115 C Laufer Center
Henry Laufer Endowed Associate Professor
Summary : The goal of my laboratory is to develop synthetic gene circuits (small constructs built from genes and their regulatory regions), and use them for biological discovery and practical applications (such as therapeutic gene expression control). For example, using synthetic gene circuits in yeast cells, we could demonstrate that noise (nongenetic cellular diversity) can aid microbial survival during antibiotic treatment and thereby enable the development of drug resistance. We have designed "linearizer" gene circuits in yeast cells that can tune a protein's level precisely, such that the protein concentration is proportional to an extracellular inducer and uniform within a cell population. We have moved this synthetic gene circuit into mammalian cells and can now tune the expression of a cancer-related genes precisely, to investigate how the level of tumor progression-related proteins affects invasion, migration and other metastasis-related cell behaviors. In the future, similar gene circuits may enable novel approaches to gene therapy. Our research is inherently interdisciplinary, since we use mathematical and computational models in combination with single-cell level measurements to characterize the dynamics of synthetic and natural gene networks, and to understand the cellular and multicellular behaviors they confer.
Health Sciences Center Level 15, Room 090
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.
Bioengineering Building, Room G05
Research Assistant Professor
Summary : Our goal is to better describe and understand the role of tissue heterogeneity in normal tissues and in the onset and development of diseases like cancer. Most tissues are comprised of a complex mixture of different cell types, and even cells within a clonal population exhibit a high degree of heterogeneity. However, the detailed behavior of individual cells is obscured in typical measurements which are averaged over cell populations. As a result, it has been difficult to comprehend the functional relevance of this heterogeneity due to the lack of adequate techniques. In order to enable the analysis of tissue heterogeneity we are developing an experimental approach based on droplet microfluidics that allows the manipulation of single cells by suspending them in drops carried in an inert fluid. These drops can then be automatically combined with reaction solutions, interrogated with fluorescent dyes or sorted to carry out sample preparation and analysis. My research exploits the advantages conferred by droplet microfluidics over conventional technologies and other microfluidics techniques in terms of automation, throughput and combinatorial power for the manipulation and analysis of single-cells.
Health Sciences Center Level 16, Room 60
Summary : Our laboratory focuses on the design and development of bioactive peptides and 3-D complex extracellular matrices (ECM) that will enhance soft tissue repair and regeneration. Peptides are assayed for biologic activity in vitro and in vivo for their ability to protect tissue cells and organs from injury, stimulate tissue cell migration and proliferation, and modulate stem cell and tissue cell differentiation. The ECM constructs tethered with bioactive peptides are analyzed for their physical, chemical and immunologic properties by such modalities as goniometry for hydrophilicity, static and dynamic stress and strain for viscolastic material properties, atomic force microscopy for Young’s elastic moduli and surface topography; HPLC, mass spectroscopy, gel permeation chromatography and gel electrophoresis for chemical analysis; and fluorescence immunoassays for immunologic epitope mapping. In addition, cell interactions with the 3-D ECM constructs are examined at the transcriptional, protein and functional level as judged by real-time PCR, DNA microarray analyses, Western blots, proteomics, quantitative fluorescence microscopy, and cell viability, migration and proliferation assays. Special in vitro systems have been created to quantify sprout angiogenesis, epithelial sheet migration and neurite axon extension. Bioactive peptides and engineered ECM containing peptide biomimetics will also be tested in a variety of animal models and hopefully enter into clinical trials. This robust array of bioactive peptides and 3-D ECM constructs will provide new therapies for soft tissue injury and disease.
Life Science Building, room 002
Associate Professor and Scientist
Summary : The broad goal of this laboratory is to develop advanced optical instrumentation to detect and characterize the physiological processes in the living biological systems such as brain and heart. More specifically, cutting-edge optical spectroscopy and imaging techniques are developed that permit simultaneous detection of cerebral blood flow, blood volume and tissue oxygenation, as well as intracellular calcium in vivo. We are interested in studying drug-induced abnormalities of the brain function. Cocaine is chosen as one of the preliminary drugs for our research applications because it affects cerebral hemodynamcs, metabolism, and neuronal activities in the brain. The mechanisms that underlie cocaine’s neurotoxic effects are not fully understood, partially due to the technical limitations of current neuroimage techniques to differentiate cerebrovascular from neuronal effects at sufficiently high temporal and spatial resolutions. To solve this problem, we have developed a multimodal imaging platform that combines multi-wavelength laser speckle imaging, optical coherence tomography, and calcium fluorescence imaging to enable simultaneous detection of cortical hemodynamics, cerebral metabolism, and neuronal activities of animal brain in vivo, as well as its integration with microprobes for imaging neuronal function in deep brain regions in vivo. Promising results of in vivo animal brain functional studies demonstrate the potential of this novel multimodality approach to compliment other neuroimaging modalities (e.g., PET, fMRI) for investigating brain functional changes such as those induced by drugs of abuse.
