The focus of research in my lab is on the genetics of cancer and the development of new therapies. We want to understand how genetic lesions incurred during tumor evolution impact responses to conventional therapy and if they provide opportunities for new therapies.
Visit PubMed for a full listing of Hans-Guido Wendel's publications.
The main areas of research in the lab are:
- The pathogenesis and treatment of lymphoid malignancies.
We use genetic approaches including genomic analyses, genetic screens, and advanced murine models to explore the functional consequences of genetic aberrations in human leukemia/lymphoma. The goal is to gain actionable insight and uncover new therapeutic opportunities.
Figure 1) Functional genomics study to identify new therapeutic targets in follicular lymphoma. We performed a genetic screen to pinpoint relevant tumor suppressors within a large chromosomal deletion and developed an antibody-conjugate to deliver a soluble tumor suppressor (EPHA7) to cancer cells in situ (Oricchio et al Cell, 2011).
- The control of oncogene translation in cancer.
We found that key translation initiation factors can drive cancer development in vivo. Exciting new data indicate that selective mechanisms control the translation of key growth genes, transcription factors, and oncogenes. This implies a new level of translational selectivity and the potential to block oncogene production by targeting enzymes required for their translation.
Figure 2) Selective and targetable mechanisms of translational control. Specific sequence and structural elements in a transcripts 5’UTR encode a requirement for co-factors. For example, several oncogenes harbor conserved RNA G-quadruplex structures in their 5’UTRs. These require the eIF4A RNA helicase activity for and inhibitors like Silvestrol can block their translation.