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Biochemistry Department - Primary Faculty

J. Alan Diehl, Ph.D.

Professor and Chair

Education

  • Ph.D.: University of Missouri, Columbia, MO
  • Postdoc: St. Jude's Research Hospital and Howard Hughes Medical Institute, Memphis, TN

Research Interests

The Diehl lab focuses on the mechanisms whereby extra-cellular signals are sensed by the cell cycle machine and are then transmitted into regulated cell cycle progression. Elucidation of these mechanisms provides a framework for understanding how growth regulatory pathways are subverted during tumor development and progression. One major focus of the laboratory are the mechanisms whereby growth-signaling pathways regulate the D-type cyclins and more specifically, how these pathways regulate accumulation of an active, nuclear cyclin D-dependent kinase in both normal and tumor cells. Our current work focuses on the role of E3 ubiquitin ligases in the maintenance of cyclin D levels and the identification of substrate networks for the ubiquitin ligases with an emphasis on how they modify tumorigenesis.

A second area of interest concerns how a stress-induced signaling pathway emanating from the endoplasmic reticulum (ER) regulates circadian rhythms, non-coding RNA expression, and cell survival during tumor progression. Mammalian cells contain two transmembrane protein kinases (PERK and Ire1) that function as proximal signal transducers to coordinate protein synthesis, with circadian rhythms, cell division, and cell fate. The Diehl laboratory currently focuses on how non-coding RNAs regulate ER stress and circadian clock oscillations during tumor development and progression.

Selected References

  • Yoshida A., Bu B., Qie S., Wrangle J., Cam E. R., Hazard E. S., Hardiman G., Leeuw R., Knudsen K. E., and Diehl J. A.
    “SLC36A1-mTORC1 signaling drives acquired resistance to CDK4/6 inhibitors”
    Science Advances 5 (9): eaax6352 (2019).
  • Qie S., Yoshida A., Parnham S., Oleinik N., Beeson G. C., Beeson C. C., Ogretmen B., Bass A. J., Wong K. K., Rustgi A. K., and Diehl J. A.
    “Targeting glutamine-addiction and overcoming CDK4/6 inhibitor resistance in human esophageal squamous cell carcinoma”
    Nat Commun 10 (1): 1296 (2019). Read article in PubMedCentral
  • Qie S. and Diehl J. A.
    “Glutamine addiction: an Achilles heel in esophageal cancers with dysregulation of CDK4/6”
    Mol Cell Oncol 6 (4): 1610257 (2019). Read article in PubMedCentral
  • Bu Y., Yoshida A., Chitnis N., Altman B. J., Tameire F., Oran A., Gennaro V., Armeson K. E., McMahon S. B., Wertheim G. B., Dang C. V., Ruggero D., Koumenis C., Fuchs S. Y., and Diehl J. A.
    “A PERK-miR-211 axis suppresses circadian regulators and protein synthesis to promote cancer cell survival”
    Nat Cell Biol 20 (1): 104-15 (2018). Read article in PubMedCentral
  • Qie S., Majumder M., Mackiewicz K., Howley B. V., Peterson Y. K., Howe P. H., Palanisamy V., and Diehl J. A.
    “Fbxo4-mediated degradation of Fxr1 suppresses tumorigenesis in head and neck squamous cell carcinoma”
    Nat Commun 8 (1): 1534 (2017). Read article in PubMedCentral
  • Yoshida A., Lee E. K., and Diehl J. A.
    “Induction of Therapeutic Senescence in Vemurafenib-Resistant Melanoma by Extended Inhibition of CDK4/6”
    Cancer Res 76 (10): 2990-3002 (2016). Read article in PubMedCentral
  • Xu Z., Bu Y., Chitnis N., Koumenis C., Fuchs S. Y., and Diehl J. A.
    “miR-216b regulation of c-Jun mediates GADD153/CHOP-dependent apoptosis”
    Nat Commun 7: 11422 (2016). Read article in PubMedCentral
  • Pytel D., Gao Y., Mackiewicz K., Katlinskaya Y. V., Staschke K. A., Paredes M. C., Yoshida A., Qie S., Zhang G., Chajewski O. S., Wu L., Majsterek I., Herlyn M., Fuchs S. Y., and Diehl J. A.
    “PERK Is a Haploinsufficient Tumor Suppressor: Gene Dose Determines Tumor-Suppressive Versus Tumor Promoting Properties of PERK in Melanoma”
    PLoS Genet 12 (12): e1006518 (2016). Read article in PubMedCentral
  • Li Y., Chitnis N., Nakagawa H., Kita Y., Natsugoe S., Yang Y., Li Z., Wasik M., Klein-Szanto A. J., Rustgi A. K., and Diehl J. A.
    “PRMT5 is required for lymphomagenesis triggered by multiple oncogenic drivers”
    Cancer Discov 5 (3): 288-303 (2015). Read article in PubMedCentral
J. Alan Diehl Faculty's publications at pubmed