MS/PhD: University of Illinois, Urbana-Champaign IL
Postdoctoral training: Massachusetts General Hospital / Harvard Medical School, Boston MA
Assistant Professor: Massachusetts General Hospital / Harvard Medical School, Boston MA
Research Scientist V: Wadsworth Center, NY Department of Health
Tick-borne diseases are a growing public health threat and pose a substantial burden on affected communities. Lyme disease is the most common vector-borne disease in the Northern Hemisphere and has now reached epidemic proportions in several locations in United States and Europe. The disease may present with a spectrum of clinical manifestations that involve different organ systems and can range in severity from mild acute infection to complications that persist after antibiotic therapy, termed post-treatment Lyme disease symptoms / syndrome. The reasons for this clinical heterogeneity are not well understood. Currently, there are no established diagnostic tests to identify patients at risk for adverse outcomes and treatment strategies for such patients are often not effective.
Our laboratory conducts translational research in human immunology with a focus on Lyme disease. Most signs and symptoms of Lyme disease are thought to be due to host-immune response to infection rather than the pathogen itself. Our work is centered on elucidating mechanisms that lead to protective or pathogenic immune responses and how such responses shape the clinical course and outcome of the disease in patients. In addition, we are determining how host and microbial (Borrelia burgdorferi) genetic factors modulate these responses during the infection and in the post-infectious period. For this purpose, we have developed a multi-faceted translational approach which combines targeted and discovery-based genomic and transcriptomic approaches to characterize clinical samples, 2) functional studies in cell culture models, and 3) correlations with well-defined clinical phenotype in patients. The goals of this work are to improve the understanding of disease pathogenesis, to develop novel diagnostic assays for early identification of patients at greater risk for severe disease, and to help guide more rational and effective treatment strategies for such patients. These studies involve collaborations with investigators across United States and Europe.
- Pathogenesis of Lyme disease and other tick-borne diseases
- Host immunity in protection from or susceptibility to infection and disease
- Infection-induced autoimmunity
- Host-pathogen interactions
- Impact of genetic variation on immune response to infection
- Biomarkers for adverse clinical outcomes
- Drug Discovery & Therapeutics
- Infection & Immunity
- Genes & Genomes
Current Major Activities
- Host immunity: Characterization of cellular and humoral immune responses in patients with Lyme disease and other tick-borne diseases to identify immune pathways associated with resolution or perpetuation of disease.
- Host genetics: Identification of host single-nucleotide polymorphisms in dysregulated immune responses and adverse clinical outcomes in Lyme disease.
- Microbial determinants of disease: Genomic analysis of B. burgdorferi isolates from patients to define microbial determinants of maladaptive immune responses and adverse clinical outcomes.
- Stromal cells as immune effectors: Evaluation of fibroblasts as unconventional immune cells that initiate and perpetuate immune responses during the infection and in the post-infectious period.
Sample of Recently Completed Studies
Lochhead RB, Strle K, Arvikar SL, Weis JJ, Steere AC. Lyme arthritis: linking infection, inflammation and autoimmunity. Nat Rev Rheumatology. 2021 Aug;17:449-461.
Strle K, Strle F. Post-treatment Symptoms in Lyme Borreliosis. Clin Infect Dis. 2020 Dec 15;71:3125-3127. PMCID: PMC7819510.
Lochhead RB, Ordoñez D, Arvikar SL, Aversa JM, Oh LS, Heyworth B, Sadreyev R, Steere AC, Strle K. Interferon-gamma production in Lyme arthritis synovial tissue promotes differentiation of fibroblast-like synoviocytes into immune effector cells. Cell Microbiol. 2019 Feb;21. PMCID: PMC6336510.
Strle K, Sulka KB, Pianta A, Crowley JT, Arvikar SL, Anselmo A, Sadreyev R, Steere AC. T-Helper 17 Cell Cytokine Responses in Lyme Disease Correlate With Borrelia burgdorferi Antibodies During Early Infection and With Autoantibodies Late in the Illness in Patients With Antibiotic-Refractory Lyme Arthritis. Clin Infect Dis. 2017 Apr 1;64.930-938. PMCID: PMC5850331.