Shannon M. Buckley

Shannon M. Buckley, PhD

Languages spoken: English

Academic Information

Departments Adjunct - Oncological Sciences , Adjunct - Biochemistry , Primary - Internal Medicine

Divisions: Hematology & Hematologic Malignancies

Academic Office Information

Shannon.Buckley@hci.utah.edu

Lab

The goal of my lab is to utilize genomic and proteomic approaches in normal and malignant hematopoietic cells to study molecular mechanisms regulating cell fate decisions. Our research specially focuses on studying posttranslational modifications by ubiquitin E3 ligases in self-renewal, differentiation, and transformation. Adult hematopoiesis is maintained throughout life by the hematopoietic stem cell (HSC), which are self-renewing population capable of generating all hematopoietic lineages. Within the bone marrow (BM) the HSCs are quiescent and can signaled to replenish the hematopoietic system in times of stress. Both intrinsic and extrinsic molecular mechanisms such as cytokine signaling and transcription factors play a key role in quiescence, self-renewal, and differentiation. In addition, the ubiquitin proteasome system (UPS), a key modulator of protein stability and function, regulates cell fate decisions adding an additional layer to molecular mechanisms regulating hematopoiesis. Ubiquitin E3 ligases are the substrate-recognizing component of the UPS that target specific proteins, tags them with polyubiquitin chains, and promotes their degradation through the proteasome. One family of E3 ligases is the FBOX family of proteins, which contains about 71 E3 ligases. To date only 15 of the 71 FBOX proteins have a known role in normal or malignant hematopoiesis. We are currently studying a number of FBOX proteins to understand their role in HSC maintenance, differentiation, and malignant transformation.

We also are studying the ubiquitin E3 ligase UBR5. UBR5 is mutated in ~18% of patients with Mantle Cell Lymphoma (MCL). Our work has demonstrated a key role of UBR5 in maturation and activation of B cells, and our future goal is to decipher the molecular mechanism of UBR5 in B cell activation and lymphoma. In addition, we have utilized proteomic approaches to identify key proteins expressed in MCL patients with the goal of identifying potential therapeutic targets. The dynamic reversibility of the ubiquitin modification (by kinases, phosphatases, E3 ligases and de-ubiquitinases) and recent success of a UPS inhibitor (Velcade) for the treatment of multiple myeloma and mantle cell lymphoma proves the translational importance of the UPS system. The UPS is amenable to molecule targeting, opening the way for possible future therapeutics. This suggests that targeting of specific elements of the UPS could lead to future breakthroughs in both basic research and cancer therapy by leading to more efficient generation of induced pluripotent stem cells, promoting lineage differentiation for cell therapy, and provide potential targets for drug discovery. Building from our current projects we aim to further explore the role of ubiquitin proteasome system in regulating self-renewal, differentiation, and malignant transformation by utilizing both proteomic and genomic approaches in normal and malignant hematopoietic populations.

Education History

Undergraduate University of St. Thomas - Minnesota
 BA
Graduate Training University of Minnesota
 PhD
Fellowship New York University School of Medicine
 Postdoctoral Research Fellow

