Immunoengineering, cancer, metastasis, immunotherapy, drug delivery
Dr. Thomas’s research focuses on the role of biological transport phenomena in physiological and pathophysiological processes. Her laboratory specializes in incorporating mechanics with cell engineering, biochemistry, biomaterials, and immunology in order to 1) elucidate the role mechanical forces play in regulating seemingly unrelated aspects of tumor progression such as metastasis and immune suppression as well as 2) develop novel immunotherapeutics to treat cancer.
Cancer progression is tightly linked to the ability of malignant cells to exploit the immune system to promote survival. Insight into immune function can therefore be gained from understanding how tumors exploit immunity. Conversely, this interplay makes the concept of harnessing the immune system to combat cancer an intriguing approach. Using an interdisciplinary approach, we aim to develop a novel systems-oriented framework to quantitatively analyze immune function in cancer. This multifaceted methodology to study tumor immunity will not only contribute to fundamental questions regarding how to harness immune response, but will also pave the way for novel engineering approaches to treat cancer such as with vaccines and cell- or molecular-based therapies.
Dr. Sulchek's research focuses primarily on the measurement and prediction of how multiple individual biological bonds produce a coordinated function within molecular and cellular systems. There are two complementary goals. The first is to understand the kinetics of multivalent pharmaceuticals during their targeting of disease markers; the second is to quantify the host cell signal transduction resulting from pathogen invasion. Several tools are developed and employed to accomplish these goals. The primary platform for study is the atomic force microscope (AFM), which controls the 3-D positioning of biologically functionalized micro- and nanoscale mechanical probes. Interactions between biological molecules are quantified in a technique called force spectroscopy. Membrane protein solubilized nanolipoprotein particles (NLPs) are also used to functionalize micro/nano-scale probes with relevant biological mediators. This scientific program requires the development of enabling instrumentation and techniques, which include the following:
Advanced microscopy and MEMs;
Nanomechanical linkers, which provide a convenient platform to control biomolecular interactions and study multivalent molecular kinetics;
Biological mimetics, which provide a simple system to study cell membranes and pathogens.
Ultimately, this work is used to optimize molecular drug targeting, improve chem/bio sensors, and develop more efficient pathogen countermeasures.
Dr. García's research centers on cellular and tissue engineering, areas which integrate engineering and biological principles to control cell function in order to restore and/or enhance function in injured or diseased organs. Specifically, his research focuses on fundamental structure-function relationships governing cell-biomaterials interactions for bone and muscle applications. Current projects involve the analysis and manipulation of cell adhesion receptors and their extracellular matrix ligands. For example, a mechanochemical system has been developed to analyze the contributions of receptor binding, clustering, and interactions with other cellular structural proteins to cell adhesion strength.
In another research thrust, bio-inspired surfaces, including micropatterned substrates, are engineered to control cell adhesion in order to direct signaling and cell function. For instance, biomolecular surfaces have been engineered to target specific adhesion receptors to modulate cell signaling and differentiation. These biomolecular strategies are applicable to the development of 3D hybrid scaffolds for enhanced tissue reconstruction,"smart" biomaterials, and cell growth supports. Finally, genetic engineering approaches have been applied to engineer cells that form bone tissue for use in the development of mineralized templates for enhanced bone repair.
Dr. Vito's research interest is in the mechanical determinants of rupture of atherosclerotic plaque. Plaque rupture is important in stroke and heart attack because it precipitates the formation of a thrombus (blood clot) which then breaks away and causes an obstruction of flow. Experiments and modeling are used to determine what compositional factors predispose a plaque to rupture. Dr. Vito collaborates with people interested in detecting vulnerable plaque using magnetic resonance imaging and with others who want to intervene with drugs or genetic manipulation to reduce the likelihood of plaque rupture. His current research is sponsored by the National Science Foundation.
