Richard and Loan Hill Professor
A new approach for replacement trachea
Eben Alsberg and his colleagues are pioneering a new method for growing human windpipes to help people who have suffered trachea damage or loss, borrowing conceptually from a toy that many people are familiar with: Lego. In the team’s unique approach, modules of tissue are formed using a patient’s cells, and these modules can then be assembled into more complex tissue. If Dr. Alsberg and colleagues are successful, trials and further research and development could someday give surgeons the option of replacing damaged or ill-functioning trachea with fully functional natural-tissue replacement trachea. The goal is for the replacement windpipes to fulfill three criteria that are essential to success: to stay rigid, preventing airway collapse when the patient breathes; to contain immunoprotective respiratory epithelium, the tissue lining the respiratory tract, which moistens and protects the airway and functions as a barrier to potential pathogens and foreign particles; and to integrate with the host vasculature, or system of blood vessels, to support epithelium viability. Initial tests show promise that Dr. Alsberg and colleagues’ approach has the potential to meet all three of these standards, and if the technique can be used successfully for human trachea, the research team hopes that it may provide insight into a new way to engineer other complex tissues and organs as well.
Richard and Loan Hill Professor
Automated classification of eye disease
Xincheng Yao’s research seeks to develop a comprehensive computer aided diagnosis (CAD) system that can be extensively used by clinicians for regular screening of patients with retinal diseases. The automated algorithms and software packages developed by Dr. Yao and his research team utilize image processing and machine learning to quantify morphological distortions in human retina and identify different stages of common eye diseases such as diabetic retinopathy. The team primarily works with an imaging modality called optical coherence tomography angiography (OCTA), which can capture capillary-level blood vessel structures in different retinal layers with high resolution. Using quantitative OCTA biomarkers, the algorithm has proven able to identify the onset of diabetic retinopathy and predict the progression of the disease. These algorithms have wider potential, too: they can be adapted for automated classification of age-related macular degeneration, glaucoma, and other eye diseases that are known to cause distortions of retinal blood vasculatures.
Dr. Yao’s team recently published a new paper on OCTA quantitative analysis and automated classification. Links to that and all of Dr. Yao’s relevant research can be found on this page.
Many organisms produce minerals during various biological processes through biomineralization. These natural processes include bone formation, enamel deposition, iron storage in proteins, and kidney stone formation. In situ electron microscopy is one technique that is being used to visualize these processes at nanoscale. Tolou Shokuhfar and her research team are conducting related investigations, studying the regulation of iron ions in the human body. They were able to investigate the biomineralization process inside iron-storage ferritin proteins at an atomic scale—a first for the field. The findings from this work may be useful in determining methods of reducing the incidence of Parkinson’s and Alzheimer’s diseases, which are linked to iron storage. In other projects, Dr. Shokuhfar and her team are studying the formation mechanisms of calcium oxalate (CaOx) biominerals, which are responsible for kidney stone disease, and the formation of magnetic nanoparticles by magnetotactic bacteria—all drawing on the power of in situ electron microscopy.
Liver Platforms for Drug Toxicity Testing
The liver, the largest internal organ, carries out more than 500 functions that are important for life, including breaking down most of the therapeutic drugs that human beings take. Because of this critical role, the liver is also a target for many drugs’ toxicity, a property that causes some pharmaceuticals to be withdrawn from the market by the U.S. Food and Drug Administration. Testing drugs for toxicity before they enter the market is crucial, but testing drugs on animals is not an ideal solution due to significant differences between how the livers of animals and humans metabolize drugs. Salman Khetani’s Microfabricated Tissue Models (MTM) laboratory addresses this problem by using bioengineering technologies to create miniaturized human liver tissues using cells from livers donated to science. These “mini” human livers can survive on a “chip” (akin to a microchip inside a computer) outside the body for many weeks, and they have been used successfully by many pharmaceutical companies to test the toxic effects of drugs before the drugs are put into live patients, safeguarding patient safety and health. These mini livers also are being used to discover new therapies for diseases such as hepatitis B virus infection, which afflicts more than 300 million people globally.