Titles + affiliations
Assistant Adjunct Professor, Medicine
University of California, San Diego
The Role of Inflammation-Responsive R-Spondin Receptor Activation in Multiple Myeloma Stem Cell Generation
Multiple myeloma (MM) is the second most common blood cancer in the United States with over 32,000 new cases estimated in 2021. With a five-year survival rate of approximately 50%, more specific and effective prognostic tools and therapies for this disease are a vital unmet medical need for the >125,000 MM patients in the U.S. Myeloma remains incurable as a result of drug-resistant dormant cancer stem cells in the bone marrow that contribute to disease progression mediated by inflammatory cues. Currently, no clinical therapies target cancer stem cells in MM, in part because the identifying features of myeloma stem cells in the bone marrow remain elusive. The overall goal of this project is to explore a novel myeloma stem cell biomarker that may improve our ability to selectively identify and inhibit cancer stem cell generation in MM. The proposed biomarker, known as leucine-rich repeat-containing G protein-coupled receptor-4 (LGR4), is present on the surface of some myeloma cells but not normal B cell types. We predict that LGR4 could be exploited in the targeted detection and eradication of malignant myeloma stem cells. In this context, this New Investigator grant proposal aims to determine the extent to which inflammation-responsive activation or inhibition of LGR4 expression controls emergence of drug-resistant myeloma stem cells. The proposed research will set the stage for future clinical translation of more selective therapies for MM.
This grant had a significant, positive impact on our laboratory’s growth through career development as well as a scientific impact through its support of new discoveries in blood cancer research. First, this grant allowed us to generate a substantial amount of data that has formed the basis of new funding applications, one of which was recently funded with Dr. Crews receiving a prestigious Leukemia & Lymphoma Society Scholar Award. This new five-year award supports Dr. Crews’s myeloma research program as a whole, and thus the generous funding from the Leukemia Research Foundation enabled rapid growth of a young investigator’s lab. This grant also allowed two additional women scientists to participate and contribute to the research progress, and they were each recently accepted into PhD programs (The Rockefeller University and City of Hope) where they will continue their growth as biomedical researchers with an interest in blood cancer research. The results from this project will have a direct impact on future blood cancer research because we have identified new mechanisms through which myeloma cells may co-opt stem cell programs to regenerate disease, and these pathways can be targeted through genetic or cellular therapeutic strategies. Together, through this project we discovered that members of the Wnt/B-catenin signaling receptor family hold substantial promise for future anti-myeloma therapeutic development. New collaborations that were established during the course of this award period will also enable rapid translation of novel therapeutic strategies for the treatment of multiple myeloma and related plasma cell neoplasms.
Leukemia Research Foundation grant
$100K awarded in 2021
Cancer cell biology (cancer stem cells)