Global Translational Research

HIV and Cardiovascular Disease in the US and Abroad


The success of highly active antiretroviral therapy (HAART) has transformed HIV-infection from a terminal diagnosis to a manageable chronic disease. HIV-infected children and adults, however, have shown elevated incidence of atherosclerosis, pulmonary arterial hypertension, and cerebrovascular complications. Our work seeks to develop novel tissue engineered experimental platform to study human cardiovascular events due to HIV infection, and to use animal native artery studies to guide tissue engineered strategies and parse mechanisms that are viral protein mediated from those due to active virus.

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

Strokes in children with sickle cell disease


Children with sickle cell disease have an 11% chance of suffering a major stroke by the age of 16, and there is a 221-fold increase in their risk of stroke. Silent strokes lead to impaired mental function and cognitive abilities during development, and massive strokes can be fatal. Cell-cell interactions and the inflammatory conditions characteristic of sickle cell disease lead to accelerated arterial remodeling in pediatric patients causing strokes.

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. CFD models of disturbed blood flow in these individuals are currently being developed and then actuated in bioreactors in our research laboratory.

Tissue Engineered Models of Human Disease

Tissue Engineered Human Artery


By creating tissue engineered models, we are able to study human mechanisms with human cells in engineered environments that recapitulate the in vivo situation but provides a level of manipulation to ask meaning scientific questions about the disease pathology. We are currently using tissue engineered arteries comprised of human cells for testing physiological blood flows and effects on human cells capable of being infected by HIV. We are also using these tissue engineered arteries for studies of altered hemodynamics with plasma and red blood cells from people with sickle cell disease to understand mechanisms of sickle-induced damage to the arterial wall.

Tissue Engineered Bone Marrow Microenvironment

Another example of this work is that we have been collaborating with Dr. Shelly Peyton at University of Massachusetts-Amherst to develop tissue engineered models of metastatic cancer into the bone marrow with fluorescent reporter signatures

Systems Biology and Personalized Medicine

Cathepsins Cannibalism in Cardiovascular Disease

Personalized Proteolytic Potential to Predict Disease Progression

Emergent Behaviors of Integrated Cellular Systems

EBICS


By creating tissue engineered models, we are able to study human mechanisms with human cells in engineered environments that recapitulate the in vivo situation but provides a level of manipulation to ask meaning scientific questions about the disease pathology. We are currently using tissue engineered arteries comprised of human cells for testing physiological blood flows and effects on human cells capable of being infected by HIV. We are also using these tissue engineered arteries for studies of altered hemodynamics with plasma and red blood cells from people with sickle cell disease to understand mechanisms of sickle-induced damage to the arterial wall.