Biomechanics and mechanobiology of cell adhesion and signaling molecules of the immune system and the vascular systems:
Our interests lie in the adhesion and signaling molecules of the immune system as well as those involved in platelet adhesion and aggregation. We are primarily focused on early cell surface interaction kinetics and their primary signaling responses, as these are critical in determining how a cell will ultimately respond upon contact with another cell. The majority of our work ranges from single molecule interaction studies using atomic force microscopy, molecular dynamics simulations, or biomembrane force probe assays to single cell studies using micropipette adhesions assays, fluorescence imaging techniques, or real-time confocal microscopy. These assays focus on the mechanics and kinetics of receptor-ligand binding and their downstream signaling effects within cells. T cell receptors, selectins, integrins, and their respective ligands are some of the cell surface molecules currently under investigation in our lab. Understanding the initial interaction between molecules such as these and their subsequent early signaling processes is crucial to elucidating the response mechanisms of these physiological systems. Ultimately, our research strives to help better understand the mechanisms within these systems for possible medical applications in autoimmunity, allergy, transplant rejection, and thrombotic disorders.
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.
Bio-inspired colloidal assembly for multifunctional drug delivery vehicles and colloidal-based sensing.
Dr. Milam’s current research interests focus on designing and characterizing colloids functionalized with biologically-relevant macromolecules such as oligonucleotides and cellular adhesion molecules. The specific recognition between matching macromolecules such as complementary DNA strand pairs allows for programmable adhesion between either complementary particle surfaces or between complementary particle and matrix interfaces. Using a variety of biocompatible and biodegradable materials as the colloidal substrate, these biocolloids will serve as building blocks to fabricate novel material constructs ranging from stimuli-responsive hybrid materials to therapeutic delivery vehicles.
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.
Neuroscience, neural engineering, human augmentation, human-robot interaction, rehabilitation, sport science
Physiological and biomechanical mechanisms underlying fine motor skills and their adjustments and adaptations to heightened sympathetic nerve activity, aging or inactivity, space flight or microgravity, neuromuscular fatigue, divided attention, and practice in humans. He uses state-of-the-art techniques in neuroscience, physiology, and biomechanics (e.g., TMS, EEG, fMRI, single motor unit recordings, microneurography, mechanomyography, ultrasound elastography, and exoskeleton robot) in identifying these mechanisms.
Using yeast Saccharomyces cerevisiae as a model, my laboratory investigates molecular mechanisms underlying eukaryotic genome stability. Chromosomal rearrangements create genetic variation that can have deleterious or advantageous consequences. Karyotypic abnormalities are a hallmark of many tumors and hereditary diseases in humans. Chromosome rearrangements can also be a part of the programmed genetic modifications during cellular differentiation and development. In addition, gross DNA rearrangements play a major role in chromosome evolution of eukaryotic organisms. Therefore, elucidation of molecular mechanisms leading to chromosome instability is important for studying the human pathology and also for our understanding of the fundamental processes that determine the architecture and dynamics of eukaryotic genomes.
My overall contribution to the field of genome instability has been the demonstration of the phenomenon that repeats often found in higher eukaryotic genomes including the human genome are potent sources of double-strand breaks (DSB) and gross chromosomal rearrangements (GCR). Specifically, my lab, is investigating how repetitive sequences that can adopt non-B DNA secondary structures pose a threat to chromosomal integrity dictated by their size and arrangement. Currently three sequence motifs are studied in my laboratory: inverted repeats; Friedreich’s ataxia GAA/TTC trinucleotide repeats and G-quadruplex-forming tracts. We also are collaborating with Dr. Malkova lab, University of Iowa, to study one of the outcomes of the DSB formation at unstable repeats – break-induced replication.
Dr. Serban's research interests on Health Analytics span various dimensions including large-scale data representation with a focus on processing patient-level health information into data features dictated by various considerations, such as data-generation process and data sparsity; machine learning and statistical modeling to acquire knowledge from a compilation of health-related datasets with a focus on geographic and temporal variations; and integration of statistical estimates into informed decision making in healthcare delivery and into managing the complexity of the healthcare system.
Research in our laboratory focuses on a class of intracellular ion channels know as ryanodine receptors (RyRs). In mammals, there are three RyR isoforms. RyR1 and RyR2 are the predominate isoforms in skeletal and cardiac muscle, respectively where they are the primary efflux pathway for the release of calcium from the sarcoplasmic reticulum to activate contraction. RyR3 has a wide tissue distribution and contributes to calcium regulation in a variety of cell types. RyRs are the largest known ion channel and are regulated by a multitude of endogenous effectors, including ions, metabolites and regulatory proteins. Therefore, an area of interest is the regulation of these RyR channels by endogenous effectors; especially as it relates to altered contractile function associated with cardiac and skeletal disease, skeletal muscle fatigue and aging. We analyze channel function on multiples levels of organization. Sarcoplasmic reticulum vesicle [3H]ryanodine binding is used to examine large populations of channels. Individual channels are incorporated into artificial lipid bilayers in order to record single channel currents and assess channel kinetics. Calcium release from permeabilized muscle fibers provides a method of examining RyR function in situ. My research has two long-range goals. The first is to understand how intracellular calcium is regulated and how alterations in the regulation effects cell function. The second goal is to understand the RyR regulatory sites that could potentially be exploited for the development of pharmacological compounds to treat disorders of cellular calcium regulation.
Modelling and controlling metabolic dynamics and regulation (metabolic engineering)
Systems biology-based experimental and bioinformatics analysis of metabolism
Synthetic biology for the development of biosensors and diagnostics
The main focus of the Styczynski group is the experimental and computational study of the dynamics and regulation of metabolism, with ultimate applications in metabolic engineering, biotechnology, and biosensors/diagnostics.