ph.D. grad student
Taylor Wernert, M.D. student
Undergraduate Research Students
Neha Akella, Drexel University
Julia Bacon-Henderson, Chestnut Hill College
Divya Balchander, Drexel University
James Birkenstamm, Rider University
Danielle Cole, Drexel University
Anisha Gopu, Drexel University
Maria Gurski, Catawba College
Su Yeon (Clara) Kim, Drexel University
Priya Krishnaprasad, Drexel University
Sofia Neaher, Williams College, Jeanne E. & Robert F. Ozols Undergraduate Research Fellow
Ryan O’Rourke, Franklin & Marshall College, Jeanne E. & Robert F. Ozols Undergraduate Research Fellow
Ronil Patel, Drexel University
Emily Pillet, Drexel University
Margo Randelman, Ursinus College
Sitara Soundararajan, Drexel University
Yash Varma, Drexel University
Publications
Selected Publications
S.C. Ozcan, A. Mutlu, T.H. Altunok, Y. Gurpinar, A. Sarioglu, S. Guler, R.J. Muchut, A.A. Iglesias, S. Celikler, P.M. Campbell, and A. Yalcin. 2021. Simultaneous Inhibition of PFKFB3 and GLS1 Selectively Kills KRAS-transformed Pancreatic Cells. Biochem Biophys Res Commun, 571:118-124. Pubmed.
B.H. Sliker and P.M. Campbell. 2021. Fibroblasts Influence the Efficacy, Resistance, and Future Use of Vaccines and Immunotherapy in Cancer Treatment. Vaccines, 9:634-653. Pubmed
A. Thadi, W.F. Morano, M. Khalili, B.B. Babcock, M.F. Shaikh, D.S. Foster, Y. Piazza, E.M. Gleeson, E. Goldstein, L. Steele, P.M. Campbell, B. Lin, M.R. Pincus, W.B. Bowne. 2021. Molecular targeting of H/MDM-2 oncoprotein in human colon cancer cells and stem-like colonic epithelial derived progenitor cells. Anticancer Res, 41:27-42. Pubmed.
Sliker B.H. and Campbell P.M. 2020. Ras and Ras Signaling as a therapeutic target in cancer. In Comprehensive Pharmacology, Terry Kenakin, Ph.D., editor, in press.
A. Thadi, E.M. Gleeson, M. Khalili, M.F. Shaikh, E. Goldstein, W.F. Morano, L.M. Daniels, N. Grandhi, H. Glatthorn, S.D. Richard, P.M. Campbell, M.R. Pincus, W.B. Bowne. 2020. Anti-cancer tumor cell necrosis of multidrug resistant ovarian cancer cell lines depends on high expression of HDM-2 protein in their membranes. Ann Clin Lab Sci, 50:611-624. Pubmed
A. Thadi, L. Lewis, E. Goldstein, A. Aggarwal, M. Khalili, L. Steele, B. Polyak, S. Seydafkan, M.H. Bluth, K.A. Ward, M. Styler, P.M. Campbell, M.R. Pincus, W.B. Bowne. 2020. Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells but Not Normal Hematopoietic Cells. Anticancer Res, 40:4857-4867. Pubmed
M.C. Stout and P.M. Campbell. 2018. RASpecting the oncogene: New pathways to therapeutic advances. Biochem Pharm, 158: 217-228. Pubmed
M.C. Stout, S. Narayan, E.S. Pillet, J.S. Salvino, P.M. Campbell. 2018. Inhibition of CX3CR1 Reduces Cell Motility and Viability in Pancreatic Adenocarcinoma Epithelial Cells. Biochem Biophys Res Commun, 495:2264– 2269. PubMed
S. Lal*, E. Cheung*, M. Zarei*, R. Preet, S.N. Chand, N.C. Mambelli-Lisboa, C. Romeo, M.C. Stout, E. Londin, A. Goetz, C. Yabar, A. Nevler, C.J. Yeo, P.M. Campbell, J.M. Winter, D.A. Dixon, J.R. Brody. 2017. CRISPR knockout of the HuR gene in pancreatic and colorectal cancer cells causes a xenograft lethal phenotype. * Contributed equally. Mol Cancer Res, 15:696-707. PubMed
M.C. Stout, E. Asiimwe, J.R. Birkenstamm, S.Y. Kim, P.M. Campbell. 2014. Analyzing Ras-associated Cell Proliferation Signaling. Methods Mol Biol, 1170:393-409. PubMed
P.M. Campbell. 2014. Oncogenic Ras pushes (and pulls) cell cycle progression through ERK activation. Methods Mol Biol, 1170:155-163. PubMed
H.R. Siddique, D.J. Liao, S.K. Mishra, T. Schuster, L. Wang, B. Matter, P.M. Campbell, P. Villalta, S. Nanda, Y. Deng, M. Saleem. 2012. Epicatechin-rich cocoa polyphenol inhibits Kras-activated pancreatic ductal carcinoma cell growth in vitro and in a mouse model. Int J Cancer, 131:1720–1731. PubMed
P.M. Campbell*, N. Boufaied*, J.J. Fiordalisi, A.D. Cox, P. Falardeau, C.J. Der, H. Gourdeau. 2010. TLN-4601 suppresses growth and induces apoptosis of pancreatic carcinoma cells through inhibition of Ras-MAPK signaling. J Mol Signal, 5:18. * Contributed equally PubMed
Y. Matsuo*, P.M. Campbell*, R.A. Brekken, B. Sung, M.M. Ouellette, J.B. Fleming, B.B. Aggarwal, C.J. Der, S. Guha. 2009. K-Ras promotes angiogenesis mediated by immortalized human pancreatic epithelial cells through MAP kinase signaling pathways. Mol Cancer Res, 7:799-808. * Contributed equally. PubMed
P.M. Campbell, K.M. Lee, M.M. Ouellette, H.J. Kim, A.L. Groehler, V. Khazak, C.J. Der. 2008. Ras-driven transformation of human nestin-positive pancreatic epithelial cells. Methods Enzymol 439:451-65. PubMed
P.M. Campbell, A.L. Groehler, K.M. Lee, M.M. Ouellette, V. Khazak, C.J. Der. 2007. K-Ras promotes growth transformation and invasion of immortalized human pancreatic cells by Raf and phosphatidylinositol 3-kinase signaling. Cancer Res 67:2098-2106. PubMed
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