Global Translational Research

Aggressive Breast Cancer in Young Women in Ethiopia

Women in Ethiopia develop extremely aggressive breast cancer, and this can occur at very young ages such as their 20s or 30s. Our hypothesis is that tumors in Ethiopian women are more proteolytically active leading to aggressive growth and invasion. Proteolytic profiling would determine why some women present with more advanced tumors at earlier ages, but low cost methods are needed for practical translation to this beautiful country.

Low cost assays to monitor HIV disease progression and adherence to drug regimens

There is a need to develop affordable and reliable markers of adherence to antiretroviral therapy (ART), particularly for resource limited settings such as those in South Africa and Ethiopia, where we have established collaborations. We are currently applying our cathepsin zymography assay and applying it to studies of peripheral blood mononuclear cells, including monocytes and CD4+ T cells from HIV positive individuals. We investigated whether zymography could detect HIV disease progression or adherence to ARTs. Partnerships in Johannesburg, South Africa and Addis Ababa, Ethiopia

Vascular and orthopedic complications of sickle cell disease

Children with sickle cell disease have an 11% chance of suffering a major stroke by the age of 16, but 33% are at risk of having a silent stroke that impairs mental function and cognitive abilities. We are investigating the cellular and inflammatory mechanisms accelerating these destructive tissue remodeling.

Computational fluid dynamics of blood flow in the cerebrovasculature

Hemodynamic parameters of the blood in sickle cell disease change its properties and can influence cell and tissue mechanic properties in the vasculature. Computational fluid dynamics models of disturbed blood flow in these individuals are currently being developed using human data as well as transgenic mouse models in our research laboratory and with our collaborators in Beijing as part of BME PKU program.

Sickle Cell Large Artery Biomechanics and Imaging

Mechanical testing of carotid arteries and aortas from mice with sickle cell disease allows us to understand the changes to the elastin and collagen structures as they are remodeled due to upregulation of cathepsins in response to sickle cell disease. Cerebral arteries are more difficult to visualize so we use a label free method of magnetic resonance angiography.

Systems Biology and Personalized Medicine

Cathepsin Proteolytic Network Analyses

Personalized Proteolytic Potential to Predict Disease Progression and Response to Therapy

Emergent Behaviors of Integrated Cellular Systems

Fibrin(ogen)olytic Properties of Cysteine Cathepsins: Relevance for Biobots and in Sickle Cell Disease

Potential roles in destabilizing fibrin-based engineered living systems, and in abnormal blood clotting mechanisms in sickle cell disease.

Engineering Functional Time of Biological Machines

A combination of techniques from 3D printing, tissue engineering and biomaterials has yielded a new class of engineered biological robots that could be reliably controlled via applied signals. These machines are powered by a muscle strip composed of differentiated skeletal myofibers in a matrix of natural proteins, including fibrin, that provide physical support and cues to the cells as an engineered basement membrane. We examine the life expectancy, breakdown, and device failure of engineered skeletal muscle bio-bots as a result of degradation by proteases