The Danilov lab focuses on early drug development in lymphoid malignancies, with a goal of ushering novel therapeutic approaches into clinic. The team follows the "bench to bedside to bench" paradigm, where pre-clinical findings in the laboratory lead to initiation of early phase clinical trials in lymphoma. Subsequently, correlative studies advance understanding of cancer biology and drug pharmacodynamics, spurring progress in the field of molecular therapeutics.
The Danilov lab focuses its attention on drug resistance in lymphoma, with emphasis on key signaling pathways (TNF receptor and NFκB signaling). Using stromal co-cultures, the Danilov lab models the tumor-supportive microenvironment in vitro as well as studies drug resistant tumors in vivo. The lab has a track record investigating the function of the ubiquitin-proteasome system in cancer, and has studied proximal components of the UPS (E1 enzymes) as therapeutic targets in lymphoma. Moreover, the lab recently set out to advance understanding of the effect of targeted therapies on T-cell function, thus hoping to inform progress in immunooncology.

1. Novel targets within the ubiquitin-proteasome system:

  • Nedd8-activating enzyme as a tractable target in lymphoma and the role of neddylation in T-cell biology
  • Sumoylation in cancer: role in drug resistance and functional significance of pharmacologic inhibition of sumoylation in lymphoma
  • Ubiquitin-activating enzyme as a novel target in lymphoma. While proteasome inhibitors have shown efficacy in certain blood cancers, UAE inhibition may have several advantages and prove more efficacious

2. Cyclin-dependent kinases as targets in cancer, with particular focus on transcriptional CDKs (CDK9)

Deregulated expression of MYC is both sufficient for tumor initiation and indispensable for tumor maintenance, and thus inhibiting MYC function is an attractive therapeutic strategy. Importantly, Eμ-driven MYC induces lymphoid malignancies in transgenic mice, and second hits affecting regulators of apoptosis (BCL2, TP53) enhance MYC transformation. Use of bromodomain protein inhibitors determined feasibility of Myc suppression in pre-clinical models. In our laboratory, we study novel approaches to deregulate Myc in NHL, with particular focus on CDK9.