Buckley Lab
The Buckley Lab investigates how dysregulation of the ubiquitin–proteasome system (UPS) drives hematologic malignancies and bone marrow failure syndromes, with a focus on ubiquitin E3 ligases as key regulators of hematopoietic stem and progenitor cell (HSPC) fate, genome stability, and oncogenic signaling. A central theme of the lab is defining how aberrant protein ubiquitylation alters signaling pathways such as PI3K, DNA damage responses, cell cycle control, and RNA splicing to promote leukemogenesis and lymphomagenesis. Using integrated genetic, proteomic, and multi-omics approaches in human samples and innovative mouse models, the lab studies the roles of E3 ligases including FBXO21, UBR5, and FBXL6 in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and mantle cell lymphoma (MCL). The Buckley Lab also has a strong translational focus, developing targeted therapeutic strategies—such as small-molecule inhibitors and PROTACs—that selectively disrupt oncogenic ubiquitin signaling while sparing normal hematopoiesis. Through these efforts, the lab aims to uncover fundamental mechanisms of hematopoietic regulation and identify novel, mechanism-based therapies for aggressive and treatment-resistant blood cancers.
Shannon Buckley, PhD
Associate Professor
University of Utah
Dept. of Internal Medicine
Div. of Hematology and Hematopoietic Malignancies
Shannon.Buckley@hci.utah.edu
Kasidy Dobish, PhD
Assistant Professor
University of Utah
Department of Neurobiology
Kasidy.Weber@hci.utah.edu
Shihai Jia, PhD
Research Associate
University of Utah
Dept. of Internal Medicine
Div. of Hematology and Hematopoietic Malignancies
Shihai.Jia@hci.utah.edu
Deborah Kajewole, PhD
Postdoctoral Fellow
University of Utah
Dept. of Internal Medicine
Div. of Hematology and Hematopoietic Malignancies
Deborah.Kajewole@hci.utah.edu
Paulina Jaimes
Graduate Student
University of Utah
Dept. of Oncological Sciences
Div. of Hematology and Hematopoietic Malignancies
Paulina.Jaimes@hci.utah.edu
Hui Huang
Graduate Student
University of Utah
Dept. of Internal Medicine
Div. of Hematology and Hematopoietic Malignancies
Hui.Huang@hci.utah.edu
Laura Mims, DO
Medical Fellow
University of Utah
Dept. of Pediatrics
Div. of Hematology and Hematopoietic Malignancies
Laura.Mims@hsc.utah.edu
Hank Peters
Senior Lab Specialist
University of Utah
Dept. of Internal Medicine
Div. of Hematology and Hematopoietic Malignancies
Hank.Peters@hci.utah.edu
Kate Hansen
Lab Specialist
University of Utah
Dept. of Internal Medicine
Div. of Hematology and Hematopoietic Malignancies
u1304173@utah.edu
Danielle Alvarado
Lab Specialist
University of Utah
Dept. of Internal Medicine
Div. of Hematology and Hematopoietic Malignancies
Danielle.Alvarado@hci.utah.edu
Josh Hutchins
Lab Specialist
University of Utah
Dept. of Internal Medicine
Div. of Hematology and Hematopoietic Malignancies
Josh.Hutchins@hci.utah.edu
Tyler Thompson
Undergraduate Researcher
University of Utah
Dept. of Internal Medicine
Div. of Hematology and Hematopoietic Malignancies
Tyler.Thompson@hci.utah.edu
Cassandra Burdick
Undergraduate Researcher
current: Graduate Student at BYU
Bea Winship
Senior Lab Specialist
current: Lab manager on the east coast
Tieker Duncan-Silas
Lab Specialist
Current: Medical School
Dalton Bean
Master's Student
Current: Heathtree
Cathy Gaville
Postdoctoral Fellow
Current:
Karli Wittorf
PhD Student
Current: Assistant Professor, Creighton University
Tyler Gilbreath
PhD Student
Current:
Samantha Swenson
Postdoctoral Fellow
Current: Instructor at UNMC
Mika Caplan
Undergraduate Student
Current: PhD student UCSD
Willow Hynes-Smith
PhD 2019
Current:
(Selected Publications Since 2010)
- Swenson SA, Dobish KK, Peters HC, Winship CB, Hynes-Smith RW, Caplan M, Wittorf KJ, Ghosal G, Buckley SM . (2024). Ubiquitin E3 ligase FBXO9 regulates pluripotency by targeting DPPA5 for ubiquitylation and degradation, Stem Cells. 2024 Apr 15;42(4):317-328. doi: 10.1093/stmcls/sxae004 .
- Dobish KK, Wittorf KJ, Swenson SA, Bean, DC, Gavile, CM, Woods NT, Ghosal, G, Hyde RK, Buckley SM . (2023). FBXO21 mediated degradation of p85 regulates proliferation and survival of acute myeloid leukemia. Leukemia. 2023 Nov;37(11):2197-2208.
