Erik Anderson Korte

RESEARCH TOPICS

Primary research project topic and summarized version of the project

As a graduate student, I have worked under Dr. David Powell in the Autoimmune-Mediated Kidney Disease Center and developed a passion for intracellular signaling and protein-protein interaction as it relates to kidney disease, in particular a severe complication of systemic lupus erythematosus (SLE) known as Lupus Nephritis (LN).  My training under Dr. Powell at the University of Louisville has given me experience with a number of techniques and disciplines, including liquid chromatography-tandem mass spectrometry, cloning, cell and tissue culture, whole tissue analysis, secretome/cytokine characterization as well as common biochemical techniques including immunofluorescence, co-immunoprecipitation (Co-IP), real-time quantitative PCR (RT-qPCR), western blotting, and enzyme-linked immunosorbent assay (ELISA).  I have utilized these techniques to investigate the role of A20-binding Inhibitor of NF-κB (ABIN1), a ubiquitin-binding protein, in the development of SLE and specifically LN.  NF-κB is a crucial pathway in many cellular processes including cell survival and response to extracellular signals; uncontrolled NF-κB signaling has been linked to the development of a number of conditions including SLE and LN.  We have shown in vivo and in vitro that ABIN1 mutations in mice and humans lead immune hyperactivation and lupus-like renal disease while our human genetic screens have identified polymorphisms in the ABIN1 gene locus, named TNIP1, which confer increased risk for the development of LN in human patients (Korte et al., JASN, 2013).  A recurrent theme of my work is that target tissues exhibit characteristics which make them more susceptible to inflammatory damage, an idea supported by recent findings describing extremely low post-transplant recurrence rates for LN (Sprangers and Kupers, Transplant Rev. 2013).  We have shown that cultured cells of the kidney expressing an inactive form of ABIN1 produce and secrete higher levels of pro-inflammatory cytokines under both basal and stimulated conditions when compared to wild type as assessed by RT-qPCR, western blot, ELISA and mass spectrometry.  These secreted cytokines can be used to recruit primary neutrophils ex vivo across a synthetic membrane to mimic cytokinesis.  Our preliminary data support the hypothesis that loss of ABIN1 function has a direct role in “priming” the kidney for inflammatory damage and progression to LN through intracellular signaling aberrations, increased pro-inflammatory cytokine and chemokine secretion, and immune cell recruitment.  We have shown kidney-specificity for ABIN1 mutations, thus a better understanding of the ABIN1 signaling pathway in the kidney may produce kidney-specific pharmaceutical targets which reduce the risk of the development of LN without the systemic side effects of many current therapies.  Therefore future work will include Co-IP followed by mass spectrometry to identify ABIN1-interacting proteins in the kidney as well as an improved understanding of the mechanism of ABIN1-mediated protection from LN.

Thesis Committee

  1. Barbara Clark, Dept. of Biochemistry & Molecular Biology
  2. Michele M. Kosiewicz, Dept. of Microbiology & Immunology
  3. Dave Powell, Dept. of Nephrology
  4. Russ Prough, Dept. of Biochemistry & Molecular Biology
  5. Kenneth Ramos, Dept. of Biochemistry & Molecular Biology

Publications and Dissertations

  1. D. J. Caster* and E. A. Korte*, S. K. Nanda, K. R. McLeish, R. K. Oliver, R. T. G’sell, R. M. Sheehan, D. W. Freeman, S. C. Coventry, J. A. Kelly, J. M. Guthridge, J. A. James, K. L. Sivils, M. E. Alarcon-Riquelme, R. H. Scofield, I. Adrianto, P. M. Gaffney, A. M. Stevens, B. I. Freedman, C. D. Langefeld, B. P. Tsao, B. A. Pons-Estel, C. O. Jacob, D. L. Kamen, G. S. Gilkeson, E. E. Brown, G. S. Alarcon, J. C. Edberg, R. P. Kimberly, J. Martin, J. T. Merrill, J. B. Harley, K. M. Kaufman, J. D. Reveille, J.-M. Anaya, L. A. Criswell, L. M. Vila, M. Petri, R. Ramsey-Goldman, S.-C. Bae, S. A. Boackle, T. J. Vyse, T. B. Niewold, P. Cohen, and D. W. Powell, “ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis,” J. Am. Soc. Nephrol. JASN, Aug. 2013. *Equal Contributing First Authors
  2. E. A. Korte, Gaffney PM, Powell DW. (2011) Proteomic applications for defining cellular mechanisms and diagnostic markers of Systemic Lupus Erythematosus. Arthritis Research & Therapy 14, 204.
  3. Cummins TD, Mendenhall MD, Lowry MN, E. A. Korte, Barati MT, Khundmiri SJ, Salyer SA, Klein JB, Powell DW. (2011)  Elongin C Is A Mediator Of Notch4 Activity In Human Renal Tubule Cells. Biochim Biophys Acta. 1814,1748-1757.

