Publications

Human pluripotent stem cells (hPS cells) are rapidly emerging as a powerful tool for biomedical discovery. The advent of human induced pluripotent stem cells (hiPS cells) with human embryonic stem (hES)-cell-like properties has led to hPS cells with disease-specific genetic backgrounds for in vitro disease modeling and drug discovery as well as mechanistic and developmental studies. To fully realize this potential, it will be necessary to modify the genome of hPS cells with precision and flexibility. Pioneering experiments utilizing site-specific double-strand break (DSB)-mediated genome engineering tools, including zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), have paved the way to genome engineering in previously recalcitrant systems such as hPS cells. However, these methods are technically cumbersome and require significant expertise, which has limited adoption. A major recent advance involving the clustered regularly interspaced short palindromic repeats (CRISPR) endonuclease has dramatically simplified the effort required for genome engineering and will likely be adopted widely as the most rapid and flexible system for genome editing in hPS cells. In this unit, we describe commonly practiced methods for CRISPR endonuclease genomic editing of hPS cells into cell lines containing genomes altered by insertion/deletion (indel) mutagenesis or insertion of recombinant genomic DNA.

Despite improvements in overall health of the American population, disparities persist, particularly for minority women. The Affordable Care Act (ACA) offers the potential to reduce disparities through expanded insurance coverage, greater access to high-quality care, and bolstered prevention efforts in the context of new models of care such as the patient-centered medical home (PCMH). We use case studies representing three clinical conditions (breast cancer, HIV, and coronary heart disease) to present strategies for how a PCMH could reduce disparities for minority women. The case studies highlight the opportunity that further implementation of the ACA provides to improve screening, risk assessment, and prevention for a range of conditions that impact the health of minority women, as well as areas ripe for future investigation.