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.
- A Phase Ib/II study of Syk inhibitor entospletinib (GS-9973) in combination with obinutuzumab in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and B-cell malignancies
- A Phase I Study of pevonedistat (MLN4924) in combination with ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and non-Hodgkin lymphoma
- A Phase I Study of PI3Kα,δ Inhibitor Copanlisib in Combination with PD-1 Antagonist Nivolumab in Patients with Transformed Chronic Lymphocytic Leukemia (Richter's Transformation) or Non-Hodgkin Lymphoma
- Effect of comorbidities on treatment outcomes in chronic lymphocytic leukemia
Alexey Danilov, M.D., Ph.D.
Yaroslavl Medical Academy, Russia
Residency, Internal Medicine, Brown University, Providence, RI
Fellowship, Hematology-Oncology, Tufts University, Boston, MA
B.S., Portland State University
Senior Research Assistant
B.S., Portland State University
Tingting Liu, Ph.D.
Adam Kittai, M.D.
- Claire Godbersen, Senior Research Assistant
- Cody Paiva, Research Alumni
Max Gordon wins Abstract Achievement Award at the 60th ASH Annual Meeting in Atlanta for his presentation "Impact of individual comorbidities on treatment outcomes in chronic lymphocytic leukemia"
Scott Best wins Best Abstract Award for his oral presentation "TAK-243, a small molecule inhibitor of ubiquitin-activating enzyme (UAE), induces ER stress and apoptosis in CLL cells" at the Young Investigator Meeting at the International Workshop on CLL in Cologne, Germany
Alexey Danilov becomes a Leukemia and Lymphoma Society Scholar in Clinical Research
Max Gordon wins Abstract Achievement Award at the 59th ASH Annual Meeting in Atlanta for his oral presentation "Medical comorbidities assessed by CIRS negatively impact survival in the era of targeted therapies in CLL: a multicenter retrospective analysis"
Scott Best wins Abstract Achievement Award at the 59th ASH Annual Meeting in Atlanta for his presentation "TAK-243, a small molecule inhibitor of ubiquitin-activating enzyme, induces ER stress and apoptosis in diffuse large B-cell lymphoma cells"
Danilov lab awarded a Leukemia and Lymphoma Society Translational Research Program award
Taylor Hashiguchi gives an oral presentation at the 58th ASH Annual Meeting in San Diego "Selective targeting cyclin-dependent kinase-9 (CDK9) downmodulates c-MYC and induces apoptosis in diffuse large B-cell lymphoma (DLBCL) cells"
Cody Paiva wins Abstract Achievement Award at the 58th ASH Annual Meeting in San Diego for his oral presentation "SYK inhibition disrupts the cross-talk between B-cell activation factor (BAFF) and B-cell receptor (BCR) and thereby antagonizes Mcl-1 in CLL B-cells"
Alexey Danilov becomes a Lymphoma Research Foundation Clinical Investigator