Cell-autonomous and non-autonomous mechanisms of minimal residual disease persistence in multiple myeloma: mechanistic and translational implications.
Our laboratory is focused on elucidating tumor cell-autonomous and non- autonomous mechanisms of minimal residual disease persistence in multiple myeloma, as a step towards devising curative therapeutic approaches. Minimal residual disease following treatment with traditional and novel agents and/or autologous transplantation is reliably predictive of relapse and adverse clinical outcomes. To study tumor cell-autonomous mechanisms, we are pursuing the powerful approach of avian leukosis virus-mediated gene transfer using an in vivo model the PI developed as a postdoctoral fellow in the Varmus lab (Prdm-1:TVB). This model has been crossed to the preclinically-validated Vk*MYC myeloma model in order to permit the flexible genetic manipulation of Vk*MYC in a controlled and tissue-specific fashion. Our lab possesses special expertise in transduction of lymphoid cells using avian-pseudotyped oncoretroviral and lentiviral vectors. On the non-cell autonomous level, we have focused on the mechanisms underlying polarization and activation of macrophages in the myeloma niche and their therapeutic exploitation. Lastly, we have embarked on an exciting collaboration with Professor David C. Schwartz to characterize the genomic determinants of drug resistance in myeloma through optical mapping, an innovative structural genome analysis platform and pipeline developed by Professor Schwartz at UW-Madison.