Selected Publications

Journal Article

  1. Qiao F, Law HC, Krieger KL, Clement EJ, Xiao Y, Buckley SM, Woods NT (2021). Ctdp1 deficiency leads to early embryonic lethality in mice and defects in cell cycle progression in MEFs. Biol Open, 10(1).
  2. Swenson SA, Gilbreath TJ, Vahle H, Hynes-Smith RW, Graham JH, Law HC, Amador C, Woods NT, Green MR, Buckley SM (2020). UBR5 HECT domain mutations identified in mantle cell lymphoma control maturation of B cells. Blood, 136(3), 299-312.
  3. Ma MCJ, Tadros S, Bouska A, Heavican T, Yang H, Deng Q, Moore D, Akhter A, Hartert K, Jain N, Showell J, Ghosh S, Street L, Davidson M, Carey C, Tobin J, Perumal D, Vose JM, Lunning MA, Sohani AR, Chen BJ, Buckley S, Nastoupil LJ, Davis RE, Westin JR, Fowler NH, Parekh S, Gandhi M, Neelapu S, Stewart D, Bhalla K, Iqbal J, Greiner T, Rodig SJ, Mansoor A, Green M (2022). Subtype-specific and co-occurring genetic alterations in B-cell non-Hodgkin lymphoma. Haematologica, 107(3), 690-701.
  4. Caplan M, Wittorf KJ, Weber KK, Swenson SA, Gilbreath TJ, Willow Hynes-Smith R, Amador C, Hyde RK, Buckley S (2022). Multi-omics reveals mitochondrial metabolism proteins susceptible for drug discovery in AML. Leukemia, 2022 May;36(5):1296-1305., 36(5), 1296-1305.
  5. Wittorf KJ, Weber KK, Swenson SA, Buckley S (2022). Ubiquitin E3 ligase FBXO21 regulates cytokine-mediated signaling pathways, but is dispensable for steady-state hematopoiesis. Experimental hematology, 114, 33-42.e3.
  6. 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, 37(11), 2197-2208.
  7. Swenson SA, Wittorf KJ, Winship CB, Law HC, Vose JM, Greiner T, Green MR, Woods NT, Buckley SM (2026). Proteome landscape of B cell malignancies identifies mantle cell lymphoma specific signature. bioRxiv,
  8. 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, 2024;, sxae004. Stem cells (Dayton, Ohio),
  9. 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,
  10. Swenson SA, Dobish KK, Peters HC, Bea Winship C, Willow Hynes-Smith R, Caplan M, Wittorf KJ, Ghosal G, Buckley S (2024). Ubiquitin E3 Ligase FBXO9 Regulates Pluripotency by Targeting DPPA5 for Ubiquitylation and Degradation. Stem cells (Dayton, Ohio), 42(4), 317-328.
  11. Dobish KK, Wittorf KJ, Swenson SA, Bean DC, Gavile CM, Woods NT, Ghosal G, Hyde RK, Buckley S (2023). FBXO21 mediated degradation of p85¿ regulates proliferation and survival of acute myeloid leukemia. Leukemia, 37(11), 2197-2208.
  12. Arjun Dhir, Alexander Ethell, Riley Watkins, Calvin Lam, Kevin Tur-Rodriguez, Jimmie Persinger, Kasidy Dobish, Sipra Panda, Shannon Buckley, Samantha Swenson, Sandipan Brahma, M. Jordan Rowley, and R. Katherine Hyd (2025). The Splicing Factor PTBP1 Interacts with RUNX1 and is Required for Leukemia Cell Survival. Leukemia,
  13. Dhir A, Ethell A, Watkins R, Lam C, Tur-Rodriguez K, Persinger J, Dobish KK, Panda S, Buckley SM, Swenson SA, Brahma S, Rowley MJ, Hyde R (2026). The splicing factor PTBP1 interacts with RUNX1 and is required for leukemia cell survival. Leukemia, 40(1), 138-151.

Review

  1. Hynes-Smith RW, Wittorf KJ, Buckley SM (2020). Regulation of Normal and Malignant Hematopoiesis by FBOX Ubiquitin E3 Ligases. [Review]. Trends Immunol, 41, (12), 1128-1140.

Abstract

  1. Weber K, Wittorf K, Swenson S, Buckley S (2022). Investigating the Role of Ubiquitin E3 Ligase, FBXO21, in the Regulation of Cytokine Signaling within Acute Myeloid Leukemia. 111(Supplement), 3221.
  2. Wittorf K, Weber K, Swenson S, Buckley S (2022). The Role of Ubiquitin E3 Ligase FBXO21 in Regulating Hematopoietic Stem and Progenitor Cells (HSPC Through Cytokine Mediated Pathways). 111(Supplement), 3226.
  3. Swenson S, Gilbreath T, Reznicek T, Buckley S (2022). Using Quantitative Proteomics to Identify New Therapeutic Targets in Mantle Cell Lymphoma. 111(Supplement), 3200.
  4. Caplan M, Hynes-Smith W, Swenson S, Gilbreath T, Reznicek T, Buckley S (2022). Identifying Protein Expression Changes in Acute Myeloid Leukemia. 34(Supplement S1),
  5. Bean D, Weber K, Winship C, Peters H, Gavile C, Buckley (2023). Investigating the Role of Ubiquitin E3 Ligase, UBR5, in Myeloid Malignancies. Experimental Hematology, 124 (Supplement), S62. S62.,
  6. Weber K, Wittorf K, Swenson S, Bean D, Peters H, Hyde RK, Buckley S (2023). Investigating the Role of Ubiquitin E3 Ligase, FBXO21, in Cytokine Mediated Signaling within Acute Myeloid Leukemia. Experimental Hematology, 124 (Supplement), S158.
  7. Bean D, Weber K, Winship C, Peters H, Gavile C, Buckley (2023). Investigating the Role of Ubiquitin E3 Ligase, UBR5, in Myeloid Malignancies. Experimental Hematology, 124 (Supplement), S62.

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