Systems Bioengineering: Modeling Angiogenesis and Mapping the Gene Therapy Industry

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In this dissertation, I recount my contributions to the emerging discipline of systems bioengineering in two contexts: expanding our ability to simulate the biomolecular circuitry underlying blood vessel growth; and developing a business to reduce the cost of life-saving gene therapies by filling gaps in the network of firms behind drug development and manufacturing. A rapidly advancing set of experimental and computational tools have enabled vascular biologists to build increasingly complex in silico recreations of angiogenesis – the process by which new blood vessels sprout from pre-existing vasculature – hinting at future where specialized biomedical software helps predict tissue vascularization in regenerative medicine and oncology. I combined rigorous mathematical analysis with a broad search for potentially interacting signaling processes within the vascular endothelial cells to show why the orthodox view of “tip cell selection” (a sub-process within angiogenesis) is unlikely to recapitulate the full range of observed angiogenic sprouting behaviors. I propose two qualitatively new hypotheses for the molecular underpinnings of tip cell selection which could predict angiogenic phenomena that previous simulations have failed to capture. Code samples for the mechanisms analyzed are included as supplements. Gene therapies using recombinant adeno-associated viruses (AAV) to deliver DNA into a patient's cells have reached market access in Europe, with the US expected to soon follow. AAV gene therapies might permanently cure hereditary diseases such as hemophilia and amyotrophic lateral sclerosis, but many emerging treatments are plagued by extraordinarily high manufacturing costs (some in excess of $1 million per patient). I pursued the goal of introducing a costing-saving technology – improved insect cell lines for use as a production substrate – into commercial use for AAV manufacturing. After performing in-depth industry analysis and business model design, I found that the raw price-performance was a minor component of the value that biotechnology firms placed on new manufacturing technologies. Rather, engineers attempting to solve real-world problems in biotechnology must account for a range of commercial, medical, legal, and social constraints to be successful – raising important implications for the future of systems bioengineering as it attempts to distinguish itself from its roots in basic research.

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Supplemental file(s) description: Code samples for simulating hypotheses for tip cell selection


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Chemical engineering


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Stroock, Abraham Duncan

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Varner, Jeffrey D.
Lucks, Julius

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Chemical Engineering

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Ph.D., Chemical Engineering

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Doctor of Philosophy

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Government Document




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Attribution-ShareAlike 2.0 Generic


dissertation or thesis

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