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):
Liu Z, Wang C, Yang J, Chen Y, Zhou B, Abbott DW, Xiao TS (2020). Caspase-1 Engages Full-Length Gasdermin D through Two Distinct Interfaces That Mediate Caspase Recruitment and Substrate Cleavage. Immunity. 2020 Jul 14;53(1):106-114.e5. doi: 10.1016/j.immuni.2020.06.007. Epub 2020 Jun 17. PMID: 32553275
Karmakar M, Minns M, Greenberg EN, Diaz-Aponte J, Pestonjamasp K, Johnson JL, Rathkey JK, Abbott DW, Wang K, Shao F, Catz SD, Dubyak GR, Pearlman E (2020). N-GSDMD trafficking to neutrophil organelles facilitates IL-1β release independently of plasma membrane pores and pyroptosis. Nat Commun. 2020 May 5;11(1):2212. doi: 10.1038/s41467-020-16043-9. PMID: 32371889. PMCID: PMC7200749
Rathkey JK, Xiao TS, Abbott DW (2020). Human polymorphisms in GSDMD alter the inflammatory response. J Biol Chem. 2020 Mar 6;295(10):3228-3238. doi: 10.1074/jbc.RA119.010604. Epub 2020 Jan 27. PMID: 31988247
Zammit NW, Siggs OM, Gray PE, Horikawa K, et al. (2019). Denisovan, modern human and mouse TNFAIP3 alleles tune A20 phosphorylation and immunity. Nat Immunol. 2019 Oct;20(10):1299-1310. doi: 10.1038/s41590-019-0492-0. Epub 2019 Sep 18. PMID: 31534238
Liu Z, Wang C, Yang J, Zhou B, Yang R, Ramachandran R, Abbott DW, Xiao TS (2019). Crystal Structures of the Full-Length Murine and Human Gasdermin D Reveal Mechanisms of Autoinhibition, Lipid Binding, and Oligomerization. Immunity. 2019 Jul 16;51(1):43-49.e4. doi: 10.1016/j.immuni.2019.04.017. Epub 2019 May 13. PMID: 31097341. PMCID: PMC6640092
Chirieleison, S.M., Rathkey, J.R. and D.W. Abbott*. (2018) Unique BIR domain sets dictate IAP-driven cell-death and NOD2 signal specificity. Sci Signal. 2018 Jul 17;11(539). pii: eaao3964. doi: 10.1126/scisignal.aao3964. *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. 2018 May 1;26(5):778-784.e3. doi: 10.1016/j.str.2018.03.002. Epub 2018 Mar 22.
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. Nat Cell Biol. 2018 Jan;20(1):58-68. doi: 10.1038/s41556-017-0003-1. Epub 2017 Dec 4.
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. J Biol Chem. 2018 Jan 19;293(3):1100-1105. doi: 10.1074/jbc.RA117.000408. Epub 2017 Dec 6. *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. J Biol Chem. 2017 Sep 1;292(35):14649-14658. doi: 10.1074/jbc.M117.797217. Epub 2017 Jul 18. *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. J Immunol. 2016 May 15;196(10):4291-7. doi: 10.4049/jimmunol.1502631. Epub 2016 Apr 4. *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. 2016 Jul 22;353(6297):399-403. doi: 10.1126/science.aae0477. Epub 2016 Jul 21.
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 Rep. 2015 Jul 28;12(4):537-44. doi: 10.1016/j.celrep.2015.06.050. Epub 2015 Jul 16. *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. 2014 Oct 24;289(43):29651-64. doi: 10.1074/jbc.M114.591388. Epub 2014 Sep 11. *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 Rep. 2013 Jul 25;4(2):352-61. doi: 10.1016/j.celrep.2013.06.036. Epub 2013 Jul 18. *corresponding author