Buffalo Blue Sky Funded Projects

33 approved project(s) found.
Title
Submitted by
Date
2019-08-07

Coin holders:

Sonodynamic therapy (SDT) is an emerging approach for eradication of tumors, which involves a combination of low-intensity ultrasound and specialized drugs known as sonosensitizers. In response to sonoluminescence, generated by cavitation of the surrounding liquid medium upon ultrasound activation, sonosensitizers produce cytotoxic reactive oxygen species (ROS) that can effectively destroy cancer cells. The deep penetration of ultrasound enables treatment of deep-seated tumors. Despite its breakthrough potential, SDT is still at a very early stage of development and the mechanisms of ROS generation by ultrasound are poorly understood. Furthermore, production of ROS within large tumors is ineffective because of the hypoxic environment. This proposal will address the current limitations of SDT and support the development of efficient nanocarrier based approaches. In order to move our multidisciplinary team into this new area, in which we have not previously published work, we propose the following specific aims: Specific Aim 1: Characterization of the mechanisms of SDT via multi-scale modeling and characterization of ROS production in biological microenvironment. We will study the formation of shock waves within collapsing gas bubbles in different biological media to quantify the excitation efficiency of sonosensitizers, using both computational and experimental approaches. We hypothesize that ROS production levels may vary depending on protein concentration, viscosity, pH, and other factors in the tumor environment. Specific Aim 2: Development of nanocariers to deliver sonosensitizers and oxygen to the tumors to affect SDT. We will produce nanoemulsions containing both sonosensitizers and oxygen-releasing agents to affect efficient SDT in hypoxic tumor environments. Specific Aim 3: Validation of a novel SDT platform in cell culture models. We will validate and optimize SDT to induce apoptosis in cultured cells, comparing it to conventional photodynamic therapy.

2019-08-07

Coin holders:

New Faculty:

winchen

Design of human-computer interfacing has focused heavily on the form of visual feedback provided to users that they may use to voluntarily control actions. Only in the last decade have concerted attempts been made to tap directly into internal signals, such as electrophysiological response patterns, to provide instructions or feedback to computers. We will use ambulatory sensors to record physiological measures of heart-rate, heart-rate variability, electrodermal activity, thermodermal activity, fNIR measurements, and motoric variability while participants perform complex cognitive and sensorimotor tasks using digital feedback to develop new biomarkers predictive of increasing cognitive load and decreasing cognitive plasticity. Aim 1 will be to quantitatively characterize individual differences in physiological responses that are correlated with fluctuations in vigilance and performance accuracy in a simulated driving task. Aim 2 will be to test whether identified biomarkers are also predictive of user performance on an unrelated cognitive task requiring the entry and tracking of detailed medical status information. Empirically-driven customization of human-computer interfaces based on physiological profiles of users can potentially increase usability of existing systems and speed learning of new systems.

2019-07-08

Coin holders:

Lithium belongs to a class of kinase-targeting therapies, including the diabetes medication exenatide and the cancer medication nilotinib, that have demonstrated promise as disease-modifying therapies for Parkinson’s disease (PD). Lithium targets protein kinase B (Akt) and glycogen synthase kinase-3 beta (GSK-3B, a downstream target of Akt) in manners that recapitulate those of exenatide and nilotinib. Also, lithium inhibits inositol monophosphate leading to enhanced autophagy and reduced intracellular levels of alpha-synuclein, which is believed to be a primary mediator of the progressive neurodegeneration in PD and is significantly 78x higher in the plasma of PD patients compared to healthy controls. The transcriptional cofactor B-catenin mediates the transcription of neuronal survival genes implicated in PD such as nuclear receptor related 1 (Nurr1), which is significantly reduced by 61% in PD peripheral blood mononuclear cells (PBMCs). Through its ability to inhibit GSK-3B, lithium can enhance B-catenin-mediated activity and Nurr1 expression. Lithium is also effective in several PD animal models. Lithium may be effective in dosages low enough to be available as an over-the counter (OTC) dietary supplement, which would greatly improve its worldwide accessibility compared to prescription medications. Both clinical trial and epidemiologic data suggest that lithium exposures of even <1mg a day may provide significant disease-modifying effects in neurodegenerative diseases including PD. We propose to assess the effects of 3 lithium dosages (2 OTC dosages and a “low-dose” prescription dosage) for 24 weeks on the above targets measured in blood in a randomized, parallel design, proof of concept clinical trial among 18 PD patients. Changes in plasma alpha-synuclein, PBMC Akt and GSK-3B levels as well as Nurr1 expression will be primary outcome measures. Results will identify the lithium dosage and PD subgroup(s) most appropriate to study in future PD trials.

2019-07-08

Coin holders:

Intracranial aneurysms (IAs) are potentially life-threatening vascular malformations, and the mainstay of modern treatment uses minimally invasive endovascular methods to occlude the lesion without the need for open surgery. Despite improvements in devices and approaches, up to 30% remain incompletely occluded, and thus at risk for rupture, at twelve months. The neurosurgery community currently lacks the ability to accurately identify which patients are at risk for poor outcomes at the time of presentation and treatment. Furthermore, after aneurysmal rupture, the largest source of morbidity and mortality is delayed cerebral ischemia due to vasospasm of the cerebrovasculature. Good clinical outcomes therefore require effective occlusion to prevent re-rupture, and early identification and aggressive management of vasospasm to prevent stroke. We plan to investigate the relationship between angiographic imaging biomarkers associated with contrast flow in Intracranial Aneurysms (IA) and treatment outcomes in order to develop a tool that improves our ability to predict success. The approach used to study these relations is to combine machine learning (ML) algorithms with Angiographic Parametric Imaging (API), also referred as colored Digital Subtraction Angiography. API imaging biomarkers and parametric maps will serve as input data and the treatment outcome will be used for output classification. Next we will study the correlation between API and vasospasm for ruptured IAs. Because API allows for both locally specific as well as global views of flow conditions, it is anticipated that quantitative assessment combined with trained ML algorithms will more accurately predict onset of vasospasm than qualitative human assessment. Early recognition and appropriate management of IAs addresses the objective of the UB to accelerate the field of stroke research and will help clinicians who manage these patients, including stroke neurologists, and neurosurgeons.

