2019 RESEARCH SEED AWARDS
“Education, Not Deportation": Immigrant Law and Medical Students' Experiences Across Legal Status
As scholars and policy makers alike have noted, currently there is urgent need for increased numbers of culturally competent professionals in the legal and medical fields. This is particularly important given the decisive role medical and legal services play in the everyday lives of community members. Also, given recent developments in federal immigration policies, increased numbers of undocumented students have been able to enroll in professional degree programs. Social science research has largely examined undocumented students’ experiences along the educational pipeline separate from that of their U.S. citizen, legal permanent resident peers. This project seeks to bridge this gap by examining the experiences of immigrant students -- documented and undocumented -- alongside one another to focus on the role legal status plays in shaping educational access and post-graduate opportunities. Employing the use of a mixed methods approach consisting of an online survey of immigrant law and medical degree students and in-depth interviews, this project aims to create a database that can be of use to future scholars interested in issues of immigration, educational equity, and the legal and healthcare professions.
PI: Kevin Escudero, Assistant Professor of American Studies
Co-PIs: Tina M. Park, Ph.D. candidate in Sociology; Rachel Freeman, Ph.D. candidate in Education, UCLA; Vania Pereira, M.A. candidate in American Studies; Marco Antonio Flores, M.A. candidate in Art History, Williams College
A Collaborative Research Initiative on Children’s Alternative Care
UNICEF estimates that there are approximately 153 million orphaned and abandoned children worldwide, most in low- and middle-income countries. While roughly 2.7 million children reside in formal institutional care such as orphanages (Petrowski et al 2017), millions more live in “alternative care,” which includes care with extended kin, foster care, and family-like care. Efforts to support children in need of alternative care are complicated by a lack of rigorous academic research that can be used to inform best practices and program design. Our project on children’s alternative care will bring together Brown faculty in anthropology, sociology, public health who have expertise in studying children’s alternative care and child and family health and well-being. Our goal is to develop a large-scale, multi-disciplinary project on alternative care in low- and middle-income countries. In partnership with global and local care providers, we propose to study how different experiences of alternative care affect child health and resilience, shape conceptions of identity for children and their caregivers, and explore how public health, policy, community and family contexts are related to caregiver and child experiences and well-being. In so doing, we seek to produce results that expand scientific understanding of alternative care, and inform efforts to advocate for and provide care for children in need around the world.
Political Knowledge and Citizenship in Developing Country Democracies
James Madison famously wrote that a “popular government, without popular information or the means of acquiring it, is but a prologue to a farce or a tragedy.” In recent years, citizen political knowledge and the challenges of misinformation have received substantial attention in the United States and other wealthy democracies. Of note, however, is the fact that a majority of citizens living under democratic governments today live in lower and middle-income countries. In these contexts, citizen knowledge is crucial not only for making voting decisions, but for gaining access to basic rights and entitlements. There is surprisingly little research on citizen political knowledge in lower and middle income democracies, how that knowledge affects voting and other political behaviors, and the conditions under which citizens invest greater time and effort in acquiring relevant political knowledge. This is part of a larger project in which we will carry out large citizen surveys in a number of lower and middle-income democracies, including Brazil and Indonesia (the latter funded by Brown's Seed grant). These surveys will explore how best to measure political knowledge, the links between knowledge and the ability to exercise the full rights of citizenship, as well as the conditions that lead citizens to acquire political knowledge from reputable sources. Another outcome of this project will be the development of a new battery of political knowledge questions that can be used in single-country and cross-national surveys in democracies across the developing world.
