Ubiquitin Biology

Faculty

Elizabeth Floyd, Ph.D.

Z. Elizabeth Floyd, PhD

 

Research Focus

The Ubiquitin Biology laboratory is focused on understanding how the ubiquitin-proteasome pathway affects adipose tissue biology and the role of adipose tissue in obesity-related diseases such as insulin resistance and type 2 diabetes.

About this Lab

The Ubiquitin Biology Laboratory explores how ubiquitin and ubiquitin-like posttranslational protein modifications affect adipose tissue responses to the metabolic challenge of obesity.  In earlier studies, we explored how ubiquitin-dependent modifications regulate the activity of the peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor required for the formation and maintenance of adipocytes. In a series of studies, we found that the ubiquitin ligase Siah2 selectively regulates PPARgamma activity in adipose tissue while also acting to control obesity-related adipose tissue inflammation and the link between adipocyte hypertrophy and obesity-induced insulin resistance. Our current studies focus on the role of Siah2-mediated regulation of PPARγ in adipose tissue macrophage to more broadly understand how the ubiquitin-proteasome system affects the link between adipose tissue inflammation and insulin resistance.

In other studies, we found that Siah2 participates in the early steps that determine commitment of preadipocytes to adipocyte formation. That finding has led to an interest in understanding how Siah2 may affect the balance between fat and bone formation.  We also collaborate with colleagues at the Louisiana State University Health Science Center in New Orleans and the Our Lady of the Lake Regional Medical Center to explore the role of Siah2 in the ability of tumors that arise in adipose tissue (liposarcomas) to form mature fat cells as a potential therapeutic target in those cancers.

Another area of interest in the laboratory is the impact of botanical supplementation on insulin sensitivity. These studies explore the effects of extracts from Russian Tarragon and Bitter Melon, plants with a long history of ameliorating the symptoms of type 2 diabetes. In collaboration with colleagues at the University of Illinois at Chicago, we are identifying the bioactive components present in an ethanolic extract from Russian tarragon that enhance insulin signaling in skeletal muscle and improve glucose metabolism. Additional studies carried out in collaboration with colleagues in the LSU School of Engineering focus on how botanically-derived compounds affect the activity of the ubiquitin-proteasome system deubiquitinases in multiple myeloma.

 

Research In Focus

  1. Scott, M.C., Bourgeois, A., Yu, Y., Burk, D.H., Smith, B.J., Floyd, Z.E. (2023) Extract of Artemisia dracunculus L. modulates osteoblast proliferation and mineralization. Int. J Mol Sci. August 30;24(17):13423. 
  2. Smoak, P., Burke, S.J., Martin, T.M., Batdorf, H.M., Floyd, Z.E., Collier, J.J. (2022) Artemisia dracunculus L.ethanol extract and an isolated component, DMC2, ameliorate inflammatory signaling in pancreatic beta-cells via inhibition of p38 MAPK. Biomolecules May 15; 12(5):708. PMCID: PMC9139089 
  3. Dang, T.N., Tiongco, R.P., Brown, L.M., Taylor, J.L., Lyons, J.M., Lau, F.H., Floyd, Z.E. (2022) Expression of the preadipocyte marker ZFP423 is dysregulated between well-differentiated and dedifferentiated liposarcoma. BMC Cancer March 21; 22(1):300 PMCID: PMC8939188 
  4. Floyd, Z.E., Ribnicky, D.M., Raskin, I., Hsia, D.S., Rood, J.C., Gurley, B.J. (2022) Designing a clinical study with dietary supplements: It’s all in the details.  Frontiers in Nutrition.  Jan 18;8:779486.  PMCID: PMC8804374 
  5. Dang, T.N., Taylor, J.L., Kilroy, G., Yu, Y., Burk, D.H., Floyd, Z.E. (2021) Siah2 is expressed in adipocyte precursor cells and interacts with Ebf1 and Zfp521 to promote adipogenesis. Obesity. 29(1): 98-107 PMCID: PMC7902405  DOI: 10.1002/oby.23013
  6. Vandanmagsar, B., Yu, Y., Simmler, C., Dang, T.N., Kuhn, P., Poulev, A., Ribnicky, D.M., Pauli, G.F., Floyd, Z.E. (2021)  Bioactive compounds from Artemisia dracunculus L., activate AMPK signaling in skeletal muscle. Biomedicine and Pharmacotherapy, 143 (112188) PMCID: PMC8516709 
  7. Burke SJ, Taylor JL, Batdorf HM, Noland RC, Burk DH, Yu Y, Floyd ZE, Collier JJ. (2020) The Ubiquitin Ligase SIAH2 Negatively Regulates Glucocorticoid Receptor Activity and Abundance. Biomedicines Dec 30;9(1):22. PMCID: PMC7823448  DOI: 10.3390/biomedicines9010022
  8. Yu, Y., Simmler, C., Kuhn, P., Poulev, A., Raskin, I., Cefalu, W. T., Ribnicky, D., Floyd, Z.E., Pauli, G.F. (2019) The DESIGNER approach helps decipher the hypoglycemic bioactive principles of Artemisia dracunculus (Russian Tarragon). Journal of Natural Products. December 27; 82 (12): 3321-3329. PMCID: PMC7076913 DOI: 10.1021/acs.jnatprod.9b00548
  9. Ghosh, S., Taylor, J.L., Mendoza, T.M., Dang, T., Burk, D.H., Yu, Y., Kilroy, G., Floyd, Z.E. (2019) Siah2 exerts sex-dependent effects on metabolic and inflammatory remodeling in adipose tissue. BMC Biology of Sex Differences. April 15; 10(1):19. PMCID: PMC6466809 DOI: 10.1186/s13293-019-0233-y
  10. Kilroy G, Burk DH, Floyd, ZE. Siah2 mediates early events in commitment to an adipogenic pathway. Journal of Biological Chemistry. 2016; Dec 30; 291(53): 27289-27297. PMCID PMC5207155  DOI: 10.1074/jbc.M116.744672