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Bioengineering Seminars for Fall 2014
Full Seminar Schedule:
Student Orientation and Introduction
Welcome - Nanyin Zhang
BMES and EGSC - Brittany Banik
Graduate Issues - William Hancock
Lab introduction - Yong Wang
Wednesday, August 27,2014, 12:10pm - 1:10pm, Room 210 Hallowell Buildin & Hershey
"Biophysical Signals and Musculoskeletal Degeneration and Regeneration"
Henry Donahue, Penn State Milton S. Hershey Medical Center
Wednesday, September 3, 2014, 12:10pm - 1:10pm, Room 210 Hallowell Buildin & Hershey
Abstract
Bone and muscle are clearly very responsive to their biophysical environment. However, the biophysical environment is too often not the focus of musculoskeletal regenerative strategies. Our laboratory is interested in exploiting the biophysical environment to prevent musculoskeletal degeneration and enhance musculoskeletal regeneration. Our work focuses on how mechanical load affects stem cell differentiation towards the osteoblastic lineage; the effect of surface energy, chemistry and topography on stem cells and how this can be translated in vivo; the mechanism underlying the bone anabolic effects of mechanical load and the catabolic effects of unloading; and the interaction of muscle and bone in response to simulated microgravity. We also have an emerging interest in 3D printing of personalized bone grafts and genomics and proteomics of bone cell mechanotransduction.
"The Materials Characterization Lab (MCL). Part of Your Team in Solving Your Problems"
Trevor Clark, Penn State Materials Research Institute
Jian Yang - Lab Introduction
Wednesday, September 10, 2014, 12:10pm - 1:10pm, Room 210 Hallowell Building & Hershey
Abstract
Last year >950 researchers from 38 departments used MCL; come find out why. We are a group of sharp problem-solvers with state-of-the-art tools. We can help you make measurements and observations right.
"Neuroimaging of Resting-State Brain Activity"
Thomas Liu, UC San Diego
Wednesday, September 17, 2014, 12:10pm - 1:10pm, Room 210 Hallowell Building & Hershey
Abstract
Modern neuroimaging methods have allowed us to study what the brain does when it is at “rest” and not engaged in an explicit task. It turns out that the “resting” brain is actually quite active and exhibits a fascinating repertoire of coordinated dynamic behavior across multiple spatial and temporal scales. In this talk, I will discuss our current understanding of resting-state brain activity and address the challenges and opportunities that lie ahead as we continue to decipher the mysteries of the “resting” brain.
"Strategies of Targeting Cancer Stem Cell: What we need?"
Jer-Tsong Hsieh, UT Southwestern
Wednesday, September 24, 2014, 12:10pm - 1:10pm, Room 210 Hallowell Building & Hershey
Abstract
Prostate cancer (PCa) often manifests as a multi-focal disease with heterogeneous cancer cells. Most studies indicate that primary PCa may derive from luminal cell or transient amplifying population based on specific cytokeratin markers such as CK8 and 18. On the other hand, castration resistant PCa (CRPC) exhibits basal cell phenotypes suggesting that CRPC may derive from cancer stem cell (CSC) capable of producing progeny cell and resisting chemo- or radiotherapy.
We have demonstrated that PCa cells with the loss of DAB2IP acquire metastatic potential, androgen-independence, and resistance to chemo-and radiotherapy. Further characterization of various DAB2IP-negative PCa cell lines indicated that these cells express different stem cell markers (such as CD117, CD44, CD24) as well as stem cell phenotypes. We have also shown the functional role of these stem cell markers in controlling stemness. Mechanistically, DAB2IP is able to regulate stemness phenotypes through unique pathways and transcriptional regulation (GATA1, ZEB1, β-catenin-TCF/LEF) of stem cell marker genes. We have validated some of these markers with clinical progression of PCa.