2019-06-13

Coin holders:

New Faculty:

Bradley

Lake Erie is vital source of drinking water. During periods of rainfall and snowmelt, untreated or partially treated wastewater is discharged into the Lake through sewer overflows (SOs). These sewer overflows represent a serious human health risk. But, quantifying the human health risk is challenging in large part due to knowledge gaps around the microbial and genetic composition of sewage pollution, how the sewage microbial community interacts with the environmental microbial community, and the persistence of sewage-associated pathogens and genes in the environment. The MinION portable DNA sequencer by Oxford Nanopore Technologies is the first DNA sequencer that can be used in the field to sequence all the DNA in a sample in real time. Previously, a sample would be collected and analyzed for a small portion of one gene associated with one microorganism in the lab days after the sample is collected. Now, data from the MinION can be used to examine the microbial community composition, the functionality of that community, the presence of viruses (which cannot be identified through amplicon sequencing) and the presence of antimicrobial resistance genes (which could lead to the spread of antimicrobial resistance) all in one sample analyzed as soon as the sample is collected and the DNA extracted. Drs. Sassoubre and Bradley have experience looking at single genetic markers of sewage-associated microorganisms but never in real time and never in conjunction with pathogens and antimicrobial resistance genes which directly impact human health. Dr. Zola’s expertise is necessary to be able to efficiently turn the voltage signal from the MinION into a DNA sequence with a taxonomic assignment all in just minutes to hours using a portable laptop. The proposed research will significantly change our understanding of the human health risks and environmental processes associated with sewage pollution in drinking water sources and has relevance both domestically and internationally.

2019-06-13

Coin holders:

Lithium-ion polymer batteries (LiPo) contain solid-phase polymer electrolytes as a conductive medium for charge migration. In addition to eliminating flammable organic solvents comprising traditional Li-ion batteries, LiPo cells can be manufactured in a variety of form factors and have the highest energy-per-mass across all battery types. Existing polymers used in LiPo cells typically contain electronegative heteroatoms or functional groups for interactions with cationic Li+, for example poly(ethylene oxide) (PEO). The goal of this Buffalo Blue Sky Collaboration is to address the shortfalls of existing PEO polymers for energy storage by designing novel polymer electrolytes with design principles of increasing ether-oxygen content and discovering new functional groups to interact with Li+. We hypothesize that these molecular-level changes will result in high lithium ion conductivities and ultimately enable LiPo cells that operate at room temperature. The Buffalo Blue Sky team draws upon our skills of polymer synthesis (Rzayev), thin film and membrane design (Lin), and electrochemical analysis (Cook), for the complete fabrication and characterization of next-generation polymer electrolytes and is an entirely unique research direction that aligns with the strengths of each research group.

2019-06-04

Coin holders:

New Faculty:

jiyeonk

Degeneration of central dopamine (DA) neurons is the key pathological feature of the brain aging diseases (Alzheimer's and Parkinson's Disease - PD/AD) and its symptoms including motor and cognitive deficits. Currently, there are no neuroprotective treatments for the diseases, however, understanding differential vulnerability among heterogeneous DA neurons may lead to neuromodulation treatments. Here, the hypothalamic A11 DA neurons are hypothesized to have a role in modulating movement via encoding sensory stimulus intensities, serving as a “sensory” DA system. However, the exact link between the A11 DA system and sensory stimuli/movement remains unclear due to limitations of in vivo methods to selectively determine and manipulate rapid DA signaling. Our central hypothesis is that (1) dysfunction of the A11 DA system is a critical contributor to motor/cognitive deficits and (2) manipulation of altered DA systems with patterned sensory stimulation/movement in a virtual reality (VR) setting may ameliorate the deficits. Our objective of this proposal is to develop the experimental setup and collect preliminary data to support our hypothesis. Aim 1. Establish a VR-based movement analysis setup for clinical and preclinical studies to understand the effects of sensory stimulation/movement on physical and cognitive functions. Aim 2. Determine how the A11 DA system encodes sensory stimuli and motor outputs using rat models of PD/AD via integration of novel DA sensing, VR-based movement analysis and neuromodulation. Our expertise in various fields (Dr. Park - DA sensing and manipulation with animal models; Dr. Tomita – Aging related cognitive deficits, Dr. Andrzejewski - a Movement Disorders Neurologist; Drs. Kang and Dutta - VR based neuromodulation and motion analysis) will allow a bench-to-bedside approach, transitioning from preclinical to clinical applications.

2019-05-23

Coin holders:

The development of polymeric nanomedicine for cancer is often hindered by the limited approaches available for evaluating its performance in human physiological conditions. We propose an integrated experimental platform that consists of a lab-on-chip in vitro model and an animal cancer model for polymeric nanomedicine performance evaluation. We will develop new poly(ethylene glycol) (PEG)-zwitterionic (ZW) hybrid copolymers as the model self-assembled nanomaterials and test their performance in the integrated evaluation system. Both PEG and ZW polymers are commonly used biomaterials with biomedical-relevant merits; however, their broad biomedical applications have been significantly restricted by the concerns of immunogenicity and bioactivity hindrance of PEG and the low processability of ZW polymers, respectively. Here, we hypothesize that integration of PEG with ZW polymer will create novel hybrid copolymers with synergistic effects to combine biomedical-relevant merits of both PEG and ZW polymers and to minimize unfavorable properties of each component. We will synthesize and characterize a series of PEG-ZW hybrid copolymers. We will then develop PEG-ZW hybrid copolymer-based nanodrug formulations to deliver doxorubincin, a chemotherapeutic drug, for breast cancer. We will develop a microfluidic channel-coupled human microtumor array system to examine the circulation time, targeting efficiency and therapeutic efficacy of these nanodrug formulations under fluidic shear. Such results will be compared to the therapeutic efficacy obtained from xenograft breast cancer models. It is expected that the successful development of an integrated, physiologically-relevant evaluation system will open up new opportunities for the future development of polymeric nanomedicines for various diseases. This project will benefit from the complementary expertise of our team in polymer science (Cheng), engineered microtissue system (Zhao), nanomedicine and cancer animal models (Wu).

