Leslie Crews, PhD

University of California, San Diego

Titles + affiliations

Assistant Adjunct Professor, Medicine
University of California, San Diego

Research

The Role of Inflammation-Responsive R-Spondin Receptor Activation in Multiple Myeloma Stem Cell Generation

Summary

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.

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Leukemia Research Foundation grant
$100K awarded in 2021

Disease focus
Multiple myeloma

Research focus
Cancer cell biology (cancer stem cells)