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.

Publications Visit PubMed for a full listing of Hans-Guido Wendel's publications. Go »

The main areas of research in the lab are:

  1. The pathogenesis and treatment of lymphoid malignancies. Figure 1 Figure 1 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).

  1. The control of oncogene translation in cancer. Figure 2 Figure 2 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.


Wolfe AL, Singh K, Zhong Y, Drewe P, Rajasekhar VK, Sanghvi VR, Mavrakis KJ, Jiang M, Roderick JE, Van der Meulen J, Schatz JH, Rodrigo CM, Zhao C, Rondou P, de Stanchina E, Teruya-Feldstein J, Kelliher MA, Speleman F, Porco JA, Pelletier J, Rätsch G, Wendel HG.Nature. 2014 Jul 27. doi: 10.1038/nature13485. (Epub ahead of print)[PMID: 25079319]

Oricchio E, Nanjangud G, Wolfe AL, Schatz JH, Mavrakis KJ, Jiang M, Liu X, Bruno J, Heguy A, Olshen AB, Socci ND, Teruya-Feldstein J, Weis-Garcia F, Tam W, Shaknovich R, Melnick A, Himanen JP, Chaganti RS, Wendel HG. The Eph-receptor A7 is a soluble tumor suppressor for follicular lymphoma. Cell. 2011 Oct 28;147(3):554-64. doi: 10.1016/j.cell.2011.09.035.

Schatz JH, Oricchio E, Wolfe AL, Jiang M, Linkov I, Maragulia J, Shi W, Zhang Z, Rajasekhar VK, Pagano NC, Porco JA Jr, Teruya-Feldstein J, Rosen N, Zelenetz AD, Pelletier J, Wendel HG. Targeting cap-dependent translation blocks converging survival signals by AKT and PIM kinases in lymphoma. J Exp Med. 2011 Aug 29;208(9):1799-807. doi: 10.1084/jem.20110846. Epub 2011 Aug 22.

Mavrakis KJ, Van Der Meulen J, Wolfe AL, Liu X, Mets E, Taghon T, Khan AA, Setty M, Rondou P, Vandenberghe P, Delabesse E, Benoit Y, Socci NB, Leslie CS, Van Vlierberghe P, Speleman F, Wendel HG. A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL). Nat Genet. 2011 Jun 5;43(7):673-8. doi: 10.1038/ng.858.

Mavrakis KJ, Wolfe AL, Oricchio E, Palomero T, de Keersmaecker K, McJunkin K, Zuber J, James T, Khan AA, Leslie CS, Parker JS, Paddison PJ, Tam W, Ferrando A, Wendel HG. Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia. Nat Cell Biol. 2010 Apr;12(4):372-9. doi: 10.1038/ncb2037. Epub 2010 Feb 28.

Wendel HG, De Stanchina E, Fridman JS, Malina A, Ray S, Kogan S, Cordon-Cardo C, Pelletier J, Lowe SW. Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature. 2004 Mar 18;428(6980):332-7.

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Selected Achievements

Identification of an eIF4A dependent mechanism that controls the production of key onocproteins including c-MYC (2014).

Development of a rational combination therapy for high-risk follicular lymphoma (2014).

Generation of a cell engineering strategy to enhance the safe use of stem cells for therapy (2014).

Member, American Society for Clinical Investigation (2013)

Identification and therapeutic delivery of the soluble tumor suppressor EphA7 in lymphoma

Development of genetically and pathologically accurate model of follicular lymphoma

Definition of network of onogenic microRNAs in T cell leukemia

Development of genetic screen to define key targets of onocgenic microRNAs in T cell leukemia

Identification of the onocgenic property of the eIF4E translation factor

Identification of eIF4E phosphorylation as a therapeutic target in cancer