Diabetes and metabolic disorders, organelle dysfunction, stress responses, beta cell biology
- 6260B Biochemical Sciences Building
- B.S., M.Sc., Istanbul University, School of Pharmacy, 2001 Ph.D., Baylor College of Medicine, 2007 Postdoctoral Fellow, Harvard University, 2013
- Lab Website
- Biomolecular Chemistry
- Research Interests
- Diabetes and metabolic disorders, organelle dysfunction, stress responses, beta cell biology.
- Research Fields
- Disease Biology, Cell Biology, Genomics & Proteomics, Gene Expression, Genetic Mouse Models of Human Diseases, Organelle biology, Adaptive Stress Responses
Type 1 diabetes mellitus (T1D) results from immune-mediated destruction of pancreatic β-cells leading to loss of insulin production, unsuppressed glucose production, and hyperglycemia. Despite intensive research on T1D pathogenesis, the mechanisms by which initial signals trigger autoimmunity, the identity of intracellular mediators that lead to β-cell demise and how β-cells communicate with immune cells remain poorly understood.
The ER orchestrates protein synthesis, folding and trafficking in the cell and disruption of the ER’s adaptive capacity results in activation of the UPR. Under chronic stress conditions, these UPR mediators engage many different inflammatory and stress signaling pathways that are critical for disease pathologies including insulin resistance, obesity, type2 diabetes and atherosclerosis. Although little is known about the role of ER stress and defective UPR in T1D pathogenesis emerging data suggest involvement of an abnormal UPR in β-cell pathophysiology and diabetes. However, the specific regulation, function and the significance of the distinct arms of UPR in β-cells and how β-cell ER stress can affect the function, regulation and differentiation of immune cells in the pathogenesis of T1D remain insufficiently understood.
The research in our laboratory currently focuses on detailed characterization of β-cell UPR in diabetes mouse models. We are also interested in understanding the intracellular organelle communication in the pathogenesis of diabetes as well as obesity. We believe our new research avenue will generate the basis for further mechanistic studies and will potentially translate into the development of novel and effective therapeutic strategies.
Search PubMed for more publications by Feyza Engin
1. Engin, F. “ER Stress and Development of Type 1 Diabetes” J Investig Med. 2015.
2. Brozzi, F., Nardelli, TR., Lopes, M., Millard, I., Barthson, J., Igoillo-Esteve, M., Grieco, FA., Villate, O., Oliveira, JM., Casimir, M., Bugliani, M., Engin, F., Hotamisligil, GS., Marchetti, PM., Eizirik, DL. “Cytokines induce endoplasmic reticulum stress in human, rat and mouse beta cells via different mechanisms”. Diabetologia. 2015.
3. Engin, F., Ngyuen T., Yermalovich A., Hotamisligil, GS. “Aberrant unfolded protein response in type 2 diabetes”. Sci Rep. 2014.
4. Engin, F., Yermalovich, A., Fu, W., Ngyuen, T., Hummasti, S., Decio, L., Eizirik., Mathis, D., Hotamisligil, GS. “Restoration of the unfolded protein response in pancreatic beta cells protects mice against type 1 diabetes”. Sci. Transl. Med. 2013.
5. Engin, F., Hotamisligil, GS. “Chemical modulation of ER function in metabolic diseases”. Diabetes Obes. Metab. 2010. 12 Suppl 2:108-15.
6. Yang, T., Londono, R.M., Lu, H., Li, K., Keller, B., Jiang, M.M., Chen, Y., Bertin, T., Engin, F., Dabovic, B., Rifkin, D.B., Hicks, J, Beaudet, A.L., Lee, B. “E-Selectin ligand-1 regulates growth plate homeostasis in mice by inhibiting the intracellular processing and secretion of mature TGF-”. J. Clin. Invest. 2010. 1; 120(7): 2474-85.
7. Engin, F., Lee B. “NOTCHing the bone: insights into multi-functionality”. Bone. 2010; 46(2): 274-280.
8. Engin, F., Bertin, T., Ma, O., Jiang, MM., Wang, L., Sutton, RE., Donehower, LA., Lee, B. “Notch signaling contributes to the pathogenesis of human osteosarcomas”. Hum. Mol. Genet. 2009; 18(8): 1464-1470.
9. Engin, F., Yao, Z., Yang, T., Zhou, G., Bertin, T., Jiang, M.M., Chen, Y., Wang, L., Zheng, L., Sutton, R.E., Boyce, B.F., Lee, B. “Dimorphic effects of Notch signaling in bone homeostasis”. Nat. Med. 2008; 14(3): 299-305.
10. Engin, F., Lee, B. “Understanding of human birth defects through model organisms”. (Chapter 7), in Moody, S.A, ed. Principals of Developmental Genetics. Elsevier. 2007; 129-148.
11. Zhou, G., Zheng, Q., Engin, F., Munivez, E., Chen, Y., Sebald, E., Krakow, D., Lee, B. “Dominance of SOX9 function over RUNX2 during skeletogenesis”. Proc. Natl. Acad. Sci. 2006; 103(50): 19004-9.