Researcher Database
Prof. Dr. Jan-Henning Klusmann
Department of Pediatrics
Theodor-Stern-Kai 7
60590 Frankfurt am Main
Program
Exploitation of Oncogenic Mechanisms (EOM)
Summary
The research group at the Department of Pediatric Hematology and Oncology, Goethe University Frankfurt has been focusing on molecular and translational studies on acute myeloid leukemia especially in infants. Using one of the largest collection of pediatric AML specimen worldwide within the AML-BFM study group, they combine state-of-the-art omics profiling (including whole genome sequencing, global mRNA and ncRNA expression profiling) with functional analyses and disease modeling in primary human cells.
This allowed to identify several non-coding RNAs as central regulators of hematopoiesis and leukemogenesis. By applying genome editing, they elucidate the molecular processes induced by numerous known mutations that his research group and others identified in leukemia genomes. This has enabled new understanding of leukemic transformation in children with Down syndrome and chromosomal rearrangements in pediatric leukemia. Beyond genetic mutations, they mapped transcriptional landscapes of leukemia and normal hematopoiesis, providing further insights into the cellular networks hijacked by this disease. These insights guide hypothesis-driven genetic and pharmacologic testing of therapeutic vulnerabilities in patient-derived xenografts.
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DKTK Junior Group Leader for Cancer Systems Biology
Single-cell approaches have not only revealed a wide variety of cell states, characterized by cells exhibiting striking differences in their transcriptional profile, but have also illuminated the mechanisms underlying state transitions in health and disease. Cellular plasticity and adaptive state changes have recently emerged as a basis for therapeutic resistance in cancer, and a better understanding of how cell state transitions are regulated is critical to develop therapeutic approaches that can overcome therapy resistance.
Our research focuses on understanding the mechanisms driving non-genetic cellular heterogeneity and therapy resistance in malignancy. Using novel single-cell sequencing approaches, we seek to develop new experimental and computational strategies to define altered cell states in both, cancer and immune cells. Our aim is to leverage a data driven strategy combined with single cell genomics and systems biology to address the challenges posed by heterogeneity in cancer, and to develop new strategies to overcome it, with the aim of translating laboratory-based findings into the clinic.