Institute for Molecular Cardiology, BST-6, Rm. 120B
Summary : The Cardiac Optogenetics & Optical Imaging Laboratory develops new optical modalities for actuation and sensing of the electromechanical function in cardiac cells and tissues. Our lab leads pioneering work in the field of cardiac optogenetics - the use of light for the precise interrogation, stimulation and control of excitable tissue, including heart, that has been genetically altered to become light-sensitive. We develop useful tools for physiomics type of studies, drug, gene and stem cell therapy testing 3D cellular platforms, also needed for experimental validation of computer models of excitable tissue. 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) cardiac optogenetics; 2) optical mapping of excitation; 3) advanced signal and image processing; 4) cardiac cell and tissue engineering; 5) unraveling the mechanisms of cardiac arrhythmias.
Bioengineering Building - G19
Associate Professor & Undergraduate Program Director
Summary : " Our emerging understanding of oxygen delivery to the tissues is that the blood flow within the smallest arterioles is tightly organized within repeating networks across the tissue. Central to this new paradigm are the concepts of vascular communication between the beginning and end of the network (via gap junctions), and its relation to flow sensing by the vascular endothelium. Our work has shown that different types of microvascular flow patterns can be triggered by direct stimulation of the focal adhesions (alpha-v-beta-3 integrins, i.e., wound healing), compared to adenosine (i.e., metabolic change), compared to nitric oxide (i.e., inflammation), hence we can control the flow patterns. Among the goals of this work are in vitro construction of transplantable microvascular networks, using bionanotechnology to create the sturdy scaffolding, and verification of nanofabricated drug delivery units within the vasculature. To this end, equally important are mechanotransduction of the physical forces associated with flow change (i.e., wall shear stress), the pharmacologic signal transduction systems involved (which guide drug discovery and intervention), and the molecular basis for the committed step that ensures healthy flow delivery. Our work employs computational modeling of the fluid mechanics, the physiology of arteriolar network blood flow (in vivo and in vitro), and precise genomic manipulation of key proteins in healthy and vascular disease states. "
Bioengineering Building - Room 213
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.
Bioengineering Building - Room G09
Summary : Research in our lab focuses on the embedded systems and high performance computing technologies in biomedical applications. Research projects have covered a vast range from the wearable wireless infant monitor for the prevention of sudden infant death syndrome to ultrasound scanning imaging device for the assessment of bone properties. We adopted the latest technologies in embedded system design and established own platforms for the medical device prototyping to facilitate the transition of intellectual properties from bench side to bed side. We are capable of building miniaturized medical devices using microcontroller based design and integrating large sophisticated devices using off shelf components. We specialize in FPGA technology for our HPC research project because it offers the flexibility of hardware configuration that also benefits the data acquisition and control aspects in the projects.
Bioengineering Building, G-15
Summary : Our laboratory develops biomedical optical devices for diagnostics and therapy. Examples include miniature microscopes for real-time optical biopsy of living tissues, as well as spectral imaging devices for in vivo molecular screening of disease biomarkers. Our projects are multi-disciplinary and collaborative, involving the development of advanced optical instrumentation, the use of molecularly-targeted contrast agents, the validation of technologies with preclinical animal models and tissue culture, as well as the translation of devices into the clinic.
Bioengineering Building - Room 119
Summary : Dr. Mujica-Parodi is Director of the Laboratory for Computational Neurodiagnostics (LCNeuro). LCNeuro obtains neural signals non-invasively through imaging by functional MRI, near-infrared spectroscopy, and electroencephalography. The complexity or chaotic features of these neural time-series are then quantified using a variety of computational techniques adapted from physics, such as power spectrum scale invariance, detrended fluctuation analysis, Hurst and Lyaponov exponents, and approximate entropy. Deviations from the critical degree of chaos are used diagnostically in conjunction with classification algorithms, to identify risk for illness even before a system has degenerated sufficiently to show onset of symptoms. Application of graph theory and dynamic causal modeling permits identification of the circuit-wide basis for this dysregulation, which in turn is used for developing treatment targeted to these specific circuits.
Bioengineering Building - Room G17
Summary : 2D and 3D cross-sectional optical imaging of biological tissue at close to cellular resolution (e.g., 10um) and at depths of 1-3mm can have significant impacts on noninvasive or minimally invasive clinical diagnosis of tissue abnormalities, e.g., tumorigenesis. Laser scanning endoscopes, based on optical coherence tomography (OCT), have been developed and tested on a wide variety of tissues both ex vivo and in vivo. Encouraging results based on animal and human studies show that LSE can provide morphological details correlated well with excisional histology, suggesting its potential for optical biopsy or optically guided biopsy to reduced negative biopsies in clinical practice. Current research of Dr. Pan’s lab is focused on early-stage epithelial cancer detection, diagnosis of cartilage injury and healing, and assessment of engineering tissue growth. In addition, Dr. Pan’s lab studies skin dehydration, geriatric incontinence and laser/biochemical attack to the eye using OCT and light microscopy.
Bioengineering Building - Room 215
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.
