Using experimental and theoretical approaches, we 1) develop acoustic technologies for cancer treatment and nerve regeneration and 2) study the interactions of blood cells (leukocytes, platelets, red blood cells), tissue resident cells (macrophages, mast cells), and circulating tumor cells with vascular and lymphatic endothelium under pathophysiological conditions such as inflammation, atherosclerosis, thrombosis, and cancer metastasis. We also develop novel methods for rheological 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.
|
Project 1: Quantitative Biomechanical Models of Circulating Cell Interactions
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 (dysfunctional) 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. Currently, it is not well understood how endothelial dysfunction and associated leukocyte adhesion develop in the body and how these pathophysiological
processes can be prevented or blocked without causing dangerous side effects. In our laboratory, we study the adhesion of leukocytes and other cirulating cells to
dysfunctional vascular or lymphatic endothelium 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 simulate both
passive and active deformation of adherent cells (Fig. 2) as well as cell adhesion to a compliant substrate.
Our computational algorithm can simulate the dynamics of multiple circulating cells with different deformability and size (Fig. 3). |
|
Project 2: Acoustic Technologies (HIFU, LIFU)
Focused ultrasound system. Our laboratory is equipped with a fully functional focused ultrasound system (Fig. 6). We built it in 2012, with funding received from
the Louisiana Board of Regents/National Science Foundation and Tulane University Senate Committee on Research. It operates at 1.1 MHz or 3.3 MHz frequency,
a continuous or pulsed mode, and a broad range of focal acoustic intensities (from 70 to 6000 W/cm2), i.e., it can be used for both low- and high-intensity
focused ultrasound (LIFU and HIFU) applications. Our focused ultrasound system is the only system available at Tulane University to conduct preclinical HIFU or
LIFU studies. Our current focus is to investigate the tumor destruction (ablation) by HIFU in tissue-mimicking phantoms, excised tissues, multicellular tumor
spheroids (Fig. 7), and in vivo (i.e., in mouse xenograft models) (Fig. 8). In this preclinical research, we test HIFU ablation of thyroid, liver, and prostate cancers
and collaborate with three clinicians from the Tulane University School of Medicine (Drs. Kandil, Buell, and Lee). We anticipate using this equipment for other
applications such as HIFU/LIFU-based adjuvant therapy for cardiovascular disorders and cancer or the LIFU stimulation of nerve regeneration after nerve injury. |
|
Project 3: Advanced Methods for Rheological Characterization of Biological Materials
|