Uncovering the Roles of Membraneless Organelles in Papillary Renal Cell Carcinoma
Abstract
Papillary renal-cell carcinoma (PRCC) is the second most common kidney cancer, with very little treatment options available. Service Members and Veterans are especially vulnerable to developing PRCC, since unsanitary water at deployment sites causes kidney diseases including kidney cancer. Additionally, a rare PRCC caused by the abnormal fusion of two segments of genomic DNA will disproportionally affect young Service Members, since these fusion kidney cancers mostly occur in children and young adults. Despite the risk and prevalence of PRCC in the American public, Service Members, and Veterans, its etiology remains unclear. In this proposal, we will tackle PRCC with a unique angle. We will focus on membraneless organelles (MLOs), tiny cellular bodies inside the PRCC cells that have long been used to diagnose PRCC, but with unknown functions. Our exciting preliminary data indicated that these membraneless organelles play important roles in PRCC progression. Building on these preliminary data, we aim to understand how MLOs form and function in PRCC, hoping to design novel PRCC therapies in the future targeting these MLOs. Our proposal aligns perfectly with the FY21 KCRP Focus Areas, by conducting basic biology research to better understand etiology and cancer progression, and by defining the biology of rare kidney cancers. Our research is highly innovative, since (1) we propose the paradigm-shifting idea that MLOs, the long-neglected cellular structures play essential roles in PRCC, and (2) we will design and utilize novel tools to characterize the MLOs in PRCC. The interim results from this research will first unveil all the molecular components of the MLOs in PRCC. This list of components will be essential for selecting the U.S. Food and Drug Administration-approved drugs that can target these components. From these drugs, we and the kidney cancer research community will identify the ones that can reliably modulate membraneless organelle formation in the cell model, mouse model, and in patients (3-5 years after project completion). Another interim result of this research is to determine the functions of the MLOs in PRCC, paramount for targeting these organelles for treatments. Consequently, the drugs that can modulate membraneless organelle formation, coupled with the knowledge of how MLOs regulate PRCC formation will be immensely useful for rationally selecting the drugs that can treat papillary renal cell carcinoma. The novel drug treatments that emerge from our study will greatly improve PRCC patient prognosis and prolong patient survival. This will in turn lead to enhanced PRCC patient outcome for Service Members, their families, Veterans, and the American public. In the kidney cancer research field, our research is impactful by bringing attention to the long-neglected MLOs in PRCC, promoting more research in understanding the roles of MLOs in PRCC and other kidney cancers. In the long term, research from our lab and from other labs on MLOs will lead to more rationally designed drug treatments targeting PRCC.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210900
Entities
People
- Danfeng Cai
Organizations
- Johns Hopkins University
- United States Army