My ultimate goal is to become an independent cancer researcher with a program that bridges genetic discovery and implementation science for common and complex cancers. My predoctoral training in genomic discovery and my postdoctoral direction in implementation science will build solid ‘research pillars’ to support my independent research program bridging translational genomic science. My F99 training will provide expertise in genomic discovery by tackling critical barriers that exist for common and complex cancers, including: germline genetic and tumor heterogeneity, and mapping functional variants for genomewide association studies (GWAS) loci. Cancers are phenotypically complex, with multiple germline risk variants and tumors that exhibit different molecular profiles. These heterogeneities complicate studies attempting to identify factors influencing risk, prognosis, and response to therapies or other clinical outcomes. GWASs have identified many significant, common, low-risk loci, but the functional variants driving GWAS signals are largely unmapped. Further, the vast majority of heritability is unexplained, and rare variants are largely undiscovered. In my recent first-author publication, I propose a novel method to address germline genetic heterogeneity in high-risk pedigree studies. I applied this method to myeloma to discover the first, segregating risk variants for the disease (Waller et al, PLoS Genetics, 2018). I have subsequently expanded the approach to identify overlapping evidence from multiple pedigrees, uncovering additional regions likely to harbor rare-risk variants (Waller et al, in preparation). I have also investigated strategies to utilize family-based data to map functional variants at GWAS loci (Waller et al, in preparation). During the F99 phase, I will complete my graduate work in discovery with novel methods to improve molecular characterization of myeloma tumors, another strategy to combat heterogeneity. My F99 training will also prepare me for my postdoctoral direction in implementation science by tackling barriers to the use of family- health history (FHx) in primary care. Genetic discoveries are rapidly advancing, but personalizing clinical screenings and implementing complex, patient-specific risk assessments is challenging in today’s overwhelmed primary care settings. FHx is still the most valuable piece of information a clinician and patient have to identify potential health risks and personalize care. However, FHx remains largely underutilized in routine cancer prevention due to low collection and low adoption of evidence-based guidelines. In my F99, I will investigate the impact of FHx documentation workflows on compliance with cancer screening guidelines. For my postdoctoral work (K00 phase), I will identify research and training experiences to build expertise in implementation science for genomic medicine. Specifically, one research project I could pursue is a feasibility study of implementing proven risk com...