Prof. Dr. Oliver A. Cornely & Dr. Philipp Köhler

1. Research Background:

In patients, a variety of risk factors predispose for different invasive fungal infections. With increasing cancer incidence in the elderly, the rate of intensive chemo- and immunotherapy increases, thus putting a larger number of patients at risk for invasive fungal infections. Patients with well-defined profound immunosuppression are at high risk for invasive aspergillosis and mucormycosis, whereas invasive candidiasis occurs in immunocompetent patients, too. Current standard diagnostics for invasive fungal infections such as blood culture, bronchoalveolar lavage, tissue biopsies and serological assays are sensitive to errors, sometimes unspecific, invasive and often contraindicated. The lack of reliable diagnostics along with high mortality lead to complex treatment strategies by means of prophylaxis, fever-driven, diagnosis-driven, and targeted treatment approaches. Furthermore, the duration of finding the right diagnosis often delays the initiation of directed therapy, thus delaying the cancer therapy.

2. Research questions addresses by the group:

The aim of the laboratory is the development of novel diagnostic approaches for invasive fungal infections. To achieve this goal, we have set up a FungiResearch network (http://fungiresearch.uni-koeln.de) and act as the lab of the European Excellence Center of Medical Mycology (https://www.ecmm.info). With the development of the antigen-reactive T cell assay a non-invasive diagnostic allows fast and valid identification of pathogens to genus and species level when standard tests remain negative or patients’ comorbidities forbid invasive diagnostics. We use peripheral blood mononuclear cells (PBMCs) from patients’ full blood and challenge them with fungal lysates. If the PBMCs encounter a repetitive fungal challenge, we identify fungus-reactive CD4+ T cells in the patient’s blood via flow cytometry.1-3

The current project, which was supported by a clinical GEROK position by the CECAD, is advanced to further bacterial and fungal pathogens for clinical diagnostics and to investigate the cellular immune response.1,2 With the development of new diagnostic tools, in cooperation with the AG Zuccaro (Functional genomics and molecular biology of symbiotic fungi; Botanical Institute, University of Cologne), we want to overcome the problem of false negative standard diagnostics to facilitate targeted treatment and thus improve patient outcome.

3. Possible projects:

Possible projects for PhD students will focus on the development of new diagnostic tests to allow diagnosis of invasive fungal infections without the need for invasive procedures (e.g. lung or liver biopsies):

  • Progression of the antigen-reactive T cell stimulation assays to various fungal pathogens – investigation of lysate stimulation and upregulation of CD154 and CD69 in samples of patients with invasive fungal infections.
  • Development of new screening tests in cooperation with the AG Zuccharo (Functional genomics and molecular biology of symbiotic fungi, Botanical Institute, University of Cologne).

4. Applied Methods and model organisms:

We employ a wide range of methods and techniques depending on the research based-question with freshly drawn patient samples including:

  • Cell Culture
  • Stimulation Assays
  • Flow Cytometry
  • Fluorescence Microscopy (in Cooperation with the CECAD Imaging Facility Head: A. Schauss)

5. Desirable skills and qualifications:

We seek highly motivated students with a strong interest in Infectious Diseases research. Desired qualities are previous experience or interest in the use cell culture, flow cytometry and fluorescence microscopy techniques, fluent English, a strong aptitude for teamwork and previous experience or interest in statistical analysis.

6. References

  1. Koehler FC, Cornely OA, Wisplinghoff H, et al. Candida-Reactive T Cells for the Diagnosis of Invasive Candida Infection-A Prospective Pilot Study. Front Microbiol 2018;9:1381.
  2. Koehler FC, Cornely OA, Wisplinghoff H, Chang DH, Richter A, Koehler P. Candida reactive T cells for the diagnosis of invasive Candida infection of the lumbar vertebral spine. Mycoses 2017.
  3. Bacher P, Steinbach A, Kniemeyer O, et al. Fungus-specific CD4(+) T cells for rapid identification of invasive pulmonary mold infection. American journal of respiratory and critical care medicine 2015;191:348-52.