Srividya Swaminathan, Ph.D.

Project: Targeting the Long Isoform of the Prolactin Receptor to Prevent B-Lymphomas
Named Award: Congressional Families Program: Tribute to The Honorable Vic Fazio
Position Assistant Professor, Systems Biology
Institution: Beckman Research Institute of the City of Hope, Duarte, Calif.

Research Overview

Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of blood cancer of a type of immune cell known as the B cell. Unfortunately, around 40% of people with DLBCL do not survive five years and beyond after their initial diagnosis. Safe preventative interventions for DLBCL remain an urgent clinical need. Development of such interventions requires an understanding of how DLBCLs are initiated and established at a molecular level.

During the initiation phase of DLBCL, normal B cells become pre-malignant B cells. These pre-malignant B cells then establish full-blown DLBCL. At this stage, the clinical symptoms of DLBCL become apparent. Our recent studies find that the sex hormone prolactin (PRL), which is elevated during acute and chronic stress in both males and females, initiates and establishes DLBCL. We find that PRL increases the risk of B cells transforming into deadly DLBCL in vulnerable people with autoimmune diseases and in those with milder forms of lymphoma. PRL achieves this by binding to a specific form of its receptor on B cells called the ‘long form prolactin receptor (LFPRLR)’.

Our proposed study will solidify the mechanisms by which PRL, through the LFPRLR, turns B cells malignant and ultimately establishes full-blown DLBCL.

Our findings will inform:

Development of strategies to measure the elevation in the lymphoma-promoting LFPRLR in people at increased risk of DLBCL.
Clinical application of safe agents that block the production of the LFPRLR, such as those used in this project, to prevent DLBCL in vulnerable populations with B cell-mediated autoimmune diseases and slow-growing B-cell lymphomas.

My “Why”

Each year, many children and adults are diagnosed with deadly forms of blood cancer of a type of immune cell known as the B cell. These cancers are particularly difficult and expensive to treat. There is an unmet clinical need in prevention and early diagnosis of B-cell malignancies, especially in people vulnerable to developing these dreadful cancers.

Why Funding Matters

Because most resources are currently concentrated in treating blood cancers rather than preventing them, funds from the Prevent Cancer Foundation will allow us to advance research in blood cancer prevention. Specifically, this support will enable us to conduct essential preclinical studies that strengthen the safety and effectiveness of our proposed approach in preventing diffuse large B-cell lymphomas.