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Start / Research / Research Reports / Research report 2020 / Institutes / FB_Legal Medicine

In 2020, the work of the institute was predominantly characterized by challenges due to the pandemic caused by the novel coronavirus SARS-CoV-2. We have commenced to autopsy corpses infected with SARS-CoV-2 as early as spring 2020 with the purpose to enlarge the still small data base on patho-morphological and molecular-genetic specifics of this new disease by providing novel scientific insights. During the reporting period, the Section Pathology has consolidated research infrastructur and staff as well as focussed and developed research fields. For state of the art in situ investigation of cell-cell interactions in various human pathologies (spatial phenotyping), a highest-performance multiplex immunofluorescence slide scanner was purchased.

Contact

Prof. Dr. Gita Mall
Am Klinikum 1
07747 Jena

Pathology:
Prof. Dr. Nikolaus Gaßler

Institute of Legal Medicine and Section Pathology

Electron microscope image (subsequently colored) of the blood-air transition in the alveoli of a patient who died of COVID-19. Due to the virus-related dying of the lung epithelial cells, the surface-active surfactant is missing in the blue striped area.
Electron microscope image (subsequently colored) of the blood-air transition in the alveoli of a patient who died of COVID-19. Due to the virus-related dying of the lung epithelial cells, the surface-active surfactant is missing in the blue striped area.

Research projects

Studies on COVID-19 deceased in the early post-mortem interval

Principal investigator: Prof. Dr. Gita Mall
Carl-Zeiß-Stiftung 2020

Comprehension of novel diseases such as COVID-19 can be improved by performing prompt autopsies and subsequent scientific processing of samples obtained during autopsy. In the current study, deceased individuals who were proven to be infected with SARS-CoV-2, are autopsied according to current scientific standards, provided a declaration of consent is present. Cause of death and comorbidities are determined and comprehensive sampling of organs and tissues conducted.

Temperature based death time estimation

Principal investigator: Prof. Dr. Gita Mall
DFG 2020 - 2023

Projektleiterin: Prof. Dr. Britta Qualmann
DFG 2020-2020

A DFG project was started in cooperation with the Zuse Institute Berlin in 2021 after comprehensive preliminary work. Sensitivity analyses considering the cooling conditions (e.g. ambient temperature) and Finite Element parameters (e.g. mesh density) of a CT-based FE human model. Experimental measurements and numerical simulations are work in progress aiming mapping complex cooling scenarios at (e.g. covering and clothing).

Age diagnostics on subdural indicators of the shaken baby syndrome

Principal investigator: PD Dr. Daniel Wittschieber
DFG 2010 - 2021

The shaken baby syndrome (SBS) is a very severe variant of physical child abuse. The current multi-center project, which is coordinated from Jena, addresses several questions of age estimation in traumatic subdural fluid collections, which are an essential feature of SBS. Using comprehensive case data from medico-legal institutes and public prosecution offices, the study aims to provide more precise statements on the time of crime, thereby narrowing the circle of suspects.

Determination of PETN and its metabolites in serum

Principal investigators: Dr. Daniela Wissenbach, PD Dr. Frank T. Peters
2017 - 2021

Aim of the collaborative project with „Klinik für Gebursmedizin, UKJ“, is the quantitative assessment of pentaeritrithyltetranitrate (PETN) and its metabolites in human serum. At the beginning of the reporting period, a corresponding LC-MS method was developed. Currently, the method is being validated. The project is part of the clinical study „Pentaeritrithyltetranitrat (PETN) zur Sekundärprophylaxe der intrauterinen Wachstumsretardierung“.

In vitro diffusion experiments for determination of drug transferability using Dura Mater tissue

Principal investigatoras: Dr. Dirk K. Wissenbach, PD Dr. Frank T. Peters
2020 - 2021

In cooperation with the Spine Department at Waldklinikum Eisenberg, the in vitro diffusion of selected drugs (e.g. antibiotics, anesthetics and antifibrinolytics) through Dura Mater tissue is analyzed using a two compartment in vitro design. For both compartments (donor and acceptor) the concentration of the drugs are determined by LC-MS.

Investigating tumor biological role of ACSL5 in non-small cell lung cancer

Relevance for tumorigenesis, diagnosis and therapeutics

Principal investigator: Dr. Yunxia Ma
IZKF (MSP) 2020 - 2023

Reprogramming of lipid metabolism through regulation of acyl-coA synthetase long chain 5 (ACSL5) metabolites is associated with cancer. ACSL isoenzymes have different effects on driver mutant non-small cell lung cancer (NSCLC). ACSL3 and ACSL4 play an oncogenic role in the maintenance of mutant lung cancer, however, little is known about the function of the mitochondrial ACSL5. We showed that ACSL5 is expressed in EGFR mutant cell lines and had a potential diagnostic value in lung adenocarcinoma. The project is aimed

  1. to define the tumor biological role of ACSL5 in NSCLC as well as its relation to EGFR mutation during tumor development,
  2. to determine the effect of ACSL inhibitors in combination with therapeutic drugs by using 3D patient derived tumor organoids, and
  3. to evaluate the clinical relevance of the interaction of ACSL5 expression, methylation status and driver mutations.

 

Establishment of a multiplex immunfluorescence technology platform for in situ detection of cell cell interaction by spatial phenotyping in human pathologies

Example of a 4-color Multiplex Immunefluorescence staining of the invasion front of an colon carcinoma: red = cytokeratin, green = E-cadherin, blue = ß-catenin, white = nuclei
Example of a 4-color Multiplex Immunefluorescence staining of the invasion front of an colon carcinoma: red = cytokeratin, green = E-cadherin, blue = ß-catenin, white = nuclei

Principal investigator: Prof. Dr. Nikolaus Gaßler

Freistaat Thüringen 2020 - 2021

In pathology, diagnostically relevant marker sets will perspectively be detected by so-called multiplex staining methods. Here, up to 10 target structures can be simultaneously coloured. Beside protein detection itself, also the spatial distribution of cell types can be defined (spatial phenotyping). Aim of the project is the implementation of the complex staining and analysis methods in research. Currently, validation on selected test samples compared to conventional immune staining methods is running.

Investigating the role of different ACSL5 splice-isoforms in colon cancerogenesis

Principal investigators: Prof. Dr. Nikolaus Gaßler, Miljana Nenkov

Alteration in fatty acid metabolism is involved in cancer pathogenesis. Fatty acid level was reported as a prognostic marker also in colorectal carcinoma (CRC). Acyl-CoA synthetases (ACSLs) are essential in activating fatty acids for further metabolic processes. Impaired expression of ACSL5 is associated with sporadic colorectal adenocarcinomas. We could show a significant correlation between p53 and ACSL5 in primary CRC samples and an influence of TP53 on ACSL5 expression in vitro (HCT116 and HCT116 p53-/- cells). Aims are

  1. investigating the role of different ACSL5 isoforms (a, b, x1) in colorectal carcinogenesis with focus on p53 - ACSL5 interplay,
  2. unraveling the networking between p53 and ACSL5 and
  3. exploring a potential therapeutic use in colon cancer.

Selected publications

Outstanding achievements

The institute hosted the 2nd and 3rd Expert Exchange of the association of toxicological and forensic chemistry in February 2019 and 2020.