2019-04-22

Coin holders:

New Faculty:

kameliam

Traditional methods for building protection against earthquakes are largely based on seismic isolators and energy dampers integrated in the lateral load resisting frame of the structure. While an effective “damage control” solution, the conventional approach fails to intercept and attenuate incident seismic waves before they reach the structure. Furthermore, materials with strong dissipative properties naturally exhibit below-average stiffness; bringing up inevitable trade-offs in strength and load-bearing capabilities. This project seeks to investigate the use of a class of artificially architected or engineered materials, or metamaterials, to address both of these challenges. The metamaterials will be inserted in foundation soil with the goal of constructing a vibrational shield around a given building or structural development. The internal structure and topology of metamaterials can be tailored at the macroscopic level to elicit an unconventional mechanical response to external loading and excitations. Such features culminate in damping-free vibroacoustic mitigation properties which cannot otherwise be achieved using natural and commonly available isotropic structures. Specifically, we will exploit the unique wave filtering and dispersion behavior of elastic metamaterials to mitigate seismic waves at band gap frequencies of interest. The project will further seek to simultaneously adapt and tune the metamaterial design to the accompanying geotechnical factors, including soil characteristics and in situ conditions, earthquake source, and nature of the destructive seismic waves. As such, the collaborative trio (cT) comprises complementary expertise in vibrations and acoustics, structural and earthquake engineering, as well as geomechanics.

2019-04-19

Coin holders:

In HIV patients, oral candidiasis/oral “thrush” is a common occurrence. Invasive candidiasis infections remain a serious cause of illness and morbidity in HIV positive (HIV+) drug users (DU+). The proposed study is focused on the evaluation of the oral microbiome in HIV+ patients with and without “thrush” and to additionally examine the effect of opiate abuse on periodontal diseases. Opiates can exacerbate periodontal diseases that constitute caries, gingiva inflammation, xerostomia, enamel erosion, and periodontitis. The microorganisms Porphyromonas gingivalis, Tannerella forsythia, and Treponema species (termed the “red-complex”) associated with periodontitis can also increase the risk of systemic diseases. The study involves recruitment of HIV+ patients with and without thrush and who abuse opiates from our immunodeficiency clinics at Evergreen Health Buffalo, NY. Periodontal disease assessment will be done in these patients at the UB dental school. We propose to evaluate the biodiversity of the oral microbiome in age and sex matched subjects: HIV+ drug users (HIV+ DU+) and HIV- drug users (HIV- DU+) with and without thrush, using high-throughput 16S rDNA sequencing to fully characterize the bacterial species and identify the fungal species present in oral mucosa/ saliva/ gingival plaque samples from these patient groups, and evaluate their association with levels of pro-inflammatory cytokines. This novel study is strengthened by the advanced computational and statistical analysis known as “translational bioinformatics” that will be used to analyze the high throughput data that will emerge from these microbiome studies. Defining the profiles of individual microbiomes will have immense impact on our understanding of effects of HIV and opiate use on oral and systemic health. Preliminary data generated will be used to apply to PA-18-699 Basic and Translational Oral Health Research Related to HIV/AIDS (R01).

2019-03-27

Coin holders:

Reward Deficiency Syndrome is a crucial factor in the etiology of substance, and non-substance addictive behaviors, like gambling and gaming. Increasing knowledge is needed about the genetic, neuroendocrine and psychological markers that predict bariatric surgery patients’ negative outcomes, such as addiction (ETOH, smoking, opioids, gambling), regain of weight, and diabetes and hypertension relapse. Early identification of these antecedents should be considered to develop a more personalized approach. The predictors of recidivism are not well understood. The Goal of this study is to identify biomarkers that predict which subjects undergoing bariatric surgery are at greater risk for recidivism of obesity, diabetes, hyperlipidemia, smoking or development of addictive disorders. Smoking and alcohol have also a negative surgical impact leading to development of ulcers at the anastomosis site. We will determine the specific genetic, endocrine, lifestyle, diet, and psychosocial factors that predict recidivism by examining over a 12-month period genetic, neuroendocrine and psychological biomarkers in 50 subjects prior to bariatric surgery. Drs. Quattrin, Thanos and Mastrandrea are complemented by junior and senior co-investigators with clinical (Harmon, Butch, Posner, Hoffman, Lamoshi, Leonard) and Bioinformatics expertise (Elkin). This multidisciplinary team will examine: a) Genetic markers (GARS genetic test examining single nucleotide polymorphisms detection of Reward Deficiency Syndrome); b) Neuroendocrine markers (glucose, insulin, ghrelin, GLP1) and c) Psychological markers (Questionnaire assessment of self-esteem, eating disorders, substance use, mental health, chronic stress, social support, physical activity). These data will be collected and analyzed along with patient outcomes and will be used to support a NIH proposal leading to a personalized approach of treatment for bariatric surgery (PAR-14-262 Long-Term Outcomes of Bariatric Surgery Using Large Data)

2019-03-20

Coin holders:

