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...
Over the past fifty years, techniques for synthesizing and manipulating matter on the 1-100 nanometer scale have led to the development of nanoparticle-based approaches to both disease diagnosis and treatment. The modification of nanoparticles with biological macromolecules such as proteins and nucleic acids has led to the development of highly...
This dissertation focuses on the development of quantitative approaches for characterizing endogenous signaling pathways and designing new pathways in mammalian cells. I demonstrate how mathematical descriptions that are formulated to explain gene expression patterns can also serve as a powerful springboard for deeper analyses into the properties and functions of...
The engineering of human reproduction is one of the defining scientific advances of the past century. Methods to specifically engineer the testis have an equally long and rich history, and have experienced significant progress over the past two decades, leading to current-day breakthroughs which are shifting the paradigms by which...
Proteins represent a critical class of biomolecules, universally employed by all living organisms to fulfill essential structural, functional, and enzymatic roles necessary to support life. In nature, these polymers are composed generally of twenty natural amino acid (AA) building blocks, which can be modified with covalent adducts known as post-translational...
Platelets are circulating anucleate discs derived from megakaryocytes, and play major roles in hemostasis, inflammation, thrombosis, and vascular biology. Multi-phase culture systems for inducing in vitro platelet production from mature megakaryocytes have been explored to allow progenitor expansion, megakaryocyte maturation, and promotion of platelet formation and shedding. In this thesis,...
End-stage renal disease, or kidney failure, can result from acute kidney injury or sustained kidney damage in the form of chronic kidney disease. As the prevalence of end-stage renal disease continues to rise, the gold-standard treatment—kidney transplantation—is increasingly restricted by the shortage of transplantable donor kidneys. Bioengineered kidney tissues may...
The work in this thesis focuses on computational methods for the identification of novel enzymatic pathways. In particular this work focuses on the utilization of the Biological Network Integrated Computational Explorer (BNICE) software suite to predict de novo enzymatic pathways for the production of commercially relevant compounds and on improvements...
Currently, platelet transfusions, possessing profound clinical importance in the clotting of blood and healing of wounds, are entirely derived from human volunteer donors. This approach is limited by a 5-day shelf life, the potential risk of contamination, and differences in donor/recipient immunology. In vivo, platelets are formed when bone marrow...
More than half of proteins in humans are modified with carbohydrates in a process called glycosylation, yet this process remains poorly understood even though approximately 1% of the expressed human genome encodes biosynthetic machinery for glycosylation. Unlike genomics and proteomics where high throughput tools are now routinely used to generate...