Sickle Cell Disease
Sickle cell disease is a devastating genetic disorder affecting more than 70,000 people in the United States and more than 13 million worldwide. The disease is hereditary and is best known for the abnormal crescent shape of patients’ red blood cells. Individuals living with this disease suffer from chronic pain and fatigue, among other symptoms, which result in frequent hospitalization, and the average lifespan of a person living with this disorder is less than 49 in the U.S. In some parts of Africa, where the disease is endemic, almost half the children born with this disease will die before age 5. In addition to the human cost, the financial burden of this disease is enormous with medical costs exceeding $1.1 billion annually in the U.S.
Our group has a major effort to build tools that allow us to better study but also diagnose and develop treatments for sickle cell disease. At its core, sickle cell disease is a blood flow disorder, caused when diseased red blood cells stiffen upon deoxygenation in the capillary beds. That stiffening can lead to jamming and blockage of blood flow, precipitating a “vaso-occlusive crisis” or “VOC”. Our goal is to build tools that allow us to study this VOC process in vitro. This requires us to build devices that mimic the size scale of blood vessels as well as the oxygen transport between the blood and surrounding tissue. Additionally, we want to capture other important biological components such as interactions with the vascular endothelium and immune cells. In addition to studying the disease from a scientific perspective, we also want to build devices that help us better diagnose disease severity and evaluate treatment regimens, and we want to build platforms that can be used to develop new treatments, which are so desparately needed.
A tumor is an extremely complex tissue, incorporating a variety of matrix, stroma, soluble factors, and other cues. Moreover, tumors incorporate unique characteristics, such as a disorganized vasculature and hypoxic regions, that are not seen in other tissue types. Unfortunately, we can only study this complexity in vivo, where the number of tools and probes available is limited as is the throughput of experiments. One of the thrusts of our lab is to develop in vitro tumor models that incorporate many of the key microenvironmental cues that affect tumor development as well as the unique vascular architecture. One of the major challenges in tissue engineering is to create vasculature in artificial tissues that resembles vasculature in vitro. We’re trying to use fluid mechanical principles to automatically self-assemble micro-scale tissue building blocks into macro-scale vascularized tissues. Using this in vitro tumor model, we are trying to better understand the process of metastasis – how cancer cells spread through the vasculature from one site to another – as well as how novel therapeutics – nanoparticles carrying chemotherapeutics or gene silencing siRNA – are most efficiently delivered to a tumor. This work combines tissue engineering, biomaterials, fluid mechanics, and microfluidics to solve critical challenges in tissue engineering, cancer biology, and tumor therapy.
Low Cost Diagnostics
While we are very privileged to live in the United States, where we have access to excellent health care, not everyone in the world is so lucky. Some years back I traveled to Nicaragua with some colleagues, and I had my eyes opened to a new reality of health care. As engineers, we have have a great opportunity to impact global health through innovative technologies that provide low cost, robust solutions for diagnosis and treatment of disease. Our team is working on a number of new tools that we hope will make a difference.