Biomedical Modeling Research Overview

Benveniste, Helene

Chair, Medical Department

Benveniste@bnl.gov

Summary : Benveniste's Laboratory focuses on (1) exploring, characterizing and understanding diagnostic MR contrast parameters suitable to visualize neuro-pathology in neurodegenerative diseases; (2) investigate transgenic animal models were specific genes are modified to understand mechanism(s) and treatment of addiction and of drug-induced neurotoxicity using high resolution MR imaging, (3) advance technologies in molecular MR imaging.

Bluestein, Danny

Professor

Danny.Bluestein@sunysb.edu

Summary : Despite major progress, cardiovascular diseases remain the leading cause of death in the western world. One of the major culprits in cardiovascular disease and in devices designed to treat or restore impaired cardiovascular function is the non-physiologic flow pattern that enhances the hemostatic response mainly through platelet activation. Platelets have long been regarded as the preeminent cell involved in physiologic hemostasis and pathologic thrombosis. An innovative technique for measuring flow induced platelet activation has been developed, and its utility demonstrated in experiments conducted in recirculation devices (models of arterial stenosis, Left Ventricular Assist Device (LVAD), and mechanical heart valves). The mechanisms by which the non-physiologic flow patterns induce platelet activation and generate free emboli, that enhance the risk of cardioembolic stroke, was demonstrated in vivo with mechanical heart valves implanted in the sheep model. The results of this research will aid in elucidating physical forces that regulate cellular function in flowing blood, and may be applied to improve the design of blood recirculating devices and to develop more potent drugs for treating cardiovascular diseases.

Chon, Ki

Professor

Ki.Chon@sunysb.edu

Summary : The cardiac autonomic nervous system is responsible for maintaining proper homeostasis, or balance, of the cardiovascular system. One of our major areas of research is to detect, quantify, and interpret differences in dynamic characteristics of the cardiac autonomic nervous system between normal and diseased subjects, in an attempt to find a marker for increased risk of sudden cardiac death. Identifying and quantifying differences in the dynamic characteristics of autonomic function between normal and diseased conditions may lead to a better understanding of the role of autonomic function imbalance in diseased conditions, and should have important clinical diagnostic and prognostic applications. Another active research area is the development of computational modeling approaches to understand differences in dynamics of renal autoregulatory mechanisms between normotensive and hypertensive conditions. For both areas of research, we are developing novel linear and nonlinear signal processing techniques that can be successfully applied to achieve the research objectives.

Einav, Shmuel

Professor

seinav@sunysb.edu

Summary : The primary role of this laboratory is to study basic physiological flow phenomena, both experimentally and numerically, as well as cellular and tissue engineering as applied to the vascular system. and to suggest ways of improving the functioning of cells, tissues and organs in the body. These physiological flows include blood flow in the heart, blood flow in arteries, veins and the microcirculation, air flow in the respiratory airways, and urine flow in the kidney and urethra. This laboratory simulates systems through the use of computers, assisting life scientists to better understand physiological functions without having to rely entirely on living systems as experimental models. The use of mathematical analysis helps minimize animal experimentation. Other projects are the investigation of hemodynamics as a regulator of vascular biology, the mathematical modeling of the dynamic response of mammalian cells, the role of flow and the associated shear stress on vascular endothelial biology, prosthetic circulatory devices and the tissue engineering of blood vessel substitutes. The laboratory is also engaged in the evaluation of critical conditions that lead to failure of biological organs, such as the heart and the coronary circulation, failure of circulatory prosthetic devices as stents, heart valves and grafts. To facilitate in vitro and in vivo studies, the laboratory develops new investigative techniques, noninvasive diagnostic methods, and advance, multi-dimensional numerical modeling.

Entcheva, Emilia

Associate Professor

Emilia.Entcheva@sunysb.edu

Summary : The focus of the Cardiac Cell Engineering Laboratory is designing and characterizing heart cell networks and heart tissue in the lab to gain a better understanding of how cardiac cells self-organize and function. We are motivated to provide useful tools for physiomics type of studies, drug, gene and stem cell therapy testing 3D cellular platforms - an experimental setting for validation of computer models of excitable tissue, and ultimately to contribute to strategies for the regeneration of the heart. This research is multidisciplinary in nature and involves a spectrum of experimental molecular and cell biology procedures, along with the application of design concepts from electrical, optical, mechanical and chemical engineering to create the enabling technology for our studies. New imaging modalities, image processing algorithms and computer modeling are essential complementary tools developed and applied by our team. Key research areas include: 1) optical mapping of excitation; 2) advanced signal and imageprocessing; 3) cardiac cell and tissue engineering; 4) unraveling the mechanisms of cardiac arrhythmias.

