My research focuses on determining molecular mechanisms involved in the regulation of gene expression and signal transduction pathways in cancer development and drug resistance by using high throughput sequencing technologies and cancer mouse models. I have recently identified CDK4/6 as a target for therapeutic intervention in melanoma. Therefore, I have utilized a CDK4/6 inhibitor (CDK4/6i) to suppress melanoma growth. Palbociclib is an FDA-approved CDK4/6i that has received a Breakthrough Therapy Designation and has emerged as a powerful anti-cancer therapy. It is currently being evaluated in clinical trials for many types of cancers such as melanoma, breast cancer, and glioblastoma. I am currently working on dissecting the molecular mechanisms of both intrinsic and acquired resistance to CDK4/6i in order to improve CDK4/6i based therapies and to overcome its resistance. My long-term goals are (1) to discover novel cancer therapeutics by identifying molecules and pathways that are critical for cancer development and drug resistance and (2) to improve cancer treatments by identifying druggable targets.
Akihiro Yoshida*, Yiwen Bu, Shuo Qie, John Wrangle, E. Ramsay Camp, E. Starr Hazard, Gary T. Hardiman, Renée de Leeuw, Karen E. Knudsen, and J. Alan Diehl (2019) SLC36A1-mTORC1 signaling drives acquired resistance to CDK4/6 inhibitors. Sci Adv. 5: eaax6352 * Co-corresponding author
Shuo Qie, Akihiro Yoshida, Stuart Parnham, Gyda C. Beeson, Craig C. Beeson, Adam J. Bass, Kwok-Kin Wong, Anil K. Rustgi, and J. Alan Diehl (2019) Targeting Glutamine-addiction and Overcoming CDK4/6 Inhibitor Resistance in Human Esophageal Squamous Cell Carcinoma. Nat Commun. 10: 1296
Yiwen Bu, Akihiro Yoshida, Nilesh Chitnis, Brian Altman, Amanda Taylor, Victoria Gennaro, Kent E Armeson, Steven McMahon, Chi Van Dang, Davide Ruggero, Constantinos Koumenis, Serge Y. Fuchs, and J. Alan Diehl (2018). A PERK-miR-211 axis suppresses circadian regulators and protein synthesis to promote cancer cell survival. Nat. Cell. Biol. 20: 104-115.
Akihiro Yoshida, Eric K. Lee, and J. Alan Diehl (2016). Induction of Therapeutic Senescence in Vemurafenib-Resistant Melanoma by Extended Inhibition of CDK4/6. Cancer Res. 76: 2990-3002.
Akihiro Yoshida and J. Alan Diehl (2015). CDK4/6 inhibitor: from quiescence to senescence. Oncoscience 2: 896-897
Akihiro Yoshida, Jun-ya Kato, Ikuko Nakamae, and Noriko Yoneda-Kato (2013). COP1 targets C/EBPα for degradation and induces acute myeloid leukemia via Trib1. Blood 122: 1750-1760.
Akihiro Yoshida, Noriko Yoneda-Kato, and Jun-ya Kato (2013). CSN5 specifically interacts with CDK2 and controls senescence in a cytoplasmic cyclin E-mediated manner. Sci Rep 3: 1054.
Akihiro Yoshida, Noriko Yoneda-Kato, Martina Panattoni, Ruggero Pardi, and Jun-ya Kato (2010). CSN5/Jab1 controls multiple events in the mammalian cell cycle. FEBS Lett. 584: 4545-4552.