Bioengineering Building – Room 101
Summary : The goal of our lab is to 1) develop a biomimetic three-dimensional tissue engineering scaffolds that promotes microvascular blood vessel growth and 2) elucidate mechanisms that induce cardiovascular disease responses. The need for new tissue engineering scaffolds that promote microvascular growth arises due to diffusion limitations through biological tissue, which at best is approximately 100 microns. With a method to fabricate patent vascular networks ex vivo, it is possible that large scale tissue engineering applications can be realized or the healing of chronic wounds can be accelerated. Our work has identified a number of viable scaffolds that can promote vascular network growth. Additionally, more recent work has focused on identifying scaffold fabrication techniques that can form viable scaffolds for microvascular applications. Cardiovascular diseases remain the leading cause of death in the Western world. Due to this, it is salient that an understanding of disease progression is found. We aim to understand how combinations of cardiovascular disease risk factors interact to induce, accelerate, enhance or inhibit cardiovascular disease processes. Our main focus is on advanced glycation end products (diabetes), tobacco smoke and disturbed wall shear stress. We focus on platelets, endothelial cells and their interactions for all projects in our lab.
Bioengineering Building - Room 217A
Distinguished Professor & Chair
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.
Bioengineering Building - Room 115
Summary : Our laboratory seeks to integrate advances in nanoscience and technology with the biological sciences and clinical medicine to achieve significant advances in simultaneous molecular diagnostics and therapeutics (theragnosis), drug delivery, and bioengineering. Towards these ends, our research interests involve a multidisciplinary approach for the development of functional (electronic, optical, magnetic, or structural) bionanosystems as contrast agents for molecular imaging, as carriers for drug delivery, and as structural scaffolds for tissue engineering. Our current projects capitalize on the unique properties of carbon nanobiomaterials to develop a) advanced contrast agents (CAs) for molecular magnetic resonance imaging (MRI), b) nanocomposites to improve the physical and biological (osteoconduction and osteoinduction) properties of polymer scaffolds for bone tissue engineering and c) non-viral vectors for gene transfection. We have exploited the potential of Gd-based carbon nanostructures: Gd@C60 metallofullerenes (gadofullerenes) and Gd@Ultrashort-tubes (gadonanotubes) as a new generation of advanced CAs for MRI and shown them to have efficacies up to 100 times greater than current clinical CAs. Our recent studies show that they are particularly well suited for passive (magnetic labels for cellular MRI) and active (pH sensitive probes for cancer detection) MRI-based Molecular Imaging. Single-walled carbon nanotubes (SWNTs) have been proposed as the ideal foundation for the next generation of materials due to their excellent mechanical properties. We have dispersed SWNTs and ultra short SWNTs into fumarate-based polymers to form nanocomposite scaffolds that exhibit mechanical properties far superior to the polymers alone and are osteoconductive as well osteoinductive. Our research work involves material synthesis techniques, physico-chemical characterization techniques, tissue culture and in vivo studies.
Bioengineering Building - Room G13
Associate Professor & Graduate Program Director
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.
Professor and Scientist
Summary : Medical imaging techniques have undergone substantial growth in recent years, in both the research and clinical arenas. The standard anatomical imaging modalities of computed tomography (CT) and magnetic resonance imaging (MRI) have been complemented by quantitative functional approaches like positron emission tomography (PET) and single photon emission computed tomography (SPECT). Our lab develops new instrumentation and processing techniques not only to enhance the functional capabilities of PET, but also to combine it with synergistic modalities such as MRI to provide unprecedented, multidimensional information for cancer diagnosis, brain research, and many other applications. We have developed a miniaturized brain scanner for rodents (RatCAP) which avoids the potentially confounding effects of general anesthesia in rat brain studies, and even allows for the simultaneous study of behavior along with neurochemistry by PET. We have also developed new approaches for very high spatial resolution in PET, including a solid-state imager using cadmium zinc telluride (CZT) which achieves sub-mm resolution, and a monolithic scintillator detector with depth-encoding capability via a novel maximum likelihood positioning algorithm. And we have developed multiple imaging systems for simultaneous imaging with PET and high-field MRI, including a rodent brain scanner, a whole-body rodent system, and a prototype clinical breast imager. The research encompasses the development of new detector materials and concepts, low-noise microelectronic signal processing, high-throughput data acquisition methods, Monte Carlo simulation, and new data processing techniques to optimize the extraction of quantitative information from the PET data.
Bioengineering building 109
Summary : Cardiovascular disease is the leading cause of death in the United Sates, and coronary artery disease is the most common type of cardiovascular disease. Shear stress induced by blood flow plays an important role in the initiation and development of atherosclerosis, the major reason for coronary artery disease. Circulating platelets and vascular endothelial cells are very sensitive to their mechanical environment; any change can affect their functions and interactions significantly. My major research interest is to investigate how altered blood flow and stress distribution affect platelet and endothelial cell behavior and lead to cardiovascular disease initiation. Computational fluid dynamics modeling, along with in vitro and ex vivo experiments, are carried out to study platelet and endothelial cell responses under physiologically relevant dynamic conditions. Biomarkers associated with platelet and endothelial cell activation are of special interest to us. We also work on numerical models to describe platelet coagulation kinetics and platelet adhesion to injured blood vessel wall under dynamic flow conditions.