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Allgemeine Pathologie
Pathologie

AG Lasitschka


Overview:


Mucosal Immunology


Tumors of the Lung and Pleura


Core Facilities:

Center for Model System and Comparative Pathology (CMCP)
Laser capture microdissection
Tissue bank for inflammatory diseases Heidelberg (GEZEH)
Biobank of the German Centre for Infectious Diseases (DZIF)

Group members:

Dr. med. Felix Lasitschka
Dr. med. univ. Cornelia Thöni
Ewgenija Gutjahr
Alexander Harms
Dr. rer. nat. Daniel Kazdal
Jutta Scheuerer

Publications:
Pubmed

Mucosal Immunology

The intestinal mucosa, as the largest body surface to interface with the external environment, is continuously exposed to a large amount of commensal bacteria and nutritional foreign antigens. In spite of this massive antigen exposure usually no local symptomatic or adaptive systemic immune responses occur. This “tolerogen” state requires a complex regulation of luminal factors, intestinal epithelial cells and cellular components of the mucosa-associated immune system by the intestinal milieu. Disturbances of the intestinal milieu lead to unphysiological immune responses that cause inflammatory bowel disease (IBD), namely ulcerative colitis and Crohn’s disease, and as a last consequence cancer. Our aim is to identify distinct properties of different intestinal cell populations, e.g. epithelial cells, T-cells, macrophages, that contribute to this “tolerogenic” state. Therefore we employ an innovative spectrum of experimental methods, e.g. laser capture microdissection, microarray-analysis, quantitative PCR, in situ hybridisation, western blotting, immunohistology and cell culture techniques to characterise the micromilieu of
the gut and to identify molecular factors, that cause a deregulation of the immune homeostasis in IBD and eventually lead to inflammation induced tumorigenesis.


Research projects

  • Redoxregulation as a risk factor in inflammation induced carcinogenesis.

The individual prognosis of malignancy in patients with ulcerative colitis or Crohn's disease has only been estimated in a very limited sense. Therefore, the establishment of reliable and easily identifiable predictive tumor markers in practice is an urgent task of gastroenterological pathology. There is evidence from animal models that tissue associated inflammatory mediators have a significant impact on the development and progression of these tumors. Using compartment specific molecular expression analysis, mechanisms of chronic inflammation and inflammation induced tumorigenesis will be identified and correlated with already existing gene expression data of inflammatory bowel disease.

  • Pathogenesis of Pouchitis


Pouchitis, defined as the inflammation of the ileum mucosa in the pouch, is one of the major complications after restorative proctocolectomy and Ileoanal Pouchimplantation (IAP) in ulcerative colitis (UC) patients. The severity of symptoms varies and quality of patient’s life are impaired. There are indications that the pathogenic mechanisms of the underlying disease, i.e. ulcerative colitis are associated with a disturbed response to bacterial antigens in the pathogenesis of pouchitis. An important mechanism in this case represents a failure in the intestinal barrier, which is
formed by antimicrobial peptides, the mucus itself, tight and adherent junctions between the intestinal epithelial cells and the mucosal immune system. Severe pouchitis in patients with ulcerative colitis shows a significant dysregulation of various adherent junction proteins compared to the pouch samples of FAP patients. Pouchitis in ulcerative colitis patients is characterized by a dysregulation of adherent junction proteins compared to FAP patients and may contribute to a fundamental difference between the two disease entities.

  • Tumors of the Lung and Pleura


Translational research integrates knowledge of different scientific fields (e.g. basic research or population studies) to focus on patient oriented issues, in order to make latest therapeutic methods applicable in the clinical practice. Against this background our research is directed towards the study of lung cancer, the most frequent tumor related cause of death worldwide.
Traditionally, tumors of the lung are divided into the two groups:  small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Approximately 85% of these tumors belong to the NSCLC, which comprises numerous entities including adenocarcinoma (ADC; 60%), squamous cell carcinoma (SQCC; 30%), adeno-squamous carcinomas, or large cell carcinomas. Besides NSCLC and SCLC, typical and atypical carcinoids, and large cell neuroendocrine carcinomas are of relevance in daily routine practice. Furthermore, tumors of the pleura, predominantly mesothelioma, and solitary fibrous tumors need to be considered.Today, morphological, histochemical, immunohistochemical, and molecular pathological analyses allow precise diagnoses and tumor subtyping, but also predictive analyses of a steadily growing number of biomarkers. Molecular alterations like activating EGFR mutations or ALK translocations are nowadays the basis for oncologists to select appropriate therapies for the individual patient.


Research projects

  • Dynamics of Morphological and Molecular Evolution of Pulmonary Adenocarcinoma


In the last couple of years extensive morphological and molecular-pathological studies have identified several new prognostically and therapeutically relevant parameters regarding pulmonary ADC’s, that have led to a significant improvement in the survival of patients. New morphological classifications based on the growth pattern of a tumor, which can be associated with molecular alterations, give considerably better prognostic assessments. In the next step those parameters should be investigated consistently and integrated during regularly tumor progression as well as during radio-/chemo therapy. The resulting findings have great potential to broaden the comprehension of tumor biology and could improve the prognostic stratification along with associated therapeutically options. During tumor progression the growth patterns show sequential changes. This allows a systematic analysis of morphological and molecular characteristics (mutations, amplifications, mtDNA, miRNA, and methylation) in different stages of tumor evolution.

 



  • Heterogeneity of Tissue-derived Biomarkers in Pulmonary Adenocarcinoma


The majority of pulmonary ADCs (> 80%) bears more than one growth pattern, that is to say, they are morphological heterogeneous. Evidently those observations are the result of different stages in tumor progression. In addition to the question of which genetic and epigenetic elements are influencing the development of a tumor, it is especially interesting to learn what kind of diagnostic and therapeutic relevance could be associated with the distribution of a certain alteration. The treatement of spatially heterogeneous occurring driver mutations or resistance factors, which are the main cause for tumor recurrence and progression under therapy, require new multimodal approaches in order to set up an enhanced and individualized therapy for those patients

 

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