Cell-based therapies are an exciting frontier in medicine. This field is built on a simple premise—cells can be engineered to recognize and treat various human diseases. The paradigm of cell-based therapy uses biosensors to interrogate a cell’s environment and distinguish disease from health, intracellular signaling pathways and genetic circuitry to...
Polycystic ovary syndrome (PCOS) is a complex genetic disorder characterized by hyperandrogenism, chronic anovulation, and polycystic ovarian morphology. PCOS affects up to 15% of premenopausal women worldwide, is the leading cause of anovulatory infertility, and is a major risk factor for type 2 diabetes. A number of susceptibility loci have...
The goal of the work reported here was to answer two important questions with regards to LTVV use for patients with ARDS: 1) How do we measure adoption? and 2) What are the drivers of provider adoption? To this end, I have demonstrated the influence of patient height, hypoxemia severity,...
Understanding the complex genome-phenome associations behind human complex traits will be a primary focus for the practice of precision medicine in the future. Identifying the genetic variants that contribute to the inter- and intra- phenotypic variations of individuals, elucidating pleiotropic architecture of common complex traits, and demonstrating how personal biomedical...
Periodic exposure to light and dark as a result of rotation of the Earth have served as a major evolutionary pressure to partition divergent biological processes to different phases of the day. Mammals display periods of activity/inactivity, wake/sleep, and feeding/fasting during distinct portions of the day. In mammals, these activities...
In the United States, allergic disease affects approximately 60 million people and impacts more people every year. While prevalence of allergic disease has steadily increased, there has concurrently been an increase in rates of metabolic syndrome—characterized by increased abdominal girth, decreased sensitivity to insulin, and higher levels of circulating blood...
Gastrointestinal (GI) colonization by Klebsiella pneumoniae is a risk factor for subsequent infection as well as transmission to other patients. Additionally, colonization is achieved by many strain types that exhibit high diversity in genetic content. However, how K. pneumoniae achieves colonization and whether the genetic factors it uses differ by...
The apolipoprotein E (APOE) E4 isoform is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). While APOE is predominantly expressed by astrocytes in the central nervous system, neuronal expression of APOE is of increasing interest in age-related cognitive impairment, neurological injury, and neurodegeneration. Here we show that endogenous...
Circulating tumor cell (CTC) clusters mediate metastasis at a higher efficiency compared to single cells and are associated with lower overall survival in breast cancer. However, the cellular heterogeneity and molecular mechanisms underlying CTC cluster formation and metastasis have yet to be fully elucidated. Combining single-cell RNA sequencing and flow...
Glioblastoma multiforme (GBM) is the most prevalent primary central nervous system tumor, characterized by resistance to therapeutic intervention, inevitable recurrence, and ultimately patient death. The dismal prognosis is due in part to underlying molecular factors that promote an intratumoral cellular state heterogeneity and protect tumor cells from cell death pathways....