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 profile

Selected 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

    CMGH
    1. Seung Won Lee
    2. Taelor Ekstrom
    3. Elise C. Manalo
    4. Shangyuan Ye
    5. Mark Berry
    6. Dmytro Grygoryev
    7. Malwina Szczepaniak
    8. Jinho Lee
    9. Carlos Origel Marmolejo
    10. Syber Haverlack
    11. Juyoung Lee
    12. Vidhi M. Shah
    13. Dove Keith
    14. John L. Muschler
    15. Koei Chin
    16. Rosalie C. Sears
    17. Stuart P. Weisberg
    18. Terry Morgan
    19. Jungsun Kim
  • Suppression of dystroglycan function accompanies pancreatic acinar-to-ductal metaplasia and favours dysplasia development

    Journal of Pathology
    1. Ge Huang
    2. Luke Ternes
    3. Christian Lanciault
    4. Kevin MacPherson-Hawthorne
    5. Young Hwan Chang
    6. Rosalie C. Sears
    7. John L. Muschler
  • The polymeric fluoropyrimidine CF10 overcomes limitations of 5-FU in pancreatic ductal adenocarcinoma cells through increased replication stress

    Cancer Biology and Therapy
    1. Jennifer M. Finan
    2. Roberto Di Niro
    3. Soon Young Park
    4. Kang Jin Jeong
    5. Madeline D. Hedberg
    6. Alexander Smith
    7. Grace A. McCarthy
    8. Alex O. Haber
    9. John Muschler
    10. Rosalie C. Sears
    11. Gordon B. Mills
    12. William H. Gmeiner
    13. Jonathan R. Brody
  • Accessible high-throughput single-cell whole-genome sequencing with paired chromatin accessibility

    Cell Reports Methods
    1. Konstantin Queitsch
    2. Travis W. Moore
    3. Brendan L. O'Connell
    4. Ruth V. Nichols
    5. John L. Muschler
    6. Dove Keith
    7. Charles Lopez
    8. Rosalie C. Sears
    9. Gordon B. Mills
    10. Galip Gürkan Yardımcı
    11. Andrew C. Adey
  • A multiplex implantable microdevice assay identifies synergistic combinations of cancer immunotherapies and conventional drugs

    Nature biotechnology
    1. Zuzana Tatarova
    2. Dylan C. Blumberg
    3. James E. Korkola
    4. Laura M. Heiser
    5. John L. Muschler
    6. Pepper J. Schedin
    7. Sebastian W. Ahn
    8. Gordon B. Mills
    9. Lisa M. Coussens
    10. Oliver Jonas
    11. Joe W. Gray
  • Heterodimeric RGD-NGR PET Tracer for the Early Detection of Pancreatic Cancer

    Molecular Imaging and Biology
    1. Lingyi Sun
    2. Yongkang Gai
    3. Zhonghan Li
    4. Huiqiang Li
    5. Jianchun Li
    6. John Muschler
    7. Rui Kang
    8. Daolin Tang
    9. Dexing Zeng
  • Longitudinal analysis of human pancreatic adenocarcinoma development reveals transient gene expression signatures

    Molecular Cancer Research
    1. Jungsun Kim
    2. Taelor Ekstrom
    3. Wenli Yang
    4. Greg Donahue
    5. Dmytro Grygoryev
    6. Thuy T.M. Ngo
    7. John L. Muschler
    8. Terry Morgan
    9. Kenneth S. Zaret
  • VISTA

    Scientific Reports
    1. Luke Ternes
    2. Ge Huang
    3. Christian Lanciault
    4. Guillaume Thibault
    5. Rachelle Riggers
    6. Joe W. Gray
    7. John Muschler
    8. Young Hwan Chang
  • 3D-Imaging of Whole Neuronal and Vascular Networks of the Human Dental Pulp via CLARITY and Light Sheet Microscopy

    Scientific Reports
    1. Cristiane Miranda França
    2. Rachelle Riggers
    3. John L. Muschler
    4. Matthias Widbiller
    5. Peter Manning Lococo
    6. Anibal Diogenes
    7. Luiz Eduardo Bertassoni
  • Modeling Tumor Phenotypes In Vitro with Three-Dimensional Bioprinting

    Cell Reports
    1. Ellen M. Langer
    2. Brittany L. Allen-Petersen
    3. Shelby M. King
    4. Nicholas D. Kendsersky
    5. Megan A. Turnidge
    6. Genevra M. Kuziel
    7. Rachelle Riggers
    8. Ravi Samatham
    9. Taylor S. Amery
    10. Steven Jacques
    11. Brett C. Sheppard
    12. James E. Korkola
    13. John L. Muschler
    14. Guillaume Thibault
    15. Young Hwan Chang
    16. Joe W. Gray
    17. Sharon C. Presnell
    18. Deborah G. Nguyen
    19. Rosalie C. Sears
  • Far-Red and Near-Infrared Seminaphthofluorophores for Targeted Pancreatic Cancer Imaging