PI: Rebecca Weitz-Shapiro, Associate Professor of Political Science
Co-PI: Matthew Winters, Associate Professor of Political Science, University of Illinois at Urbana-Champaign
Biological and Life Sciences
The neural architecture of political polarization: How polarized perception arises and how to overcome it
Humanity’s greatest triumphs require extensive cooperation between people with opposing viewpoints, but this principle is under threat from political polarization. At the heart of polarization lies ‘polarized perception’: our political beliefs fundamentally change the way we perceive the world. This can, in turn, intensify our beliefs and undermine cooperation. To design effective interventions against polarization, it is crucial to understand which psychological mechanisms drive polarized perception. Despite the urgency of this problem, it remains largely unknown which psychological mechanisms contribute to polarization, impeding finding successful interventions. The aims of this proposal are to establish a new theoretical and methodological model for studying polarization, and to use cutting-edge methods in neuroscience, including inter-subject neural synchrony, to identify which components of this model give rise to political polarization. Crucially, this approach will identify which elements of political communication (e.g. emotional language) elicit the greatest polarized perception, which can yield promising new avenues for tackling the increasing polarization we see unfolding in society. This project will thus initiate a highly innovative research line aimed at understanding polarization from a neuropsychological perspective, while also providing practical solutions. By building bridges between traditionally distant fields and bringing in knowledge on state-of-the-art methodology, this research will advance the position of Brown University in psychology, political science, and neuroscience. An OVPR Research Seed Fund award will allow us to demonstrate how neuroscience can revolutionize polarization research, forge collaborations with leading experts around the world, and secure the external funding needed to discover how we overcome political polarization.
PI: Oriel FeldmanHall, Assistant Professor of Cognitive, Linguistic & Psychological Sciences
Co-PI: Jeroen Van Baar, Postdoctoral Research Associate in Cognitive, Linguistic & Psychological Sciences
Progressive neurodegeneration in mouse models of amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive degradation of neuromuscular connectivity, leading to widespread paralysis and ultimately death of affected individuals. Effective therapeutic intervention in ALS presents an unmet medical need, and accurate animal models of the disease are required as a proving ground for treatment approaches. We have recently begun to characterize a novel genetic knock-in model of ALS in mice, and our preliminary findings provide strong evidence for muscle denervation and motor deficits in this mouse line. We hypothesize that these mice are an accurate disease model that recapitulates the progressive neurodegenerative features, focal spread, and sex-specific differences of ALS. We propose to further characterize neuromuscular deficits in this mouse line, using both anatomical and behavioral criteria to follow symptomatic progression in different muscle groups of both male and female mice over time. Insights gained from these initial studies will position us to compare multiple ALS models, discover common disease mechanisms, and provide a reference framework for assessing the effectiveness of various manipulations that might delay or prevent symptomatic progression. Thus, our work is an important step towards the development of therapeutic strategies for ALS.
PI: Alexander Jaworski, June G. Zimmerman Assistant Professor of Brain Science, Assistant Professor of Neuroscience
Key Personnel: Diane Lipscombe, Thomas J. Watson, Sr. Professor of Science, Professor of Neuroscience; Justin Fallon, Professor of Medical Science, Professor of Psychiatry and Human Behavior; Eric Morrow, Mencoff Family Associate Professor of Biology, Associate Professor of Neuroscience, Associate Professor of Psychiatry and Human Behavior
Drug discovery for falciparum malaria
The overall aim of this application is to discover novel therapeutics for Plasmodium falciparum malaria. P. falciparum is a leading cause of morbidity and mortality in developing countries, infecting hundreds of millions of individuals and killing over one million children each year. The spread of parasites resistant to the artemisinin family of compounds threatens recent progress achieved by antimalarial campaigns and underscores the urgent need to identify new anti-malarial drugs. In previous work, we discovered PfGARP, a previously unrecognized parasite protein found on the exofacial surface of parasite-infected erythrocytes. Antibodies to PfGARP inhibit parasite growth in vitro by 99% compared to controls in the absence of any immune effector molecules (complement) or cells- thus the remarkable anti-parasite effect of anti-PfGARP results from antibody binding alone. The Scientific Premise of this application is that PfGARP is a high value, druggable target based on: 1) its surface expression on infected RBCs, 2) the absence of any significant amino acid homology with human host proteins, and 3) the ability of antibody binding to PfGARP to kill essentially all exposed parasites within 12 hours.In this application, we will screen a large drug library (30 million compounds) to identify drugs that bind to PfGARP and mimic the activity of anti-PfGARP antibodies, resulting in rapid parasite death.