Soil moisture (SM) measurements are critical for efficient irrigation scheduling to determine when and how much water to apply to prevent over- or under-irrigation. Over-irrigation leads to fertilizer, energy, and water wastages with dire environmental consequences. Under-irrigation reduces plant quality and yield. SM is a vital factor that captures the state of the interplay between food-energy-water, making the monitoring and understanding of SM central to gaining insights into how the natural environment functions and responds to change. While spatial distributions of SM is dependent on multiple factors, conventional techniques for monitoring SM provide only point measurements that are spatially limited and unable to capture the joint behavior of the soil moisture regime. This proposal endeavors to develop a wireless sensor network to obtain saptio-temporal varying SM profiles will permits easy implementation of distributed control of irrigation in center-pivot irrigation. Specifically, we proposed a MI (Magnetic Induction) based large range SM sensing technique. While the MI wireless transceivers provide sufficient coverage range of the SM sensing, the collaborations among the distributed sensors in the field provide accurate estimation of SM even in the inhomogeneous underground environment. In this project, we will first develop the theoretical model to analyze and design the proposed system. Based on the model, we will implement the system in lab environment and initiate the experiments. Finally, field experiments using the developed testbed will be conducted to validate the proposed technique.

2019-03-05

Coin holders:

Obesity is a major risk factor for many chronic conditions and is associated with tremendous burden on the society. Current guidelines recommend metabolic and bariatric surgery (MBS) for patients with BMI≥40 or between 35 and 40 with obesity-related comorbidities and resistant to clinical interventions. African American (AA) patients are twice as likely to be diagnosed with diabetes and more than 3 times as likely to suffer from kidney failure as White patients. Although AA men have a high prevalence of obesity, they are the least likely group to receive MBS, trailing behind all other groups including AA women. This study will use semi-structured patient interviews and mobile surveys to address the following Specific Aim: (1) Explore whether and how intrinsic (acceptance, preference for, and beliefs about MBS) and extrinsic barriers (referral rate, employment, health insurance, and others) impact access to MBS (referral for consultation and odds of undergoing surgery) among AA men.

2019-03-01

Coin holders:

New Faculty:

kkong4

Smoking cessation during pregnancy can have substantial health benefits for both the mother and the offspring 1. One potential negative consequence is that smoking cessation often leads to overeating and excessive weight gain 2 perhaps due to increases in energy intake and changes in macronutrient preferences 3 that are not well understood, but could potentially be driven by changes in taste sensitivity after cessation. To date, no one has assessed motivation to eat, or the reinforcing value (RRV) of food, before and after smoking cessation to determine if increased RRV mediates increased energy intake and weight gain. Furthermore, no studies have been conducted in pregnant women who quit smoking to assess how shifts in RRV of food impact maternal weight gain. Finally, no one has closely examined changes in taste sensitivity and its relationship to RRV of food across pregnancy or after smoking cessation. We have shown that greater RRV of food is associated with excess weight gain 4 and that people who experience an increase in RRV of food over time gain significantly more weight than those who have stable or decreased RRV of food 4. A recent study suggests that greater RRV of food during pregnancy is associated with excess maternal weight gain 5. Much more work needs to be done to explore the relationship between RRV of food during pregnancy and excessive maternal weight gain and well as whether other factors, such as smoking cessation and infant feeding, that could mediate or moderate these relationships. The purpose of the proposed study is to examine the relationship among changes in RRV of food across pregnancy, maternal weight gain, and infant growth in women who are have quit smoking compared with women who continue to smoke and a non-smoking reference group. We will also examine potential moderators of this relationship, including socioeconomic status, pre-pregnancy BMI, and infant feeding modality.

2019-02-26

Coin holders:

Recent studies have revealed that genomic structural variants (SVs) are common in human populations and that they are major determinants of disease susceptibility. However, the evolutionary forces that shape structural variation remain incompletely understood. Gokcumen laboratory has a long-term goal to elucidate the evolutionary, biomedical and functional impact of human genomic structural variation. The objective for this proposal is to determine why a key example of a functional structural variation, the common deletion of the third exon of the growth hormone receptor (GHR) gene remains in human populations. The central hypothesis, based on preliminary analysis, is that GHRd3 has been adaptively maintained in human populations because even though it affects susceptibility to metabolic and developmental disorders, it also gives a fitness advantage in times of low food supply. The proposed work will integrate evolutionary genetics, cell biology, and mouse genetics to complete its objective and test the above-mentioned central hypothesis under three specific aims: (i) Elucidate the evolutionary history of GHRd3 and its links to human phenotype; (ii) Determine if GHRd3 affect transcriptome variation in multiple tissues; (iii) Determine the organismal-level effect of GHRd3 in a mouse model. We have now established a strong team of researchers at UB to tackle these questions. The results of our proposal will shed light on the functional mechanism and phenotypic impact of GHRd3, resulting in a better understanding of the genetic basis of a variety of developmental and metabolic disorders and providing the ability to fine-tune growth hormone treatments for patients carrying the deletion. On a broader scale, this study will provide a model for studying the evolutionary and functional impact of hundreds of complex structural variations that have been maintained in the human genome.

2019-02-08

Coin holders:

New Faculty:

junhchoi

The goal of this project is to develop multi-drone dispatch-and-routing optimization algorithms and exploit the potentials of microwave sensors for multi-drone enhanced post-disaster search operations. Microwave sensors have been used for through-the-wall imaging and remote sensing of vital signatures (e.g. heartbeats and respiratory movements). When such unique sensing capabilities are integrated on commercial drones, an efficient and low-cost search-and-rescue solution can be realized that can be particularly useful in situations where the target area is not accessible by ground units/vehicles. However, current microwave sensors mounted on drones operate suboptimally due to small drone sizes that limit the aperture dimension of the antenna. To further harness the technological potential of drone-mounted microwave sensors, we propose to explore “scout-and-summon” multi-drone routing schemes. The proposed method may be especially useful for post-disaster search operations that demand quick and accurate identification of survivors and the window for response is limited. In this scheme, the drones initially spread-out and scan for potential signatures of the survivors, and then group if needed to boost the confidence level of the detected signal prior to informing the rescue center to dispatch limited rescue resources to the correct locations in the most time efficient manner. Grouping of multiple drones enhances the spatial resolution of the microwave sensors to help pinpoint the exact location of the survivors and increases the strength of the reflected signals from the targets. To accomplish the proposed multi-drone routing scheme, this project will develop a 3D path planning optimization model and a suite of path updating models when new information is obtained from the sensor system. The outcomes of this project will serve as preliminary work for an NSF CPS proposal submission in May 2019. Funds from UB Blue Sky will be used to partially support two graduate students this semester, to generate initial model formulations and sensor results to be included in the proposal.