- Wittorf KJ, Weber KK, Swenson SA, Buckley SM Ubiquitin E3 ligase FBXO21 regulates cytokine-mediated signaling pathways, but is dispensable for steady-state hematopoiesis. Experimental Hematology 114, 33-42 (2022). https://doi.org/10.1016/j.exphem.2022.08.002
- Caplan M, Wittorf KJ, Weber KK, Swenson SA, Gilbreath TJ, Hynes-Smith RW, Amador C, Hyde RK, and Buckley, SM. Multi-omics reveals mitochondrial metabolism proteins susceptible for drug discovery in AML. Leukemia 36, 1296–1305 (2022). https://doi.org/10.1038/s41375-022-01518-z
- Hynes-Smith, RW, Wittorf KJ, Buckley, SM. Regulation of normal and malignant hematopoiesis by FBOX ubiquitin E3 ligases. Trends in Immunology. 2020.
- Swenson, SA., Gilbreath, TJ., Vahle, H., Hynes-Smith, RW., Law, HCH., Woods, NT., Green, MR., Buckley, SM. UBR5 HECT domain mutations identified in mantle cell lymphoma control maturation of B cells. Blood. 2020;136(3):299-312. doi:10.1182/blood.2019002102.
- Hynes-Smith, RW., Swenson, SA., Vahle, H., Wittorf, KJ., Caplan, Amador, C., Hyde, RK., Buckley, SM. Loss of FBXO9 enhances proteasome activity and promotes aggressiveness in acute myeloid leukemia. Cancers 2019, 11(11), 1717; https://doi.org/10.3390/cancers11111717
- Gao, J*, Buckley, SM*, Cimmino L, Guillamot M, Strikoudis A, Cang Y, Goff SP, Aifantis I. The CUL4-DDB1 ubiquitin ligase complex controls adult and embryonic stem cell differentiation and homeostasis. Elife. 2015 Nov 27;4. pii: e07539. doi: 10.7554/eLife.07539. PubMed PMID: 26613412. (*contributed equally to the manuscript)
- Reavie, LR.*, Buckley, SM.*, Loizou, E, Takeishi, S., Abdel-Wahab, O., Aranda-Orgilles, B., Ndiaye-Lobry, D., Ibrahim, S., Nakayama, KI., and Aifantis, I. Regulation of c-Myc ubiquitination controls chronic myelogenous leukemia initiation and progression. Cancer Cell. 2013; 23(3):362-375. (*contributed equally to the manuscript)
- Buckley, SM., Aranda-Orgilles, B., Strikoudis, A., Apostolou, E., Loizou, E., Moran-Crusio, K., Farnsworth, CL., Koller, AA., Dasgupta, R., Silva, JC., Stadtfeld, M., Hochedlinger, K., Chen, EI., and Aifantis, I. Regulation of pluripotency and cellular reprogramming by the ubiquitin-proteasome system. Cell Stem Cell. 2012; 11(6):783-798. Comment in: Cell Stem Cell. 2013; 11(6):728-730. UPS Delivers Pluripotency. Okita, Y. and Nakayama, K.
- Buckley, S. and Verfaillie, C. Regulation of Hematopoiesis. In: Blood and Bone Marrow Pathology, 2nd ed. Elsevier, 63-76, 2011.
- Buckley, SM., Ulloa-Montoya, F., Abts, D., Oostendorp, R., Dzierzak, E., Ekker, SC. and Verfaillie, CM. Maintenance of HSC by Wnt5a secreting AGM-derived stromal cell line. Experimental Hematology. 2011; 39(1):114-123.
- Reavie, L., Della Gatta, G., Crusio, K., Aranda-Orgilles, B., Buckley, SM., Thompson, B., Lee, E., Gao, J., Bredemeyer, AL., Helmink, BA., Zavadil, J., Sleckman, BP., Palomero, T., Ferrando, A., and Aifantis, I. Regulation of Hematopoietic Stem Cell Differentiation by a Single Ubiquitin Ligase-Substrate Complex. Nature Immunology. 2010; 11(3):207-15.
2024
(September) Kasidy defended her thesis! Congratulations Dr. Dobish!
2023
Congratulations Sam, Kasidy, and Karli for their publications in Leukemia and Stem Cells!
2022
(August) Tyler and Karli graduated! Congratulations Dr. Gilbreath and Dr. Wittorf!
(August) Big news, the Buckley Lab moved to the University of Utah in the Huntsman Cancer Institute
(January) Shannon received the Joseph P. and Harriet K. Gilmore Distinguished New Investigator Award and UNMC New Investigator Award
2021
(January) Shannon is selected as 2021 ASH scholar
(August) The Buckley Lab is now funded by an NIH NCI R37 and NIAID R01 award!
2020
(December) Willow and Karli publish a review in Trends in Immunology
(July) Tyler and Karli are awarded UNMC graduate fellowships
(May) Mika graduates with honors at UNL and is off to start her PhD at UCSD
(April) Sam and Tyler's manuscript is accepted in Blood!
2019
(December) Willow defends her thesis. Congrats, Dr. Hynes-Smith!
We are looking for undergraduate students, and graduate students interested in studying the role of the ubiquitin proteasome systems in regulating normal and maliganant hematopoiesis. If interested in our research please email me at Shannon.Buckley@hci.utah.edu with your CV/Resume.