    ACS Omega
    1. Lei Wang
    2. Connor W. Barth
    3. Martha Sibrian-Vazquez
    4. Jorge O. Escobedo
    5. Mark Lowry
    6. John Muschler
    7. Haiyan Li
    8. Summer L. Gibbs
    9. Robert M. Strongin
  • Endocytic trafficking of laminin is controlled by dystroglycan and is disrupted in cancers

    Journal of Cell Science
    1. Dmitri Leonoudakis
    2. Ge Huang
    3. Armin Akhavan
    4. Jimmie E. Fata
    5. Manisha Singh
    6. Joe W. Gray
    7. John L. Muschler
  • Loss of cell-surface laminin anchoring promotes tumor growth and is associated with poor clinical outcomes

    Cancer Research
    1. Armin Akhavan
    2. Obi L. Griffith
    3. Liliana Soroceanu
    4. Dmitri Leonoudakis
    5. Maria Gloria Luciani-Torres
    6. Anneleen Daemen
    7. Joe W. Gray
    8. John L. Muschler
  • Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity

    Journal of Cell Science
    1. Dmitri Leonoudakis
    2. Manisha Singh
    3. Roozbeh Mohajer
    4. Pouya Mohajer
    5. Jimmie E. Fata
    6. Kevin P. Campbell
    7. John L. Muschler
  • 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
    1. Alain Beliveau
    2. Joni D. Mott
    3. Alvin Lo
    4. Emily I. Chen
    5. Antonius A. Koller
    6. Paul Yaswen
    7. John Muschler
    8. Mina J. Bissell
  • Sustained activation of STAT5 is essential for chromatin remodeling and maintenance of mammary-specifi c function

    Journal of Cell Biology
    1. Ren Xu
    2. Celeste M. Nelson
    3. John L. Muschler
    4. Mandana Veiseh
    5. Barbara K. Vonderhaar
    6. Mina J. Bissell
  • Nuclear translocation of β-dystroglycan reveals a distinctive trafficking pattern of autoproteolyzed mucins

    Traffic
    1. Maria Luisa Oppizzi
    2. Armin Akhavan
    3. Manisha Singh
    4. Jimmie E. Fata
    5. John L. Muschler
  • SEA domain proteolysis determines the functional composition of dystroglycan

    FASEB Journal
    1. Armin Akhavan
    2. Silvia N. Crivelli
    3. Manisha Singh
    4. Vishwanath R. Lingappa
    5. John L. Muschler
  • Regulation of clusterin expression in mammary epithelial cells

    Experimental Cell Research
    1. Yoko Itahana
    2. Marie Piens
    3. Tomoki Sumida
    4. Sylvia Fong
    5. John Muschler
    6. Pierre Yves Desprez
  • Dystroglycan loss disrupts polarity and β-casein induction in mammary epithelial cells by perturbing laminin anchoring

    Journal of Cell Science
    1. M. Lynn Weir
    2. Maria Luisa Oppizzi
    3. Michael D. Henry
    4. Akiko Onishi
    5. Kevin P. Campbell
    6. Mina J. Bissell
    7. John L. Muschler
  • Molecular recognition by LARGE is essential for expression of functional dystroglycan

    Cell
    1. Motoi Kanagawa
    2. Fumiaki Saito
    3. Stefan Kunz
    4. Takako Yoshida-Moriguchi
    5. Rita Barresi
    6. Yvonne M. Kobayashi
    7. John Muschler
    8. Jan P. Dumanski
    9. Daniel E. Michele
    10. Michael B.A. Oldstone
    11. Kevin P. Campbell
  • Proteolytic enzymes and altered glycosylation modulate dystroglycan function in carcinoma cells

    Cancer Research
    1. Jarnail Singh
    2. Yoko Itahana
    3. Selena Knight-Krajewski
    4. Motoi Kanagawa
    5. Kevin P. Campbell
    6. Mina J. Bissell
    7. John Muschler
  • CpG content affects gene silencing in mice

    Genome biology
    1. Christine Chevalier-Mariette
    2. Isabelle Henry
    3. Lucile Montfort
    4. Suzanne Capgras
    5. Sylvie Forlani
    6. John Muschler
    7. Jean François Nicolas
  • A role for dystroglycan in epithelial polarization

    Cancer Research
    1. John Muschler
    2. Dinah Levy
    3. Roseanne Boudreau
    4. Michael Henry
    5. Kevin Campbell
    6. Mina J. Bissell
  • Order and disorder

    Cancer Investigation
    1. Derek Radisky
    2. John Muschler
    3. Mina J. Bissell
  • Division 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 cell
    1. John Muschler
    2. André Lochter
    3. Calvin D. Roskelley
    4. Peter Yurchenco
    5. Mina J. Bissell
  • LagoZ and LagZ, two genes derived from the LacZ gene to study epigenetics

    Comptes Rendus de l'Academie des Sciences - Serie III
    1. Isabelle Henry
    2. Sylvie Forlani
    3. Séverine Vaillant
    4. John Muschler
    5. André Choulika
    6. Jean François Nicolas
  • Immunopurification of a sarcomeric junctional protein complex containing GAPDH

    Experimental Cell Research
    1. Kevin A. McDonald
    2. John Muschler
    3. Alan F. Horwitz