As a physician-scientist in the Ludwig Center for Cancer Genetics and Therapeutics & Howard Hughes Medical Institute at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Dr. Konig’s research focuses on developing novel chimeric T cell- and antibody-based strategies for the treatment of rheumatic diseases and cancer. A primary goal of his translational research program is the development of antigen-specific and personalized immunotherapies for various autoimmune rheumatic diseases, with the intent to achieve sustained disease remission and functional cure.
Dr. Konig has a long-standing interest in mechanisms of disease initiation and propagation in autoimmune rheumatic and inflammatory disease. His postdoctoral research in the Division of Rheumatology elucidated how specific bacteria may cause loss of immunological tolerance and the development of anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis, a hallmark of this autoimmune disease. His work identified Aggregatibacter actinomycetemcomitans as a pathogen that induces hypercitrullination and the release of citrullinated autoantigens from neutrophils during periodontal infection. These mechanistic findings may explain the clinical association of rheumatoid arthritis and gum disease and prove critical to research efforts to prevent the development of rheumatoid arthritis in high-risk individuals with evidence of preclinical autoimmunity.
Lab Website: Konig Lab
Technology Expertise Keywords
antigen-specific immunotherapy; T cell engineering; chimeric antigen receptor T-cell therapy; bispecific antibodies; protein citrullination
Clinical Trial Keywords
alpha-1 adrenergic receptor antagonists; doxazosin; prazosin; COVID-19-associated hyperinflammation
Dr. Konig is engaged in research studies and clinical trials to investigate whether alpha-1 adrenergic receptor antagonists (e.g., doxazosin, prazosin) can prevent mortality in COVID-19 by disrupting the catecholamine-cytokine feed-forward loop that has been shown to drive dysregulated immune responses in animal models.
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Paul S, Pearlman AH, Douglass J, Mog BJ, Hsiue EH, Hwang MS, DiNapoli SR, Konig MF, Brown PA, Wright KM, Sur S, Gabelli SB, Li Y, Ghiaur G, Pardoll DM, Papadopoulos N, Bettegowda C, Kinzler KW, Zhou S, Vogelstein B. TCR β chain-directed bispecific antibodies for the treatment of T cell cancers. Sci Transl Med. 2021 Mar 10;13(584):eabd3595. doi: 10.1126/scitranslmed.abd3595. Epub 2021 Mar 1. PMID: 33649188
Hsiue EH, Wright KM, Douglass J, Hwang MS, Mog BJ, Pearlman AH, Paul S, DiNapoli SR, Konig MF, Wang Q, Schaefer A, Miller MS, Skora AD, Azurmendi PA, Murphy MB, Liu Q, Watson E, Li Y, Pardoll DM, Bettegowda C, Papadopoulos N, Kinzler KW, Vogelstein B, Gabelli SB, Zhou S. Targeting a neoantigen derived from a common TP53 mutation. Science. 2021 Mar 5;371(6533):eabc8697. doi: 10.1126/science.abc8697. Epub 2021 Mar 1. PMID: 33649166; PMCID: PMC8208645
Giles JT, Reinholdt J, Andrade F, Konig MF. Associations of Antibodies Targeting Periodontal Pathogens With Subclinical Coronary, Carotid, and Peripheral Arterial Atherosclerosis in Rheumatoid Arthritis. Arthritis Rheumatol. 2021 Apr;73(4):568-575. doi: 10.1002/art.41572. Epub 2021 Mar 3. PMID: 33205531; PMCID: PMC8005413
Konig MF, Powell M, Staedtke V, Bai RY, Thomas DL, Fischer N, Huq S, Khalafallah AM, Koenecke A, Xiong R, Mensh B, Papadopoulos N, Kinzler KW, Vogelstein B, Vogelstein JT, Athey S, Zhou S, Bettegowda C. Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists. J Clin Invest. 2020 Jul 1;130(7):3345-3347. doi: 10.1172/JCI139642. PMID: 32352407; PMCID: PMC7324164
Konig MF, Abusleme L, Reinholdt J, Palmer RJ, Teles RP, Sampson K, Rosen A, Nigrovic PA, Sokolove J, Giles JT, Moutsopoulos NM, Andrade F. Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Sci Transl Med. 2016 Dec 14;8(369):369ra176. doi: 10.1126/scitranslmed.aaj1921. PMID: 27974664; PMCID: PMC5384717