Research in our laboratory focuses on understanding the mechanical and transport properties of biological systems at cellular and tissue levels. Using both computational and experimental approaches, we study the interactions of blood cells (leukocytes, platelets, red blood cells), tissue resident cells (macrophages, mast cells), and circulating tumor cells with vascular endothelium under pathophysiological conditions such as inflammation, atherosclerosis, thrombosis, sickle cell disease, and cancer metastasis. Another aspect of our research is tumor ablation where we study the mechanical destruction of tumor tissue by cavitation bubbles generated by high-intensity focused ultrasound. We also develop novel rheological methods for characterization of living cells and tissues and use our state-of-the-art computational fluid dynamics models to predict blood flow in vessels with complex geometry. Below you will find a short description of our current research projects.
Inflammation. Blood-borne leukocytes (white blood cells) are the first
line of defense against invading pathogens. They are recruited from peripheral
blood into infected tissues during inflammation through a complex series of
events involving leukocyte capture by activated endothelial cells, leukocyte
rolling on and firm adhesion to endothelium, and leukocyte transendothelial
migration (diapedesis). These events, collectively known as leukocyte extravasation or leukocyte adhesion
cascade, are mediated by the interplay of inflammatory mediators and cell
adhesion molecules of the selectin and integrin families. In our laboratory,
we study the leukocyte adhesion cascade by using in vitro systems
(a parallel-plate flow chamber and
Bioflux 200 microfluidic shear flow system that permits up to 24 cell
adhesion assays in parallel, Fig. 1) and our custom three-dimensional computational
algoritm of deformable cell adhesion, known as VECAM (ViscoElastic Cell Adhesion Model). VECAM can predict both
passive and active deformation of adherent cells (Fig. 2) as well as cell adhesion to a compliant substrate.
Understanding the leukocyte adhesion cascade is critical to the development of therapies
for inflammatory disorders.
Motivation. Image-guided tumor ablation is a non-surgical treatment option for cancer.
In this approach, the destruction of cancerous masses is achieved through direct, local application of
a chemical agent or through localized heating of tumor tissue via the absorption of the electromagnetic
or acoustic wave energy. Although the existing tumor ablation modalities treat well small tumors, they are largely ineffective
for metastases and single tumor lesions greater than 5 cm in size. The overall goal of this project is to develop a novel method for
controlled ablation of large and metastatic tumor masses in which high intensity focused ultrasound (HIFU) will be complemented with
the techniques that reduce the cavitation threshold locally in the tumor. Our current focus is on the combination of HIFU and
percutaneous ethanol injection (PEI). The proposed activities may ultimately provide a non-surgical treatment option for patients
with late-stage cancer.
In this project, we use computational fluid dynamics to study blood flow
in the human vertebrobasilar system (ones of the major arteries in the brain) under normal conditions
and in the presence of one or several aneurysms (including the case of a giant aneurysm that forms
as a result of coalescense of two aneurysms, Fig. 9). The geometry of our computational models is reconstructed
from the images of the vessels extracted from deceased patients in the laboratory of our collaborator (Dr. Arthur Ulm) in the
Department of Neurosurgery at the LSU Health Sciences Center. Using our model, we determine "weak spots" in the vessel walls
at which new aneurysms
can develop. We also study through numerical simulations whether surgical treatment of intracranial
aneurysms (e.g., filling an aneurysm with wires or Onyx solution) may lead to further complications.
Project 4. Development of Novel Methods for Rheological Characterization of Biological