Microdevices for Drug & Gene Delivery, MEMS Ion Sources for Bioanalytical Mass Spectrometry, Scanning Probes for BioElectroChemical Imaging on Nanoscale, Thermomechanical Aspects of Tissue Repair & Regeneration, Lab-on-a-Chip Instrumentation
Dr. Fedorov’s research is at the interface of basic sciences and engineering. His research portfolio is diverse, covering the areas of portable/ distributed power generation with synergetic carbon dioxide management, including hydrogen/CO2 separation/capture and energy storage, novel approaches to nanomanufacturing (see Figure), microdevices (MEMS) and instrumentation for biomedical research, and thermal management of high performance electronics. Dr. Fedorov's research includes experimental and theoretical components, as he seeks to develop innovative design solutions for the engineering systems whose optimal operation and enhanced functionality require fundamental understanding of thermal/fluid sciences.
Applications of Dr. Fedorov’s research range from fuel reformation and hydrogen generation for fuel cells to cooling of computer chips, from lab-on-a-chip microarrays for high throughput biomedical analysis to mechanosensing and biochemical imaging of biological membranes on nanoscale.
The graduate and undergraduate students working with Dr. Fedorov's lab have a unique opportunity to develop skills in a number of disciplines in addition to traditional thermal/fluid sciences because of the highly interdisciplinary nature of their thesis research. Most students take courses and perform experimental and theoretical research in chemical engineering and applied physics. Acquired knowledge and skills are essential to starting and developing a successful career in academia as well as in many industries ranging from automotive, petrochemical and manufacturing to electronics to bioanalytical instrumentation and MEMS.
Dr. Kim’s research focuses on developing biomimetic microsystems that reconstitute organ-level functions on chip and integrative control systems that allow large-scale production of therapeutic and diagnostic bio/nanomaterials. His lab develops experimental control systems and micro/millifluidic platforms, and employs computer-aided engineering to understand: (1) how cells coordinate responses to signaling cues in multicellular environments; (2) how bio/nanomaterials assemble and break in dynamically controlled fluid flows; and (3) how biological systems interact with nanomaterials with varied physicochemical properties.
Organs-on-chips that mimic the characteristics of human organs are enabling scientists to predict more accurately how effective therapeutic drug candidates would be in clinical studies without serious adverse effects and to address how multiple cells coordinate organizational decisions in response to complicated signaling cascades. Dr. Kim’s lab builds valid artificial organ-on-a-chip systems by manipulating 3D extracellular environments in time and space, utilizing the expertise in microfabrication, miniaturization, robotics, and control systems engineering, and understanding the human body’s fundamental physiological responses to mechanochemical cues. This research will help examine the behavior and interaction of multifunctional nanomaterials with biologically relevant microenvironments for rapid clinical translation of nanomedicine, thereby bringing drugs to market more quickly and perhaps even eliminate the need for animal testing.
Advanced treatment of diseases such as cancer and atherosclerosis needs controlled delivery of multifunctional nanocarriers that contain multiple drugs that can target tumors with anti-angiogenic and cytostatic agents and a diversity of imaging agents that monitor the transport in the body. Optimized integration of manufacturing nanomaterials will contribute to advanced health technology not only because of rapid clinical translation of drugs but also due to reduction of any release of harmful byproducts. Dr. Kim’s lab designs and fabricates diverse microfluidic modules for diverse syntheses of multifunctional nanomaterials and integrates the modules to establish large-scale implementation of manufacturing processes scaled to economically and industrially relevant production level. The integrative system will facilitate good manufacturing practice (GMP) production and clinical translation in pharmaceutical and biomedical industry and enable reproducible and controlled synthesis of nanoparticles at scales suitable for rapid clinical development and commercialization.
Dr. Gleason's current research interest is in soft tissue biomechanics and growth and remodeling, with particular emphasis on native vascular tissues and tissue engineered constructs. Two key aims of his research are to develop mathematical theories for soft tissue growth and remodeling that allow for the incorporation of observations made at multiple length scales, and to develop novel experimental models to test the underlying assumptions of theoretical simulations that allow for parallel observations at different length scales.