2019-02-08

Coin holders:

New Faculty:

baishakh

Rapid expansion of internet-of-things (IoT) will produce an extremely large volume of data from connected devices. While this raw data holds critical information and insights, it is extremely difficult for humans to parse large volume of data and take actions in real time. This is where artificial intelligence (AI) steps in to provide real-time actionable insights. While the synergistic relation between IoT and AI holds the key for success of IoT, there are several challenges with the current framework in which IoT device collects raw data and uses cloud services for storage and AI analysis before the decisions/insights are made available to the end-user. The 3 outstanding challenges are: i) transmission of large volume of data creates a bottleneck for communication network and increases latency; ii) use of cloud services increases probability for security breaches; and iii) use of rigid silicon electronics for IoT devices limits their use in the growing flexible devices market, which encompasses healthcare to consumer applications. To address the above-mentioned challenges, we will explore development of a new generation of “super-IoT” devices that will not require cloud services for AI based analysis and will also be flexible. The proposed IoT devices can lead to a new framework for IoT that will be more secure and also need less transmission bandwidth than the existing IoT devices. We envision that these new generation of IoT devices will find applications in a wide variety of fields, from healthcare to automotive to structural health monitoring.

2019-01-23

Coin holders:

New Faculty:

anirband

Ultrasound is emerging as a powerful, noninvasive method to affect human brain function. However, the effects of ultrasound on neuronal and vascular tissue in the brain are poorly understood. This limits the ability to harness the noninvasive ultrasound in basic neuroscience or human therapies. We propose to explore the mechanisms through both thermal and mechanical effects. Our proposal is based on the demonstration by Dr. Pralle that neurons in the brain can be modulated thermally using magnetic nanoparticles, and on the work of Dr. Bae on mechanical activation of the piezo1/2 channels and phosphoinositide signaling. Dr. Xia will contribute his expertise and resources in ultrasound instrumentation and physics. Dr. Dutta completes the team with his expertise in cerebrovascular medicine and neural engineering. In Aim 1, we propose to explore thermal effects of high-frequency ultrasound (4-8 MHz) to activate TRPV1 and TREK1 ion-channels in cell cultures and to develop ultrasound tools to cause a local temperature increase in the brain through the skull. In Aim 2, we propose to explore the mechanical effects of pulsed lower frequency ultrasound (100s kHz) to activate piezo1/2 channels and phosphoinositide signaling. For both aims, we will develop ultrasound tools and computational models to deliver the required energy into the brain through the skull. By the end of this pilot project, we will have preliminary data to support the mechanistic understanding of ultrasound stimulation. This preliminary data will be the backbone for federal research grant applications. This proposal is different from currently/past funded projects from each PI (Bae: vascular cell/tissue mechanobiology; Dutta: neuroimaging-guided head modeling; Pralle: magnetothermal neuronal research; and Xia: photoacoustic neural imaging) and the team has never collaborated to solve this puzzle through a joint effort.

2018-12-21

Coin holders:

Childhood obesity continues to be a public health concern. One predictor of weight status is the relative reinforcing value (RRV) of food, or how rewarding one finds eating versus alternative activities. Promoting rewarding activities that could take the place of eating offers a novel approach to decreasing excess energy intake and obesity. No studies have examined effects of promoting alternatives to eating on the RRV of food among preschoolers. Filling this gap is important, as this period involves drastic transitions, including increased autonomy and food preference learning. Prevention scientists have leveraged the opportunity for change during early childhood by testing parenting interventions, affecting outcomes such as socioemotional adjustment. We aim to bring together the food reinforcement and parenting intervention literature by promoting positive, rewarding parent-child interactions as a novel alternative to decrease the RRV of food. Children may find different activities rewarding, so we aim to develop a toolkit of activities within which positive parenting can be embedded (e.g., reading, nature walk). Then we will randomize parents and their 5 year olds to the intervention or control group. The intervention group will practice positive parenting, with flexibility in selecting activities in which parent-child interactions are embedded. Controls will be given items similar to those provided to the intervention group (e.g., books) but no parenting intervention. We will monitor activity selection and test intervention effects on the RRV of food versus parent-child interaction in the context of each family’s preferred activity. We will also explore secondary outcomes: e.g., child self-regulation. This study will inform a future grant by allowing development and feasibility testing of the intervention and tests of initial efficacy. This work has the potential to promote healthier eating, weight, and socioemotional development in early childhood and beyond.

2018-12-18

Coin holders:

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by functional destruction of the salivary and lacrimal glands, resulting in the loss of saliva and tear production. Currently, there is no cure for SS and treatment options are limited due to a lack of our overall understanding of the disease. Therefore, there is a critical need to identify key pathways and mediators that are important in the pathogenesis of this disease in the hope to facilitate earlier diagnosis of SS and to mitigate or abrogate the progression of this debilitating disease. Emerging evidence suggests a functional role for the epithelial cells in contributing to disease development and progression, in addition to abnormal immune cell responses. We hypothesize that there exists distinct sub-populations of cell types whose identification and characterization holds the key to the molecular secrets of SS. To investigate this, we will utilize a well-established mouse model that recapitulates human SS and perform single cell RNA-sequencing (scRNA-seq) of affected salivary glands. Furthermore, we will cross-reference our scRNA-seq based findings with transcriptomic datasets from human SS patients, to identify a conserved gene signature that defines the disease progression states. Long term, this will not only identify new biomarkers and therapeutic targets of SS but broadly also offer mechanistic insights for other autoimmune diseases with similar etiology and pathogenic underpinnings.