     

    For Recent Publications, check PubMed Author Search

    Posters Presented

    National/International Conferences

    1. Korte, EA, G’Sell, RT; Sheehan, RM; Caster, DJ; Powell, DP.  Dysfunction of polyubiquitin binding by ABIN1 as a basis for lupus nephritis.  Abstract and Poster Presentation, Experimental Biology International Conference, San Diego, CA, April 2014.
    2. Caster DJ, Korte, EA, Birmingham DJ, Joglekar AS, Klein JB, Harley JB, Namjou B, McLeish KR, Merchant ML, Rovin, BH, and Powell, DW.Patterns of Circulating Autoantibodies in Patients with Lupus Nephritis. Abstract and Poster Presentation, American Society of Nephrology, Kidney Week, Atlanta, GA, November 2013.
    3. Korte, E.A., Cummins, T.D., Mendenhall, M.D., Barati, M.T., Klein, J.B., and Powell, D.W.  Elongin C is a Mediator of Notch4 Activity in Human Renal Tubule Cells.  Keystone Symposia, Whistler, Canada, 2012.
    4. Powell, D.W. Korte, E.A., Cohen, P., and Nanda, S.K. Disruption of ABIN1 inhibition of NF-κB activity causes lupus-associated glomerulonephritis. Keystone Symposia, Whistler, Canada, 2012.
    5. Caster DJ, Birmingham DJ, Klein JB, Harley JB, Korte EA, McLeish KR, Merchant ML, Rovin, BH, and Powell, DW. Identification of Candidate Target Antigens for Membranous Lupus Nephritis. American Society of Nephrology Kidney Week, San Diego, CA, November 2012.

    Local/Regional Conferences

    1. Korte, Erik; Sheehan, Ryan; Caster, Dawn; G’Sell, Rachel; Powell, David.  ABIN1 Dysfunction as a Basis for Lupus Nephritis. University of Louisville, Research! Louisville, 2013. Finalist, Poster Competition.
    2. Joglekar AS, Korte, EA, Caster DJ, Klein JB, Rovin BH, Harley JB, Merchant ML, McLeish KR, Stribinskis V, G’Sell RT, Sheehan RM, and Powell, DW.Target Antigens in Membranous Lupus Nephritis. Abstract and Poster Presentation, Research! Louisville, Louisville, KY, September 2013.
    3. Korte, Erik; Sheehan, Ryan; Caster, Dawn; G’Sell, Rachel; Powell, David.  ABIN1 Dysfunction as a Basis for Lupus Nephritis. University of Louisville, Biochemistry and Molecular Biology Research Colloquium, 2013.  1st Place Poster Graduate Student, 1st Place Poster Overall.
    4. Korte, E.A., Cummins, T.D., Mendenhall, M.D., Barati, M.T., Klein, J.B., and Powell, D.W.  Elongin C is a Mediator of Notch4 Activity in Human Renal Tubule Cells.  University of Louisville, Biochemistry and Molecular Biology Retreat, 2011.
    5. Caster DJ, Klein JB, Harley JB, Korte EA, McLeish KR, Merchant ML, Oliver R, Rovin BH, and Powell DW.Identification of GFRα1 as a Candidate Target Antigen in Membranous Lupus Nephritis.Research Louisville!, 2012, 1st place poster, clinical fellow

    Conferences Attended

    1. Experimental Biology, April 2014, San Diego, CA
    2. Kentucky Academy of Sciences, November 2013, Morehead State University
    3. NF-κB Signaling, Keystone Symposia, March 2012, Whistler, Canada

    Professional Memberships

    1. American Society of Nephrology
    2. American Association for the Advancement of Science
    3. American Society for Biochemistry and Molecular Biology
    4. Society for Experimental Biology and Medicine
    5. Kentucky Academy of Sciences