Morgan Lab Research
Multiple myeloma is a disease of malignant plasma cells that provides an excellent model system to understand the molecular basis of cancer progression. Our research team aims to understand the genetic and epigenetic basis for the transition of the premalignant to malignant phases myeloma and then to increasingly more aggressive leukemic states.
The process mediating these changes in behavior progressively deregulate a normal plasma cell conferring upon it inappropriate biological behavior for the bone marrow niche in which it is designed to live. We reason that if we can understand these abnormal biological programs, we will be able design novel therapeutic strategies that can effectively manipulate the behavior of the malignant plasma cells.
We think that a Darwinian model can explain the evolution of the disease through the recognized clinical phases of myeloma. This idea is based on the concept that a single germinal center B-cell is immortalized by either an immunoglobulin gene structural rearrangement or by the development of hyperdiploidy. This immortalized myeloma-propagating cell then randomly acquires genetic drivers that, when combined with selective pressures in the bone marrow, leads to the emergence of the best-adapted cells via an evolutionary process. Later in the evolutionary process, the clonal cells develop the ability to grow independent of the bone marrow microenvironment as plasma cell leukemia. This ongoing process creates a number of ecosystems, all of which have to be managed in the clinic. In this system, the rate of progression from pre-cancer to invasive-cancer reflects the balance of acquired genetic change in the tumor cells, which push the disease forward with the immune response to cancer cells acting to retard it.
Our aim is to understand how the genetic and epigenetic changes within clonal cells interact with the bone marrow and stromal microenvironment to mediate disease progression leading to invasive cancer. To this end, our laboratory has been set up for clinical translational research focused on collating and analyzing biological material from patients entered into structured clinical treatment protocols. This clinical material is processed into cellular subsets for downstream analysis often in the “core laboratories” of Perlmutter Cancer Center. We are focused on applying multiomic single cell analysis techniques to clinical material to discover cutting-edge insights into the interaction of clonal plasma cells with their supporting micro-environment.