Judex, Stefan

Associate Professor

Stefan.Judex@sunysb.edu

Summary : Research in this laboratory focuses on the identification of precise parameters that define skeletal tissue quantity and quality and their perturbation to applied physical stimuli. To this end, state of the art imaging techniques (e.g., microCT or synchrotron infrared spectroscopy) are combined with molecular (e.g., RT-PCR), genetic (e.g., QTL), and engineering techniques (e.g., finite element modeling) to determine genes, molecules, forces, as well as chemical and structural matrix properties. An example for a recent study includes the demonstration that extremely small amplitude oscillatory motions (~ 100µm), inducing negligible deformation in the matrix, can serve as an anabolic stimulus to osteoblasts in vivo, producing a structure that is mechanical stronger and more efficient to withstand forces. Recent results also indicate that there is not only a genetic basis for bone architecture, but also that the sensitivity of bone tissue to both anabolic and catabolic stimuli is influenced by subtle genetic variations. The identification of the specific chromosomal regions that modulate this differential sensitivity is in progress. Clinically, our studies may lead to the development of effective prophylaxes and interventions for osteoporosis, without side-effects and tailored towards the genetic make-up of an individual.

Kaufman, Arie E.

Professor

Arie.Kaufman@sunysb.edu

Summary : Arie Kaufman is the director of the Center of Visual Computing (CVC) and the director of the Cube project for volume visualization supported by the National Science Foundation, Department of Energy, Office of Naval Research, Hughes Aircraft Company, Hewlett-Packard Company, Silicon Graphics Company, Howard Hughes Medical Institute, and many others. His research interests include computer graphics and specifically computer graphics architectures, algorithms, and languages; visualization including volume visualization and scientific visualization; user interfaces; virtual reality; and multimedia. Kaufman is the editor-in-chief of the IEEE Transaction on Visualization and Computer Graphics. He has lectured widely and published numerous technical papers in these areas, including the IEEE tutorial book on Volume Visualization. He has been the papers chair and program cochair for Visualization 1990-1994 and the chairman of the IEEE CS Technical Committee on Computer Graphics.

Mueller, Klaus

mueller@cs.sunysb.edu

Summary : Klaus Mueller's areas of interest are medical, scientific and information visualization, visual analytics, medical imaging, computer graphics, virtual and augmented reality, and high-performance computing. He has pioneered the use of programmable commodity graphics hardware boards (GPUs) for the acceleration of a wide variety of computer tomographic (CT) reconstruction algorithms and medical physics phenomena. Applications include diagnostic imaging, radiotherapy, electron microscopy, ultrasound tomography for breast mammography, and others. In the visual analytics area he works on devising new high-dimensional data visualization frameworks and combining them with statistical pattern recognition and machine learning to create intuitive interactive analytical reasoning environments for medical professionals. He is also working towards a comprehensive visual data mining environment for neuroscientists, called BrainMiner, to enable a more targeted and experiential derivation of brain functional models from large collections of knowledge and data.

Qin, Yi-Xian

Professor

Yi-Xian.Qin@sunysb.edu

Summary : Early diagnostic of osteoporosis allows for accurate prediction of fracture risk and effective options for early treatment of the bone disease. A new ultrasound technology, based on focused transmission and reception of the acoustic signal, has been developed by Dr. Qin and his team which represents the early stages of development of a unique diagnostic tool for the measure of both bone quantity (density) and quality (strength). These data show a strong correlation between non-invasive ultrasonic prediction and micro-CT determined bone mineral density (r>0.9), and significant correlation between ultrasound and bone stiffness (r>0.8). Considering the ease of use, the non-invasive, non-radiation based signal, and the accuracy of the device, this work opens an entirely new avenue for the early diagnosis of metabolic bone diseases.

Rubin, Clinton

Distinguished Professor & Chair

Clinton.Rubin@sunysb.edu

Summary : Encouraging results show that the application of extremely low level strains to animals and humans will increase bone formation, and thus may represent the much sought after "anabolic" stimulus in bone. More than 15 years of research into non-invasive, non-pharmacological intervention to control osteoporosis, was referenced in Dr. Rubin's paper published in the journal Nature (August 9, 2001; 412:603-604). Dr. Rubin's studies suggest that gentle vibrations on a regular basis will help strengthen the bones in osteoporosis sufferers and increase bone formation. In his study, adult female sheep treated with gentle vibration to their hind legs for 20 minutes daily showed almost 35% more bone density. Clinical trials have been completed on post-menopausal women, children with cerebral palsy, and young women with osteoporosis, all with encouraging results. In expanding the research platform into other physiologic systems, current work demonstrates that these low-level signals influence mesenchymal stem cell differentiation, such that their path to adipocytes is suppressed, and markedly reduces adipose tissue.