2018-12-17

Coin holders:

New Faculty:

rgunawan

Environmental mechanical cues play an important role in tissue development and regeneration, and these cues are distorted in aged stem cell populations. How aged stem cells transduce mechanical cues to modulate gene expression is the focus of this proposal. Our collaborative quatro consists of groups interested in how stem cell differentiation capacity and self-renewal potential are affected from a mechanical perspective as forces are converted to transcriptional activity. The Suchyna/Sachs group has expertise in biomechanical measurements, and have developed optical force sensors and genetically modified myoblast cell lines to dynamically monitor nuclear stress. The Andreadis group has expertise in tissue engineering, stem cell differentiation and reprogramming. Dr. Gunawan (new CBE faculty) lab has expertise in systems biology, bioinformatics and machine learning methods to interrogate and analyze large data sets. We have shown (Andreadis lab) that senescent myoblasts lose their ability to form functional myotubes, and that this regenerative capacity was restored completely by the transcription factor NANOG. In Aim 1 we propose to study how nuclear mechanical changes occurring in sarcopenia affect myogenesis and satellite cell population self-renewal. In Aim 2 we will determine how stress on the nuclear lamina of aged cells (in response to mechanical stimuli or substrate stiffness) is affected by NANOG. In Aim 3, we will combine high-throughput single-cell transcriptional profiling technology and the state-of-the-art bioinformatics analysis to determine transcriptionally-distinct cell (sub-)populations and to ascertain their gene expression and metabolic signatures. We will apply CALISTA (Clustering and Lineage Inference in Single-Cell Transcriptional Analysis), an in-house bioinformatics toolbox for single-cell transcriptomics analysis developed by the Gunawan group.

2018-12-17

Coin holders:

We found a novel method for the conversion of human pluripotent stem cells (hPSCs) from primed state to naïve state. These naïve hPSCs have all known properties of mouse embryonic stem cells that can be ethically tested. In this collaborative project, we will understand the mechanism of this epigenetic conversion by examining changes in transcriptome and DNA methylation. Dr. Feng will generate isogenic pairs of naïve and primed hPSCs. Dr. Buck and Dr. Liu will use RNAseq, ATACseq, CHIPseq to examine coordinated changes in the genome and correlate them to changes in DNA methylation. The goal is to build a bioinformatics pipeline to systematically understand epigenetic constraints of naïve pluripotency in human. Key targets identified in the project will be tested in the epigenetic conversion. The collaboration will lead to multi-PI R01 applications on this important topic.

2018-12-13

Coin holders:

The remarkable success of current cancer therapy, including radiation, chemotherapy, and transplantation, has enabled significant improvement in mortality and morbidity. There has been a clear shift from cancer survival alone to include quality of life with these treatments. Among the post-treatment complications, a major referral to dental clinics focus on oral mucositis, xerostomia, and dysgeusia (taste dysfunction). Various chemotherapy drugs have been shown to result in loss or aberrancies in a taste sensation that causes significant patient morbidity. While this loss is usually transient and usually recovers (often partially after treatment is stopped), the discomfort and perceptual imbalance leading to profound changes in diet and nutrition that has a major impact on their quality of life. Interestingly, the clinical observation of recovery of functional taste perception indicates there is an inherent ability for normal taste bud cell regeneration that could be potentially harnessed. Among various approaches in promoting oral wound healing, the use of low dose biophotonics treatments, termed Photobiomodulation (PBM) therapy, has shown remarkable efficacy. There is strong clinical evidence for the use of this therapy for oral mucositis and it is poised to become standard of care for all cancer patients receiving chemo, radiation or transplants to prevent oral mucositis. In this proposal, the Medler lab will generate a chemotherapy rat model, the Arany lab will develop PBM treatment protocols, the Medler-Torregrossa lab will analyze taste perception while the Scannapieco lab will analyze salivary changes affected by PBM therapy and taste recovery. These studies will generate critical preliminary data and tangibly demonstrate our collaborative efforts for a future full grant submission.

2018-12-07

Coin holders:

Green Infrastructure (GI) is a network of semi-natural constructions that use vegetation and engineered tools to manage stormwater in a cost-efficient way while providing several benefits to the communities in the surrounding areas. One of the many advantages of GI is the reduction of potential flooding events that may occur by controlling the water runoff of stormwater. The installation of GI is currently an endeavor mainly carried by local governments in public areas and, despite its potential benefits, it is uncommon to see such type of infrastructure in private land. Typical hurdles like the installation and maintenance costs as well as the lack of interest, knowledge, and means have prevented landowners to install GI in their property. Alas, having GI installed in private land has been proven to be highly beneficial for cities, specially in largely congested areas with no available public land suitable for GI. Several cities, like New York, Cincinnati, and Portland, have launched social programs that distribute monetary incentives to persuade local residents to voluntarily install GI in their land. However, identifying efficient policies that optimally distribute such incentives to maximize the effects of the new GI installations is still a major challenge. Among the many difficulties of designing such type of programs are the limited budget and the fact that the program must incorporate both the government social objective as well as each landowner's individual response within the incentive distribution process. That is, an efficient incentive program must be designed to anticipate the landowners response to strategically allocate the available resources and maximize the common good. We propose to tackle the problem of designing such incentive programs by using a two-stage framework that couples machine learning techniques and optimization models. The preliminary results obtained from this project will serve the development of a subsequent grant proposal.

