John L. Muschler, Ph.D.
- Research Associate Professor of Biomedical Engineering, School of Medicine
Biography
My primary research focus for most of the last 20 years has been the study of extracellular matrix (ECM) receptor signaling in the context of normal epithelial cell biology and cancer progression, using both cell culture and transgenic mouse models. My motivation has been to understand the mechanisms coordinating the development and function of cells within tissues, and to understand how alterations in these mechanisms contribute to diseases, such as cancers.
My laboratory’s efforts have revealed the roles of specific ECM proteins and receptors in the control of epithelial tissue architecture (apico-basal polarity) and growth. These studies highlighted the importance of ECM assembly and endocytic trafficking processes in the control of epithelial architecture and function. They have also provided insights into the alteration of these processes in cancers, revealing novel changes in post-translational protein modifications arising with cancer progression that lead to changes in ECM assembly and protein trafficking.
My studies of endocytic trafficking have sparked a strong interest in generating cancer-targeting agents and their value for selectively delivering therapeutic agents, or imaging agents, to the interior of cancer cells.
More recently, as a member of the Oregon Center for Spatial Systems Biomedicine (OCSSB) I have developed a strong interest in new methods of 3D cancer imaging in intact tissues using light sheet microscopy, and have been pioneering the application of these new tissue clearing, staining, and imaging technologies to the study of cancer progression.
Education and training
Memberships and associations:
- OHSU Center for Spatial System Biomedicine
Areas of interest
- My research has focused on ECM receptor signaling in the context of normal cell biology and human disease, and the generation of unique reagents and methods for the dissection of these pathways.
Publications
Elsevier pure profileSelected publications
- Leonoudakis D, Huang G, Akhavan A, Fata JE, Singh M, Gray JW, Muschler JL. Endocytic trafficking of laminin is controlled by dystroglycan and is disrupted in cancers. J Cell Sci. 2014 Nov 15;127(Pt 22):4894-903. PubMed PMID: 25217627; PubMed Central PMCID: PMC4231305.
- Leonoudakis, D., Singh, M., Mohajer, R., Mohajer, P., Fata, J.E., Campbell, K.P., Muschler, J.L. (2010). Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity. J. Cell Science.
- Beliveau, A., Mott, J.D., Lo., A, Chen, E.I.2, Koller, A.A., Yaswen, P., Muschler, J.L. and Bissell, M.J. (2010) Raf-induced MMP9 Disrupts Tissue Architecture of Human Breast Cells in Three-Dimensional Culture and is Necessary for Tumor Growth in vivo. Genes and Development 24:2800-11.
- Muschler, J.L., Streuli, C.H. (2010). Cell-matrix interactions in mammary gland development and breast cancer. In Mammary Gland Biology. Cold Spring Harb Perspect Biol doi: 10.1101/cshperspect.a003202.
- Xu, R., Nelson, C.M., Muschler, J.L., Veiseh, M., Vonderhaar, B.K., Bissell, M.J. (2009). Sustained activation of STAT5 is essential for chromatin remodeling and maintenance of mammary-specific function. J. Cell Biology. 184:57-66.
Publications
HMG Box-containing Protein 1 (HBP1) Protects Against Pancreatic Injury in Acute Pancreatitis but Promotes Neoplastic Progression
CMGHSuppression of dystroglycan function accompanies pancreatic acinar-to-ductal metaplasia and favours dysplasia development
Journal of PathologyThe polymeric fluoropyrimidine CF10 overcomes limitations of 5-FU in pancreatic ductal adenocarcinoma cells through increased replication stress
Cancer Biology and TherapyAccessible high-throughput single-cell whole-genome sequencing with paired chromatin accessibility
Cell Reports MethodsA multiplex implantable microdevice assay identifies synergistic combinations of cancer immunotherapies and conventional drugs
Nature biotechnologyHeterodimeric RGD-NGR PET Tracer for the Early Detection of Pancreatic Cancer
Molecular Imaging and BiologyLongitudinal analysis of human pancreatic adenocarcinoma development reveals transient gene expression signatures
Molecular Cancer ResearchVISTA
Scientific Reports3D-Imaging of Whole Neuronal and Vascular Networks of the Human Dental Pulp via CLARITY and Light Sheet Microscopy
Scientific ReportsModeling Tumor Phenotypes In Vitro with Three-Dimensional Bioprinting
Cell ReportsFar-Red and Near-Infrared Seminaphthofluorophores for Targeted Pancreatic Cancer Imaging
ACS OmegaEndocytic trafficking of laminin is controlled by dystroglycan and is disrupted in cancers
Journal of Cell ScienceLoss of cell-surface laminin anchoring promotes tumor growth and is associated with poor clinical outcomes
Cancer ResearchDystroglycan controls signaling of multiple hormones through modulation of STAT5 activity
Journal of Cell ScienceRaf-induced MMP9 disrupts tissue architecture of human breast cells in three-dimensional culture and is necessary for tumor growth in vivo
Genes and DevelopmentSustained activation of STAT5 is essential for chromatin remodeling and maintenance of mammary-specifi c function
Journal of Cell BiologyNuclear translocation of β-dystroglycan reveals a distinctive trafficking pattern of autoproteolyzed mucins
TrafficSEA domain proteolysis determines the functional composition of dystroglycan
FASEB JournalRegulation of clusterin expression in mammary epithelial cells
Experimental Cell ResearchDystroglycan loss disrupts polarity and β-casein induction in mammary epithelial cells by perturbing laminin anchoring
Journal of Cell ScienceMolecular recognition by LARGE is essential for expression of functional dystroglycan
CellProteolytic enzymes and altered glycosylation modulate dystroglycan function in carcinoma cells
Cancer ResearchCpG content affects gene silencing in mice
Genome biologyA role for dystroglycan in epithelial polarization
Cancer ResearchOrder and disorder
Cancer InvestigationDivision of labor among the α6β4 integrin, β1 integrins, and an E3 laminin receptor to signal morphogenesis and β-casein expression in mammary epithelial cells
Molecular biology of the cellLagoZ and LagZ, two genes derived from the LacZ gene to study epigenetics
Comptes Rendus de l'Academie des Sciences - Serie IIIImmunopurification of a sarcomeric junctional protein complex containing GAPDH
Experimental Cell Research