Education and Training
Daniel Kazdal graduated in Biology, after conducting studies at the Johannes Gutenberg-University Mainz and at the University of Vienna. In 2015 he finished his PhD studies in Forensic Molecular Biology at the Institute of Legal Medicine Mainz and started his postdoc at the Institute of Pathology Heidelberg, where he focused his research on the intratumoral heterogeneity of pulmonary adenocarcinoma and on molecular alterations in consideration of translational thoracic pathology. Since 2018 he is also part of the Center for Molecular Pathology at Institute of Pathology Heidelberg where he contributes to molecular diagnostics besides his research.
Expertise
His area of activity within the Center for Molecular Pathology, including the analysis of DNA and RNA based next generation (NGS) profiles as well as the participation in molecular tumor boards, granted him a profound expertise in the field of molecular diagnostic, especially regarding non-small cell lung cancer.
He has already published several studies from his ongoing research project regarding the spatial distribution and variability of morphological and molecular markers (including NGS: driver mutation, mitochondrial mutations tumor mutational burden; 450k: epigenetic profiling; NanoString: gene expression profiling, digital Pathology: immunohistochemical analysis). Correlation with clinical data enables the identification of molecular parameters that could be of prognostic or predictive relevance. Further, this multiregional analysis can help to assess the reliability of known diagnostic biomarker by determining the variability between a single sample based analysis to the comprehensive situation in a tumor.
- Intratumoral heterogeneity (ITH) in lung adenocarcinoma
- Identification and evaluation of biomarkers suitable for molecular pathological diagnostics
- Translational thoracic pathology
Lung Cancer (LC)
1. Ball M, Romanovsky E, Schnecko F, Kirchner M, Neumann O, Brandt R, Beck S, Seker-Cin H, Kluck K, Ourailidis I, Goldschmid H, Fink A, Volckmar AL, Menzel M, Allgäuer M, Schirmacher P, Budczies J, Stenzinger A, Kazdal D. Clinical Implementation of a High-Throughput Automated Comprehensive Genomic Profiling Test: TruSight Oncology 500 HT. J Mol Diagn. 2025 Feb;27(2):154-162. doi: 10.1016/j.jmoldx.2024.11.005. Epub 2024 Dec 12. PMID: 39674366; PMCID: PMC12179514.
2. Budczies J, Kazdal D, Menzel M, Beck S, Kluck K, Altbürger C, Schwab C, Allgäuer M, Ahadova A, Kloor M, Schirmacher P, Peters S, Krämer A, Christopoulos P, Stenzinger A. Tumour mutational burden: clinical utility, challenges and emerging improvements. Nat Rev Clin Oncol. 2024 Oct;21(10):725-742. doi: 10.1038/s41571-024-00932-9. Epub 2024 Aug 27. PMID: 39192001.
3. Menzel M, Ossowski S, Kral S, Metzger P, Horak P, Marienfeld R, Boerries M, Wolter S, Ball M, Neumann O, Armeanu-Ebinger S, Schroeder C, Matysiak U, Goldschmid H, Schipperges V, Fürstberger A, Allgäuer M, Eberhardt T, Niewöhner J, Blaumeiser A, Ploeger C, Haack TB, Tay TKY, Kelemen O, Pauli T, Kirchner M, Kluck K, Ott A, Renner M, Admard J, Gschwind A, Lassmann S, Kestler H, Fend F, Illert AL, Werner M, Möller P, Seufferlein TTW, Malek N, Schirmacher P, Fröhling S, Kazdal D, Budczies J, Stenzinger A. Multicentric pilot study to standardize clinical whole exome sequencing (WES) for cancer patients. NPJ Precis Oncol. 2023 Oct 20;7(1):106. doi: 10.1038/s41698-023-00457-x. PMID: 37864096; PMCID: PMC10589320.
4. Neumann O, Burn TC, Allgäuer M, Ball M, Kirchner M, Albrecht T, Volckmar AL, Beck S, Endris V, Goldschmid H, Lehmann U, Seker-Cin H, Uhrig S, Roessler S, Budczies J, Fröhling S, Longerich T, Wagner AH, Vogel A, Schirmacher P, Stenzinger A, Kazdal D. Genomic architecture of FGFR2 fusions in cholangiocarcinoma and its implication for molecular testing. Br J Cancer. 2022 Nov;127(8):1540-1549. doi: 10.1038/s41416-022-01908-1. Epub 2022 Jul 23. PMID: 35871236; PMCID: PMC9553883.
5. Kazdal D, Endris V, Allgauer M, Kriegsmann M, Leichsenring J, Volckmar AL, Harms A, Kirchner M, Kriegsmann K, Neumann O, Brandt R, Talla SB, Rempel E, Ploeger C, von Winterfeld M, Christopoulos P, Merino DM, Stewart M, Allen J, Bischoff H, Meister M, Muley T, Herth F, Penzel R, Warth A, Winter H, Frohling S, Peters S, Swanton C, Thomas M, Schirmacher P, Budczies J, Stenzinger A. Spatial and temporal heterogeneity of panel-based tumor mutational burden (TMB) in pulmonary adenocarcinoma: separating biology from technical artifacts.J Thorac Oncol. 2019.
Lung Research - Projects
1. Intratumoral heterogeneity of immuno-oncological factors
Gene expression profiling is a promising approach for the prediction of response to immune checkpoint blockade, as it allows the concurrent determination of different immuno-oncological aspects. In this project we plan to investigate the inter- and intratumoral heterogeneity of specific gene signatures associated with the immune response and the interplay of tumor and immune cells. In this consideration the gene expression level of 770 specific genes should be determined in a multiregional analysis and tested for correlation with histological and genetic data.
2. Genetic Alterations of Mitochondria
In preceding studies, we could show that somatic mutations of the mitochondrial genome (mtDNA) are either ubiquitously present in all tumor segments or spatially restricted to specific regions. The same ubiquitous mutations were also detectable in relapse samples of matched primary lesions. Aim of this project is to evaluate the potential value of mtDNA sequencing of the primary tumor and consecutive analysis of plasma samples, regarding clinical monitoring and the early detection of a relapse.
3. Digital Pathology
The exact determination of the tumor cell content (the tumor purity) of a sample is crucial for many molecular approaches, in order to provide reliable results and to prevent misinterpretation, especially regarding clinical molecular diagnostics. By now there are several computer aided tools (digital pathology) available to support the evaluation of immuno-/ histological images. In this regard we want to determine the concordance between a digital semi-automatic and the conventional determination of the tumor cell content, using both H&E stained sections and TTF1-immunohistochemical stainings from lung adenocarcinoma specimen representing different histological growth patterns. It is planned to compare the results using two different software approaches with the conventional evaluation of a broad set of participants displaying different level of pathological expertise.