2018-12-07

Coin holders:

New Faculty:

Q. Liu

Cannabis/marijuana is the most commonly-used regulated drug across developed countries. Recent changes in its legal status have led to: 1) more positive attitudes that it is less harmful; 2) greater access to cannabis, especially in states and countries that provide legal access to recreational cannabis; and, 3) increases in the prevalence of cannabis use. These effects may be particularly influential in the behavior of young adults (aged 18 to 30 years), who tend to show the highest prevalence of cannabis use and are most at risk for experiencing cannabis-related problems. The challenge for those who seek to monitor the potentially harmful effects of using cannabis is the lack of a noninvasive, but accurate, method for measuring the acute levels of tetrahydrocannabinol (THC, the active chemical of cannabis/marijuana). Our team has developed a highly sensitive nanophotonic chip to detect drugs (e.g. cocaine), that has received extensive interests from the public media (e.g. BBC and Mirror) and industry partners because, in part, the real world applications will be portable and require minimal technical expertise to use. In this seed project, we propose to develop an application of surface enhanced Raman spectroscopy to provide a reliable quantitative measure for sensing cannabis use. Specifically, we will develop and optimize the nanophotonic chip to enhance the Raman signals of chemical molecules bound to its surface and develop a particular surface treatment to capture THC and related chemicals. Strategies to realize quantitative sensing will require the highly uniform response of these nanostructures. Biological samples will be collected and tested on the proposed nano-chip. Finally, we will test its performance using portable Raman spectroscopy by working with our industry partners to explore the commercial potential of this tool in its broader field applications which include research, law enforcement, health care, and occupational fitness.

2018-11-15

Coin holders:

New Faculty:

jacktsen

Systematic lupus erythematosus (SLE) is a complex autoimmune disease, with prevalence in the adult U.S. population estimated at 24-150 cases per 100K patients. At least 5 out of 10 SLE adults develop lupus nephritis (LN), and depending on the disease classification, up to 30% of patients progress to renal failure within 15 years. Existing methods to score histological activity and chronicity from LN renal biopsies correlate poorly with the progression of LN, and inadequately predict LN outcome from initial biopsies. Neutrophils and their extracellular defense mechanisms such as NETs (neutrophilic extracellular traps) have been implicated in autoimmune diseases. NET’s detected in glomeruli of human LN renal biopsies have been correlated with proteinuria and may play a role in LN progression. Rigorous computational and biological tools to quantify and understand NET functionality in whole slide images (WSIs) of LN biopsies have yet to be established. Such tools would clarify the role of NETs, as potential digital early-indicators of LN outcome, and may shed light on the chronic pathogenesis of LN. Our interdisciplinary team, with expertise in neutrophil biology and imaging (Dr. Michelle Visser), computational renal pathology (Dr. Pinaki Sarder), and 3D anatomical modeling (new UB faculty Dr. Jack Tseng), is interested in understanding the role of NETs in LN. We will 1) use immunofluorescence and landmark-based 3D geometric approaches to accurately study NETs in LN tissue biopsies and 2) develop computational methods to detect, segment, and quantify NETs detected in LN renal biopsies from fluorescence microscopy images of thin renal tissue sections. This proposal will allow us to generate data for future grant proposals examining NET functionality during LN, as well as potential novel diagnostic tools.

2018-11-15

Coin holders:

We present a concept of selective metal removal from aqueous streams based upon the solution phase and solid phase binding of natural products called siderophores. In this project, a novel siderophore product, methanobactin, will be studied computationally and, later, experimentally through the combined expertise of the collaborative trio. Chosen for the potential to bind numerous metal compounds (including precious and toxic species), methanobactin will be computationally modeled using density functional theory by Drs. Dupuis and Pfeifer in both a solution and immobilized environment based upon structural variations that could affect metal removal capacity in each state. Simultaneously, the concept of solution phase versus immobilized phase metal binding differences will be tested experimentally by Drs. Pfeifer and Atkinson based upon combined expertise in siderophore production and surface characterization of traditional immobilization matrices (such as activated carbon and polymeric resins) and continually informed throughout the project by the predictive outcomes of the aforementioned computational modeling work. The project is new by virtue of novel partnerships or approaches (or both) regarding natural product biosynthesis (Pfeifer), computational modeling (Dupuis), and solid phase characterization (Atkinson). Also highlighting novelty will be a new siderophore product, methanobactin, which has not previously been studied by this group of scientists. Finally, the research potential is broad and unique, offering future dual directions in environmental and economic conservation.

2018-10-26

Coin holders:

Weather, including atmospheric conditions and pavement conditions, can adversely influence vehicle and driver behavior and cause issues in transportation safety and mobility. Conditions such as wet and icy pavement, snow storms, and high wind, may impact both vehicle sensors and how drivers react and switch from self-driving mode to manual. Along with the development of automated vehicles, there is a pressing need to understand how vehicles and drivers will detect and react to adverse weather at different levels of automation. This study will investigate how inclement weather and pavement conditions affect driving behavior, vehicle dynamics, vehicle operations, and sensor performance (e.g. cameras and Lidar) at different levels of automation. Several experiments will be conducted for data collection on UB campuses. The project will provide inputs and suggestions on developing USDOT policy on automated vehicles operations under inclement weather. Also, this project will allow us to submit follow-up proposals aiming to increase the reliability and safety of controlling automated vehicles under different conditions.

