Associate Professorderek.email@example.com (216) 368-8564 (o) (216) 368-0494 (f)
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 continuued his clinical training in Anatomic Pathology at Brigham and Women's Hospital (Harvard Medical School) in Boston, MA. After completing his residency, 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 an Associate Professor with tenure. Current interests in the lab include the use of Next-Gen sequencing technologies to decipher inflammatory signaling pathways and the coupling of bioinformatics and proteomics to identify novel phosphorylation and ubiquitination sites. Outside of lab, he's quite busy keeping up with his wife, Dr. Kathryn Teng - the head of Personalized Health at the CCF and his two children, Annabelle (age 10) and Nate (age 7).
As humans, we are constantly exposed to disease-causing bacteria, fungi and viruses. Whether it is from a cough on a crowded airplane, a handshake from a business partner or the ingestion of undercooked chicken, our bodies are in a constant battle to recognize and combat bacteria and viruses. Not only do we have to activate our immune system to clear our bodies of these pathogens, we also have to deactivate our immune system after this initial activation. An overactive immune system can damage the body, leading to such autoimmune diseases as Rheumatoid Arthritis, Multiple Sclerosis and Crohn's Disease. Crohn's Disease is a devastating disease characterized by bloody diarrhea, severe abdominal pain and by an overall decrease in life-expectancy of approximately 15 years. Crohn's Disease arises from an inappropriate immune response to the bacteria normally present in the intestine. Normally, the intestine distinguishes normal from pathogenic bacteria, activating the immune system to eradicate pathogenic bacteria. After this eradication, the immune system must then be deactivated to prevent self-damage. In Crohn's Disease, the intestine responds inappropriately to the pathogenic bacteria. The initial immune response is too active, and the subsequent deactivation of this immune response is inadequate. The end result is an inflamed intestine producing severe pain and bloody diarrhea. While the intestinal bacteria play a role in the pathogenesis of Crohn's Disease, the patient's intestine also plays a role. The Crohn's Disease - susceptibility gene, NOD2, is an intestinal protein that is activated by these intestinal bacteria. Upon activation by these intestinal bacteria, NOD2 causes the release of a number of inflammatory mediators (cytokines) that help to establish an appropriate immune response. A large number of Crohn's Disease patients have a non-functional version of NOD2, and the activation of this faulty protein leads to an inability to tailor the intestinal immune response to bacteria. The end result is a viscous cycle of inflammation, ultimately resulting in Crohn's Disease. Our work centers both on the mechanism of activation of NOD2 and on the mechanism of cytokine release by NOD2. We are attempting to dissect the signaling pathways responsible for NOD2-induced Crohn's Disease, and we hope that this work leads to the identification of novel drug targets such that Crohn's Disease can be more effectively treated.
Shembade, N., Pujari, R., Harhaj, N.S., Abbott, D.W. and E.W. Harhaj. (2011) "The kinase IKKa inhibits activation of the transcription factor NF-kB by phosphorylating the regulatory molecule TAX1BP1" Nature Immunology, 12:834-43.
Liu, Y.C., Simmons, D.P., Li, X., Abbott, D.W., Boom, W.H. and C.V. Harding. (2012) "TLR2 signaling depletes IRAK1 and inhibits induction of type I IFN by TLR7/9. J Immunol. 288:1019-26.
Tigno-Aranjuez, J.T. and D.W. Abbott. (2012) "Ubiquitination and Phosphorylation in the Regulation of NOD2 signaling and NOD2-mediated Disease" Biochem and Biophys Acta. 1823:2022-8.
Marinis, J.M., Hutti, J.E., Homer, C., Cobb, B.A., Cantley, L.C., McDonald, C. and D.W. Abbott. (2012) "IKKα Phosphorylation of TRAF4 downregulates innate immune signaling." Molecular and Cellular Biology 32:2479-89.
Roget, K., Ben-Addi, A., Mambole-Dema, A., Gantke, T., Yang, H.T., Janzen, J., Morrice, N., Abbott, D. and S.C. Ley. (2012) IKK2 regulates TPL-2 activation of ERK-1/2 MAP kinases by direct phosphorylation of TPL-2 serine 400. Molecular and Cellular Biology. 32:4684-90.
Tigno-Aranjuez, J.T., Bai, X. and D.W. Abbott. (2013) "A discrete ubiquitin-mediated network regulates the strength of NOD2 signaling." Molecular and Cellular Biology. 33:146-158.
Jun, J.C., Cominelli, F and D.W. Abbott (2013) RIP2 activity in inflammatory disease and implications for novel therapeutics. Journal of Leukocyte Biology. In press (epub June 21, 2013; doi: 10.1189/jlb.0213109).
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.