Based on these findings, we were able to identify key effectors in CSC. Currently, we are developing new therapeutic strategy to target CSC population by finding small molecular inhibitor(s) and natural product. From pre-clinical animal model, we have demonstrated a significant tumor inhibition by targeting CSC and its progeny population simultaneously. Furthermore, we are combining nanotechnology and molecular imaging modality to develop PCa-specific theranostic agent as a targeted therapeutic agent.
"In vivo Reprogramming for Brain Repair"
Gong Cheng, Penn State
Wednesday, October 1, 2014, 12:10pm - 1:10pm, Room 210 Hallowell Building & Hershey
Abstract
The human brain has billions of neurons and several hundreds of brain disorders have been identified. Reactive gliosis is a common pathological hallmark that is widely associated with brain injury, stroke, glioma, and neurodegenerative disorders such as Alzheimer's disease. Reactive astrocytes initially exert neuroprotective effects but later form glial scars to inhibit neuronal growth. Currently, there is no effective way to reverse glial scars back to normal neural tissue. We have recently developed an innovative in vivo reprogramming technology to directly convert reactive astrocytes into functional neurons inside the mouse brain (Guo et al., Cell Stem Cell, 2014). This is achieved through in vivo expression of a single neural transcription factor NeuroD1 in the reactive astrocytes in injured mouse brain or model animals for Alzheimer's disease. Our in vivo direct cell conversion technology will not only reduce the number of reactive astrocytes, but also generate new neurons simultaneously at the injury site for brain repair. Such internal trans-differentiation method will avoid immunorejection and cell fate uncertainty associated with conventional stem cell therapy. We have further demonstrated that cultured human astrocytes can be directly converted into functional neurons, suggesting that our in vivo cell conversion technology may be potentially developed into clinical therapies for the human brain repair.
This project was supported by grants from NIH and PSU Stem Cell Endowment Fund.
Engineering Functional Surfaces Inspired by Nature
Tak-Sing Wong, Penn State Dept. of Mechanical and Nuclear Engineering
Wednesday, October 8, 2014, 12:10pm - 1:10pm, Room 210 Hallowell Building & Hershey
Abstract
In nature, many biological surfaces are engineered to have special interfacial functions (with fluids, solids and light) in order to survive in their innate environments. The diverse functionalities exhibited by these biological surfaces are enabled by their unique surface architectures. To this end, imparting the sophisticated surface functionalities of biological surfaces into artificial materials could lead to elegant solutions to important engineering problems. In this talk, I will discuss a number of nature-inspired functional surfaces that are currently being developed in my laboratory, as well as their potential applications in the areas of energy, water, and health.
Similia similibus curantur: Bone-mimicking Composites as the New Generation of Bone Replacement Materials
Vuk Uskokovic, University of Illinois at Chicago
Wednesday, October 15, 2014, 12:10pm - 1:10pm, Room 210 Hallowell Building & Hershey
Abstract
The demand for a new generation of bone replacement materials has never been higher, given more than 2 million bone graft operations performed annually worldwide and the constant increase in this number owing to the aging population of the Earth. Despite an intense research in the field, no bone replacement material for load-bearing applications has been developed yet. The age-old principle similia similibus curantur, dictating the substitution of like with like, is expected to apply in every aspect of tissue engineering, including its bone province. Correspondingly, calcium phosphate and polymers of adequate microstructure, porosity and mechanical properties are considered as ideal candidates for achieving the functional synergy such as that occurring between nanoscopic crystals of hydroxyapatite and collagen in bone. Presented will be results on studies utilizing calcium phosphate and calcium-phosphate/polymer composites as prospective materials for bone regeneration. Examples will include the effects of morphology, topography and phase composition on an array of physicochemical and biological properties relevant for the given application. A particular emphasis will be placed on composite materials for advancing bone infection therapies. In conclusion, we will reiterate the idea that multicomponent, synergetic and multifunctional nanostructures are the most prospective types of materials for tissue engineering in general. However, in spite of the strivings towards complexity in the design of advanced materials for substitution of bone tissues, the potential of their elemental mineral component, calcium phosphate, remains largely untapped and the chemistry of this simple, yet elusive compound can be said to still conceal great treasures within.
