Research Sites and Projects

Bladder cancer is associated with risk factors that are common in Veteran and active-duty Service Member populations, including exposure to tobacco, Rainbow Herbicides (e.g., Agent Orange), industrial solvents, and radiation. Most patients suffering from metastatic bladder cancer do not survive despite surgery, radiation, chemo, targeted or immunotherapy. Our proposed research aims to use the principles of convergent science to identify and then target genes that are essential for the survival of cancer cells at metastatic site. In most cases, current treatment for metastatic bladder cancer is a “one size fits all” without consideration of molecular analysis of the tumor. Our approach will eventually lead to treatments specifically directed at the metastatic tumor, by targeting the “metastasis essentiality genes (MEGs)” that are uniquely present in each tumor. This approach may improve the survival of active military personnel, their family members and Veterans with metastatic bladder cancer. 

Sarcomas affect younger populations and account for >20% of pediatric solid malignancies and 8% of adolescent and young adult (AYA) cancers; this particularly affects military readiness as recruits and younger service members with children often belong to AYA groups. Our proposed research aims to improve diagnostics and prognostics that are predictive of resistance and metastasis in the current clinical framework with high-resolution personalized sarcoma molecular profiling, thus enabling the development and testing of novel therapeutic interventions. We will integrate molecular profiles from primary and metastatic tissues with comprehensive longitudinal liquid biopsy profiling of osteosarcoma and Ewing sarcoma patients. We hypothesize that there are analytes detectable in the tissue and liquid biopsies of sarcoma patients that can inform patient care and improve outcomes. Our approach will eventually lead to new tools to diagnose, monitor, and treat sarcoma by identifying molecular profiles, ultimately improving patient care and survival of active military personnel, their family members, and Veterans with sarcoma. 

Metastatic cancer treatments typically do not result in durable response and despite service members receiving high-quality cancer care, when the disease becomes metastatic, military health is severely impacted. Extrinsic determinants of cellular fitness that converge on a limited number of core pathways, suggesting that these processes are at least partially predictable and shared across cancers. We hypothesize that specific genomic drivers dictate metastatic proclivity and immune evasion, and thus will inform patient stratification for risk-assessment and therapy. Here we will evaluate these hypotheses by harnessing our custom database of uniformly analyzed genome/exome and transcriptome sequencing data from thousands of primary and metastatic cancers to define the molecular correlates of immune evasion, metastasis and treatment response. Our approach will distill the heterogeneity of metastatic disease to uncover shared molecular and microenvironmental features, thus nominating therapeutic vulnerabilities and approaches to patient stratification.