Strey, Helmut

Associate Professor & Graduate Program Director

Helmut.Strey@sunysb.edu

Summary : Nature's ability to assemble simple molecular building blocks into highly ordered materials, such as those found in cell membranes, cell nuclei, cytoskeleton, cartilage, or bone presents many fascinating and unanswered questions. We are interested in how to tune the interactions of water-soluble building blocks so as to induce their self-assembly into useful microstructures much needed for the next generation of controlled drug delivery, biosensors and DNA sequencing applications. In particular, we are working on long-range ordered polyelectrolyte-surfactant microemulsions that are used as templates for solid nanoporous materials using polymerization and/or cross-linking strategies. Such materials, because of their well-ordered porous structure, will allow more efficient molecular separation and drug delivery. In addition, we are developing biosensors that are based on biopolymer chiral liquid crystals and quantum dot colloidal crystals. In both cases the softness of the systems allows the induction of a strong optical response to external stimuli. Such sensors should be able to quantitatively detect and measure analyte concentrations at hormonal levels.

Vaska, Paul

Associate Scientist

vaska@bnl.gov

Summary : The research interests of Dr. Vaska comprise all aspects of the physics of positron emission tomography (PET). This ranges from the development of unique detector technologies which extend the limits of spatial resolution and sensitivity, through improved corrections for physical effects, image reconstruction methods, and post-processing techniques to improve image quantitation. He has worked extensively with both human and small-animal PET systems and oversees the physics aspects of the clinical PET research carried out at the BNL PET facility. His previous research as a physicist for a major PET firm included development of a dedicated brain scanner in collaboration with the University of Pennsylvania, and novel calibration and data acquisition methods. A recent advance in the field of neuroimmunomodulation was our identification of the “cholinergic anti-inflammatory pathway,” a neural-immune connection through which the central nervous system inhibits systemic inflammation. It had been widely known that TNF, IL-1 and other mediators interact with the vagus nerve in the periphery, and induce afferent signals to the brain; the brain, in turn, responds with anti-inflammatory signals mediated by steroids such as ACTH and MSH. We discovered that the brain also utilizes conventional neurotransmitters that are released from the vagus nerve to generate a response in peripheral organs. In vivo, surgical vagotomy prevents this communication; animals exposed to endotoxin succumb to endotoxic shock more rapidly than animals with an intact vagus. We also found that macrophages express acetylcholine receptor activity, and that acetylcholine can block the activation of macrophages in response to endotoxin. Electrical stimulation of the vagus nerve inhibits systemic inflammation, inhibits the release of TNF, HMG-1, and other mediators, and prevents death due to endotoxic shock. Ongoing studies are focused on identifying the neural substrate of this system, developing optimal stimulation parameters, and determining the molecular basis of cholinergic signal transduction in macrophages.

Wang, Yi

MR Physicist

Yi.Wang@chsli.edu

Summary : The Cardiac MRI research lab in St. Francis Hospital focuses on noninvasive in vivo cardiovascular imaging for the heart functional and morphological assessment using magnetic resonance imaging and image processing techniques. My current major research interests are: Tissue contrast, artifact suppression and MRI sequence design related to fast cardiac imaging, Myocardium perfusion on ischemic heart, Cardiac vessel imaging to evaluate coronary artery stenosis and atherosclerotic plaque.

Zhang, Michael Q.

Associate Professor

mzhang@cshl.edu

Summary : The long-term goal of research in our lab is to use mathematical and statistical methods to identify functional elements in eucaryotic genomes, especially the genes and their control and regulatory elements. A genome is the program book of a life, genome research will lead to eventual decoding of the entire genetic language of life and its grammar. Driven by the Human Genome Projetc, our current interest is on two related problems: gene-finding and gene expression analysis. Since most of eukaryotic genes are split by intervening sequences (called introns), after transcription of a gene into a precursor mRNA, the introns have to be spliced out and the remaining fragments (called exons) have to be joined together as a mature mRNA before it can be translated into protein. Therefore, the key of gene-finding is to identify these exons. Constitutive coding exons are relatively easy to identify, the greatest challenge lies in the identification of end exons and alternatively spliced exons. Since this requires the study of many important control and regulatory elements for gene expression. This link between gene structure and function at the genomic level requires high-throughput functional studies. Detecting cis regulatory elements and modeling gene expression networks are becoming new challenges in the functional genomics era. Working closely with bench-scientists, our investigation will undoubtedly contribute to the understanding of genome organization as well as their control and regulation mechanisms, which will in turn have a profound impact on biology and medicine.