2018-10-26

Coin holders:

Design has been regarded as a service- and design-driven process for hundreds of years. With the recent development of computer design systems and smart-building techniques, there is a need to study a new performance-based and value-driven design process. Several decision makers and stakeholders are involved in the design cycle, including designers, developers, finance sector, regulators, contractors, manufacturers, and end users. Although those decision makers may have different (and often conflicting) perspectives, values, and resources, they may jointly and subconsciously determine the effectiveness and success of the design process through discussion, negotiation, and contracts. However, designers do not consciously integrate decision analysis and game theory into their design processes. This proposal fills this gap by using normative models (e.g., expected utility theory) to generate robust design strategies, within a game-theoretic framework where descriptive models (e.g., prospect theory) are used to model the stakeholders' behaviors. Multi-attribute utility theory will be used to model the tradeoffs between stakeholders' values for aesthetics, functionality, economics, comfort, sustainability, and safety during the design process. Game theory will be used to study strategic interactions among multiple stakeholders to identify win-win cooperation solutions. The research objectives of this project are to generate a new high-level modeling framework for a multi-agency process for architecture and engineering design. This project will address under-studied questions such as: How to systematically integrate stakeholder preferences into the design process to build a robust partnership while considering that designers or developers may have conflicting preferences and/or behave irrationally? The models will be validated and improved using case studies, simulation, and experiments.

2018-09-28

Coin holders:

The characterization of radicals generated via Fenton-like reactions in sustainable chemical applications is a challenging endeavor that requires specialized spectroscopies and chemical techniques. However, the properties and effects of these radicals remain elusive owing to their low concentrations, which is inherently linked to their high-reactivities. Electron paramagnetic resonance (EPR) spectroscopy is a specialized technique that is highly sensitive to radicals. The Lacy research group has unique expertise in the use of EPR instrumentation and the Dai lab has expertise in the reactivity and fate of Fenton-species. A problem that we aim to address is the removal of deleterious Fenton side reactions of iron catalysts interfaced with organic ionomers and proton exchange membranes in fuel cells, which cause significant performance degradation. Fundamental understanding on the relevant reaction mechanism would greatly benefit the catalyst design that the Wu group is pursuing. Hence, we are seeking to identify the radical products and their fates as it relates to improving the iron catalyst longevity and stability. The Dai lab has expertise in the fates of these radicals and we intend to incorporate sacrificial molecules to quench the Fenton radicals. Additional synergistic components include the purposeful generation of Fenton reagents by electrochemical means. Therefore, the knowledge gained from studying the Fenton reagents in Gang Wu’s fuel cells will benefit other new projects in the Lacy and Dai lab. The crux of this collaboration is the triune expertise in Fenton reactions and the essential use of EPR spectroscopy. The latter component provides an innovative approach that is not used in application-based sciences such as fuel cells or environmental science. The proposed science is currently not funded by any of the three PI’s.

2018-09-27

Coin holders:

New Faculty:

hongyues

3D printing has become the main driving force of the third industrial revolution by fundamentally transforming the product design and manufacturing. Owing to the wide accessibility and high usability, 3D printers are increasingly exploited by malicious users to fabricate illegal (e.g., keys and gun parts), unlawful (e.g., counterfeiting a patented product), and artificially defective (e.g., embedding hidden cracks in UAV wings) products. To date, 3D printing has raised a host of unprecedented legal challenges since it could be utilized for fabricating potential unaccountable criminal tools for strengthening the public safety and security. Concerned about the misuse of 3D printing technology, the U.S. Department of State urged International Traffic in Arms Regulation (ITAR) to limit the proliferation of 3D printed criminal tools. However, these regulations have a varying degree of efficacy and are inadequate, by themselves, to deal with the rapid growth of 3D printers. To this end, our team plans to take the first exploratory research activity and investigate how to use technologies to establish ethical 3D printing in three folds: (1) Legality: 3D printing cannot produce illegal/unlawful products and parts; (2) Assurance: 3D printing cannot fabricate the products/parts with hidden cracks (which might sabotage the objects of interest), intentionally or unintentionally; (3) Accountability: if someone abuses 3D printing, we are able to identify the source 3D printers, which immensely aids the forensic investigation. The team will investigate in the ontology of illegal and unsafe factors, and design novel algorithms for their pre-screening, detection and prevention of unethical behaviors of 3D printing. This project is highly interdisciplinary with the convergence of manufacturing, informatics and artificial intelligence.

2018-09-20

Coin holders:

Fragile X syndrome (FX) is the leading inherited cause of autism spectrum disorder (ASD). Most individuals with ASD suffer from auditory hypersensitivity disorders, an extreme negative reaction to everday sounds. We will use an Frm1 KO rat model of FX to develop a mechanistic understanding of auditory hypersensitivity disorders in FX and ASD that can be used to treat ASD. Aim 1 will use novel behavioral assays to characterize auditory hypersensitivity disorders in this model and high-resolution in vivo electrophysiology to quantify neural hyperactivity in auditory cortex. Aim 2 will use employ whole-cell voltage-clamp recordings from auditory cortex brain slices to identify disturbances in excitatory/inhibitory synaptic currents and action potential firing related to hyperexcitability. Aim 3 will employ gel-free LC/MS to obtain high-resolution, large-scale protein expression profiles to discover disease biomarkers and rational drug treatments for neural hyperactivity.

2018-09-18

Coin holders:

Data from occupational and general public settings overwhelmingly indicate that conditions promoting physiological stress (e.g., fatigue, heat, cold, dehydration) increase the risk of physical injury and accidents. It is believed that this elevated risk is due to changes in mental and/or physical function. However, experimental testing has rarely captured the neurobehavioral changes proposed to potentiate the risk of physical injury and accidents under physiological stress. We hypothesize that this is because the available experimental tools are inappropriate for examining acute changes in neurobehavioral function. With this background, our project aims to refine neurobehavioral measurements for repeated measures study designs. The goal is to identify approaches that are sensitive to acute neurobehavioral changes occurring secondary to physiological stress. This will allow us to submit grant proposals aiming to explore the underlying mechanisms and potential countermeasures.

Presented by University at Buffalo - Research and Economic Development
Buffalo Blue Sky © 2019