No Seminar - BMES Conference
Wednesday, October 22, 2014
"Molecular Motors and Glioblastoma"
Steven Rosenfeld, Cleveland Clinic
Wednesday, Octoboer 29, 2014, 12:10pm - 1:10pm, Room 210 Hallowell Building & Hershey
Abstract
Glioblastoma is the most common and most malignant of primary brain tumors. The two features that define its phenotype are diffuse invasion of brain and uncontrolled proliferation. Both of these processes depend critically on the function of myosin and kinesin molecular motors, which make these enzymes potentially attractive targets for the development of new anti-invasive and anti-proliferative cancer therapeutics. My laboratory has been investigating the roles of two molecular motors that appear central to the glioma phenotype—non-muscle myosin IIA and the mitotic kinesin kif11. Our studies reveal that these motors play complex and surprising roles in driving glioma biology, and point to new directions at targeting the unregulated proliferation and dispersion that characterize these tumors.
"Plumbing the Brain"
Patrick Drew, Penn State Engineering Science and Mechanics
Wednesday, November 5, 2014, 12:10pm - 1:10pm, Room 210 Hallowell Building & Hershey
Abstract
Changes in cerebral blood flow, volume and oxygenation are widely used as indicators of neural activity, but we still have a poor understanding of how blood flow is controlled in the brain under normal physiological conditions. I will describe recent work from my lab where we use a combination of optical, electrophysiological, and quantitative techniques to understand the relationship between neural activity and the hemodynamic response. We have found that the hemodynamic response to locomotion is localized and remarkably linear. While in sensory cortex neurovascular coupling is robust, in the frontal cortex neural activity and hemodynamic signals decouple during normal behavior. Lastly, we have found that the mechanical properties of brain tissue play an important role in sculpting the vascular response.
"Equivalent Dynamic Models"
Peter C.M. Molenaar, Penn State Health Development Family Studies and Psychology
Wednesday, November 12, 2014, 12:10pm - 1:10pm, Room 210 Hallowell Building & Hershey
Abstract
Distinct forms of equivalent dynamic models are addressed. First, some powerful relations between structural equation models and state space models are highlighted, including the way in which equivalent models are defined. Next, “rotation” of linear vector autoregressive (VAR) models is discussed. An initial distinction is made between standard VARs and equivalent structural VARs. Then “rotation” of structural VARs is considered, yielding an uncountable infinitity of equivalent structural VARs. Next, a new type of equivalent VAR, called hybrid VAR, is introduced. The implications of the existence of equivalent standard VARs, structural VARs and hybrid VARs for Granger causality testing is discussed at some length. A Lagrange multiplier model search is proposed to arrive at a unique VAR representation for each given empirical data set.
"Computational Prediction of Protein Interfaces, Interactions, and Complexes"
Vasant G. Honavar, Penn State IST
Wednesday, November 19, 2014, 12:10pm - 1:10pm, Room 210 Hallowell Building & Hershey
Abstract
Protein-protein interactions are central to protein function; they constitute the physical basis for formation of complexes and pathways that carry out virtually all major cellular processes. These interactions can be relatively permanent or "obligate" (e.g., in subunits of an RNA polymerase complex) or "transient" (e.g., kinase-substrate interactions in a signaling network). Both the distortion of protein interfaces in obligate complexes and aberrant recognition in transient complexes can lead to disease. Understanding the physiological function of a protein requires knowledge of its interaction partners, the interfaces at which it binds to other proteins or small ligands, and the sequence and structural correlates of such interactions. High-throughput methods such as yeast-2-hybrid (Y2H) assays provide a source of information about possible pairwise interactions between proteins, but not the structures of the corresponding complexes. Because of the expense and effort associated with X-ray crystallography or NMR experiments to determine 3D structures of protein complexes, and the rapidly expanding gap between the number of possible interactions and the number of experimentally determined structures, there is considerable interest in computational methods for determining the structures of complexes formed by proteins. This is especially important in the case of complexes resulting from transient interactions, which tend to be partner-specific and play important roles in cellular communication and signaling pathways. This lack of information about the protein-protein structures places a significant barrier to progress in understanding the functioning of proteins as well as comprehending the topology and complexity of cellular protein interaction networks. When the structures of individual proteins are known or can be predicted with sufficiently high accuracy, docking methods can be used to predict the 3D conformation of complexes formed by two or more interacting proteins, to identify and prioritize drug targets in computational drug design, and to potentially validate interactions determined using high throughput methods such as yeast-2-hybrid (Y2H) assays.
