Derek Abbott graduated from the University of Virginia in 1993. He then matriculated to Vanderbilt University School of Medicine as an MSTP Student. While a graduate student, he studied the breast cancer genes BRCA1 and BRCA2, ultimately attaining a Ph.D. in Cell Biology. After completion of his medical school requirements, Dr. Abbott continued his clinical training in Anatomic Pathology at Brigham and Women's Hospital (Harvard Medical School) in Boston, MA. After completing his residency and board certification, Dr. Abbott joined the lab of Dr. Lewis Cantley in the Department of Systems biology at Harvard Medical School. While in Lew Cantley's lab, Dr. Abbott began deciphering the signal transduction cascade initiated by bacterial activation of the Crohn's Disease susceptibility protein, NOD2.
Dr. Abbott joined the Case Western Reserve University's Department of Pathology in the fall of 2006. He is currently the Arline and Curtis F. Garvin Professor of Medicine, a Professor of Pathology and the co-director of the CWRU Medical Scientist Training Program. Current interests in the lab include genotype:phenotype correlations in inflammatory disease, drug development in genetic inflammatory disease and synthetic biology approaches to translational medicine. Outside of lab, he's quite busy keeping up with his wife, Dr. Kathryn Teng – Service Line Director and the Division Chief of General Internal Medicine at MetroHealth and his two children, Annabelle and Nate.
The last decade has seen an explosion in our ability to understand the genetics of disease. While we are able to generate genetic data in disease quickly, an important bottleneck lies in the understanding of genetic mutations’ role in disease. My lab utilizes cutting-edge cell editing technology, synthetic biology and chemical biology to understand mutations role in disease and to better understand key genetic nodal points for translational innovation. This approach has led to the discovery of novel inhibitors of the inflammatory disease kinase, RIPK2, and more recently to novel mechanisms to inhibit the pyroptotic pore protein, Gasdermin D. Both of these pharmaceutical intervention show efficacy in inflammatory diseases as diverse as Inflammatory Bowel Disease, Psoriasis, Sarcoidosis and Sepsis.
Representative Publications (last 5 years):
Chirieleison, S.M., Rathkey, J.R. and D.W. Abbott*. (2018) “Unique BIR domain sets dictate IAP-driven cell-death and NOD2 signal specificity.” Science Signaling. in press. *corresponding author
Yang, J., Liu, Z., Want, C., Yang, R., Rathkey, J.K. Shi, W., Dubyak, G.R., Abbott, D.W., and T.S. Xiao. (2018) Mechanism of gasdermin D recognition by inflammatory caspases and their 2 inhibition by a gasdermin D-derived peptide inhibitor, PNAS. Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):6792-6797. doi: 10.1073/pnas.1800562115. Epub 2018 Jun 11.
Liu, Z, Wang, C., Rathkey, J.K., Yang, J., Dubyak, G.R., Abbott, D.W. and T.S. Xiao. (2018) Structures of the Gasdermin D C-Terminal Domains Reveal Mechanisms of Autoinhibition. Structure. 26: 778-84.
Dziedzic, S.A., Su, Z., Najafov, A., Amin, P., Pan, H., Sun, L., Zhu, H., Abbott, D.W. and J. Yuan. (2018) “ABIN-1 Regulates RIPK1 Activation by Controlling Its Ubiquitination in TNFR1 Signaling.” Nature Cell Biology, 20:58-68.
Perez, J.M., Chen, Y. Xiao, T.S. and D.W. Abbott* (2018) “Phosphorylation of the E3 ubiquitin protein ligase ITCH diminishes binding to its cognate E2 ubiquitin ligase.” Journal of Biological Chemistry, 293:1100-1105.*corresponding author
Rathkey, J.K., Benson, B.L, Chirieleison, S.M., Yang, J., Xiao, T.S., Dubyak, G.R., Huang, A.Y. and D.W. Abbott*. (2017) Live-cell visualization of gasdermin D-driven pyroptotic cell death. Journal of Biological Chemistry. 292:14649-14658. *corresponding author
Chirieleison, S.M., Marsh, R., Kumar, P., Rathkey, J.K., Dubyak, G.R. and D.W. Abbott*. (2017) Nucleotide-binding oligomerization domain (NOD) signaling defects and cell death susceptibility cannot be uncoupled in X-linked inhibitor of apoptosis (XIAP)-driven inflammatory disease. J Biol Chem. 2017 Jun 9;292(23):9666-9679. doi: 10.1074/jbc.M117.781500. Epub 2017 Apr 12. *corresponding author
Chirieleison, S.M., Kertesy, S.B. and D.W. Abbott* (2016) “Synthetic Biology Reveals the Uniqueness of the RIP Kinase Domain”. Journal of Immunology, 96:4291-7. *corresponding author
Petrosiute,A., Dorand, R.D., Nthale, J., Myers, J.T., Barkauskas, D.S., Chirieleison, S.M.,Pareek, T., Abbott, D.W., Stearns, D.S., Letterio, J.J., and A.Y. Huang. (2016) “Cdk5 Disruption Attenuates Tumor PD-L1 Response to IFN Leading to CD4+ T-cell Mediated Rejection” Science, 53: 399-403.
Russo, H, Rathkey, J., Boyd-Tressler, A., Katsnelson, M.A., Abbott, D.W. and G.R. Dubyak. (2016) “Active caspase-1 induces gasdermin D-dependent plasma membrane pores that are blocked by lanthanides”, Journal of Immunology, 197: 1353-67.
Perez, J.M., Chirieleison, S.M. and D.W. Abbott* (2015) “An I Kappa Kinase-regulated feed-forward circuit prolongs inflammation.” Cell Reports, 12:537-544 *corresponding author
Tigno-Aranjuez, J.T., Benderitter, P., Rombouts,F., Deroose, F., Bai, X., Mattioli, B., Cominelli, F., Pizarro, T.T., Hoflack, J., and D.W. Abbott* (2014) “In vivo inhibition of RIPK2 kinase alleviates inflammatory disease.” J. Biol. Chem., 289: 29651-29654. *corresponding author
Jun, J.C., Kertesy, S., Jones, M.B., Marinis, J.M., Cobb, B.A., Tigno-Aranjuez, J.T. and D.W. Abbott*. (2013) Innate immune-directed NF-κB signaling requires site-specific NEMO ubiquitination. Cell Reports, 4:352-361, *corresponding author