It is unquestioned that cells can sense and respond to changes in loading. Increased load on focal adhesion sites in vascular smooth muscle, for example, can alter cell-signaling pathways, ultimately leading to altered gene expression. Altered gene expression can manifest itself in many different ways, including an altered production of vasoactive molecules, extracellular matrix and matrix-degrading proteins, cell cycle regulating signals, and cytoskeletal proteins, among many others. The net effect of these, and other, mechanotransduction pathways include increases in cell and matrix turnover, local growth (or atrophy), structural and functional remodeling of existing cells, and remodeling of matrix, cell-matrix and matrix-matrix interactions, all aimed, presumably, toward evolving the local mechanical environment from an undesirable' condition to a desirable' condition. Despite the explosion of information on tissue growth and remodeling, from molecular, intracellular, cellular, cell-matrix, organ, and whole organism levels, attempts at integrating these data into a predictive model is still in its infancy; there is a pressing need for such an integrative, multiscale model. Such predictive models will be essential to further our understanding of many physiological and pathophysiological processes and critical to aid in the development and optimization of clinical interventions and tissue engineering strategies.
Dr. Ku has an active interest in peripheral vascular pathology and unsteady, threedimensional fluid dynamics. One project investigates the relative role of hemodynamics and thrombosis in vascular graft occlusion. Additional studies involve the development of a tissue-engineered vascular graft. Noninvasive magnetic resonance imaging is used to determine the hemodynamics and detect pathology in vivo. Computational solutions explore fluid mechanic variations from geometry. Another project studies the collapsible tube behavior of highly stenotic arteries.
Dr. Ku has an active interest in cardiovascular pathophysiology, unsteady threedimensional fluid mechanics, medical implants, and commercialization of university research. Basic research focuses on sudden cardiac death from platelets subjected to high shear and plaque rupture due to arterial stenosis collapse. His research extends to Translational Technology using applied biomedical engineering to impact patient care and therapy. Projects span from device design to development of bench tests to predict clinical performance. Dr. Ku teaches entrepreneurship and product development to bring technological solutions to the bedside.
Dr. Hesketh's research interests are in Sensors and Micro/Nano-electro-mechanical Systems (MEMS/NEMS). Many sensors are built by micro/nanofabrication techniques and this provides a host of advantages including lower power consumption, small size and light weight. The issue of manipulation of the sample in addition to introduce it to the chemical sensor array is often achieved with microfluidics technology. Combining photolithographic processes to define three-dimensional structures can accomplish the necessary fluid handling, mixing, and separation through chromatography. For example, demonstration of miniature gas chromatography and liquid chromatography with micromachined separation columns demonstrates how miniaturization of chemical analytical methods reduces the separation time so that it is short enough, to consider the measurement equivalent to "read-time" sensing.
A second focus area is biosensing. Professor Hesketh has worked on a number of biomedical sensors projects, including microdialysis for subcutaneous sampling, glucose sensors, and DNA sensors. Magnetic beads are being investigated as a means to transport and concentrate a target at a biosensor interface in a microfluidic format, in collaboration with scientists at the CDC.
His research interests also include nanosensors, nanowire assembly by dielectrophoresis; impedance based sensors, miniature magnetic actuators; use of stereolithography for sensor packaging. He has published over sixty papers and edited fifteen books on microsensor systems.
Manufacturing, Mechanics of Materials, Bioengineering, and Micro and Nano Engineering. Advanced manufacturing and materials processing of metallic, polymeric, ceramic, and composite materials for applications in life sciences, propulsion, and energy.
Professor Das directs the Direct Digital Manufacturing Laboratory and Research Group at Georgia Tech. His research interests encompass a broad variety of interdisciplinary topics under the overall framework of advanced design, prototyping, direct digital manufacturing, and materials processing particularly to address emerging research issues in life sciences, propulsion, and energy. His ultimate objectives are to investigate the science and design of innovative processing techniques for advanced materials and to invent new manufacturing methods for fabricating devices with unprecedented functionality that can yield dramatic improvements in performance, properties and costs.