No Seminar - Fall Break
Wednesday, November 26, 2014
"Towards Restoration of Dexterous Finger Movement using a Cortical Brain Machine Interface"
Cindy Chestek, University of Michigan
Wednesday, December 3, 2014, 12:10pm - 1:10pm, Room 210 Hallowell Building & Hershey
Abstract
Brain machine interfaces or neural prosthetics have the potential to restore movement to people with paralysis by bridging gaps in the nervous system with an artificial device. Cortical implants can record from hundreds of individual neurons in motor cortex. Machine learning techniques can be used to generate useful control signals from this neural activity. Performance can now surpass typically used EMG control signals for artificial limbs, and animals can control computer cursors with brain activity 80-105% as well as they can with their native hand. One natural next step is to attempt to control more complex movements, such as grasping. We recorded 200 channels of single unit activity in motor cortex while an animal flexed and extended his fingers. There was a significant linear correlation of (rho=0.82) between finger flexion and neural firing rates. There was also substantial information about cutaneous sensation on the fingers in primary motor cortex. Using a classifier, one can determine which of five fingers is being brushed with 68% correct. We have also recently completed a 16 channel miniaturized neural recording device to demonstrate that reduced sampling rates of 2 ksps can achieve the same decoding performance as high bandwidth systems while using 89% less power, using “spiking band” features (Stark and Abeles, 2007). In future studies, to achieve order of magnitude improvements may require an order of magnitude increase in the number of neural units recorded. Towards that end, we have recently assembled 8 um carbon threads into a 3 x 8 array, and implanted 24 fibers into motor cortex at a pitch of 150 um, successfully recording single unit activity. There is a large portion of the paralyzed community whose primary need is for finger and grasp control, which has not previously been demonstrated in a real time experiment. If high performance can be achieved, it may be possible for brain machine interfaces to become widely available for the treatment of paralysis of the hands and fingers.
"Holographic Coherent anti-Stokes Raman Scattering Imaging"
Zhiwen Liu, Penn State
Wednesday, December 10, 2014, 12:10pm - 1:10pm, Room 210 Hallowell Building & Hershey
Abstract
Holographic coherent anti-Stokes Raman scattering imaging merges the unique chemical selective capability of coherent anti-Stokes Raman scattering spectroscopy (CARS) with the amplitude and phase detection capability of holography, to result in a label-free three-dimensional (3D) imaging modality. In holographic CARS imaging, a sample is excited by a pump/probe beam and a Stokes beam to produce an anti-Stokes wide field image signal, where the frequency difference between the pump and the Stokes beams matches the molecular vibrational frequency of the sample. The coherent anti-Stokes image signal is then holographically recorded by interfering with a frequency-matched reference beam on a digital imager. The resulted digital CARS hologram captures both the amplitude and the phase of the complex anti-Stokes image field, from which 3D label-free imaging can be realized. In this presentation, we review both the off-axis and the inline digital CARS holography, as well as the application to imaging biological cells. Digital processing approaches including both digital diffractive propagation and compressive sensing based methods are also discussed.
For additional information, contact Ms. Doretta Garvey, Department of Biomedical Engineering, Tel: 814.865.1407 or E-Mail: bioe@engr.psu.edu