I research cell cycle regulation, acquired resistance to CDK4/6 inhibitors, ubiquitin-dependent protein degradation, unfolded Protein Response and Tumor Progression, Non-coding RNA, and the circadian clock.
Research Information
Research Interests
Dr. Diehl’s research focuses on the molecular mechanisms of cancer initiation and progression with specific focus on the regulation of cell division and post-translational in cancer. The Diehl lab also explores the interconnections of lipid signaling, epigenetic regulation and the role of the unfolded protein response within tumor progression.
One major focus of Dr. Diehl’s research concerns the mechanisms whereby growth-signaling pathways regulate the cyclin D/CDK4/6 kinases and from this, the identification of therapeutic vulnerabilities. His current work focuses on the role of E3 ubiquitin ligases in the maintenance of cyclin D1 levels and the physiological function of the E3 ligase in tumor suppression. Additional work focuses on the regulation of novel downstream substrates of the cyclin D1/CDK4 kinase and their role in mediating cyclin D1-dependent effects on tumor cell gene expression networks. A second area of interest concerns how a stress-induced signaling pathway emanating from the endoplasmic reticulum (ER) regulates cell cycle progression, lipid biosynthesis and cell survival during tumor progression.
Publications
- Yoshida, A, Choi, J., Jin, H., Li, Y., Bajpai, S., Qie, S. and Diehl, J. A.
"Fbxl8 suppresses lymphoma growth and hematopoietic transformation through degradation of cyclin D3"
Oncogene 40:292–306 (2021) - 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). - 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). - 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). - 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). - 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). - 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).