PI: Jonathan Kurtis Stanley M. Aronson Professor of Pathology and Laboratory Medicine, Chair of Pathology and Laboratory Medicine, Professor of Pathology and Laboratory Medicine
Redox-Mediated Control of Protein Structure as a Potential Therapy for Inflammation
Macrophage migration inhibitory factor (MIF) is critical to the pathophysiology of inflammation and MIF inhibition or its deficiency in MIF-/- mice is strongly correlated with a reduction in respiratory disease symptoms. MIF promotes pro-inflammatory signaling through interactions with proteins involved in cellular redox regulation and its structure is believed to be sensitive to changes in cellular redox conditions. The potential to leverage this sensitivity to design effective MIF inhibitors will be enhanced by a detailed understanding of its redox-dependent properties, which have not been characterized. Such inhibitors have promising therapeutic value for treatment of inflammatory diseases, but these efforts are stalled by the lack of structural and dynamical information about the redox-dependent interactions of MIF with partner proteins, receptors and small molecules. Our preliminary data show that the MIF structure and conformational motions are altered by solution redox properties. I hypothesize that MIF modifies its structure in response to local redox potentials and that this conformational flexibility allows MIF to toggle its interactions with pro-inflammatory proteins, modulating downstream biological responses. This hypothesis will be tested by investigating the redox-dependent structure and conformational dynamics of MIF as well as its structure in complex with its CD74 receptor and redox proteins thioredoxin and ribosomal protein S19. The redox-dependence of drug-like ligand interaction with MIF will be determined to advance a novel approach toward selective MIF inhibition that will add to a strong track record of quality investigations into inflammatory/respiratory pathologies at Brown and may ultimately aid in the treatment of inflammatory diseases.
PI: George Lisi, Assistant Professor of Molecular Biology, Cell Biology & Biochemistry
Collaborator: Elias Lolis, Professor of Pharmacology, Yale School of Medicine
Structural Basis of Viral Attack on Innate Immunity
Promyelocytic Leukemia Nuclear Bodies (PML-NBs) are dynamic sub-nuclear organelles formed by protein PML and Sp100, with important contributions from the Small Ubiquitin-like MOdifier (SUMO) and numerous different partner proteins. Traditionally these have been studied in association with the acute promyelocytic leukemia, and are known to indirectly regulate diverse cellular processes like transcription, apoptosis, DNA replication, and epigenetic silencing. PML-NBs are also known to regulate the innate immune signaling pathways and have emerged as integral components of the host antiviral response. Recent studies show viruses have evolved mechanisms to disarm PML-NBs suggesting new functional roles played by them. Despite the high functional significance, we lack an understanding of interactions between PML-NB constituents and viral proteins. We show that JC and BK human polyomavirus interact differently with PML-NBs. This proposal is an attempt to bridge enigmatic knowledge gap by applying powerful NMR spectroscopy to elucidate the structural basis for PML-NB disruption by BKPyV.
The function of the extraocular Opsin 3 receptor in the brain
Visual phototransduction has received much attention over the past decades, while nonvisual phototransduction has been slower to gain interest despite sustaining equally important functions: from entraining circadian rhythms, to facilitating photorelaxation of blood vessels. The first mammalian extraocular opsins was identified twenty years ago in the hypothalamus and aptly named encephalopsin or opsin 3 (OPN3). Although we have recently discovered a function for OPN3 in the regulation of skin pigmentation, its function in the brain remains unknown. The goal of the proposed experiments is to understand the signaling mechanisms of OPN3 in the mammalian hypothalamus. Based on our preliminary data, the central hypothesis of this proposal is that OPN3 physically and functionally regulates melanocortin 3 receptor (MC3R) in the hypothalamus to negatively mediate energy balance. We will first investigate the cellular co-localization of OPN3 and MC3R in the hypothalamus using a novel OPN3-mCherry mouse that we recently generated, then test the functional interaction of the two receptors by measuring the receptor-mediated changes in cellular cAMP. These studies will uncover a novel functional role of mammalian OPN3 in the brain and will broaden our understanding of nonvisual phototransduction
PI: Elena Oancea, Associate Professor of Medical Science
Neural mechanisms of object recognition by hand and eye
The connection between eye and hand, or vision and touch, has puzzled philosophers, psychologists, and neuroscientists for hundreds of years. In the past few decades, considerable progress has been made in understanding mechanisms of visual recognition. Indeed, for primates, perceptual experience is very much dominated by vision and a large proportion of the brain is dedicated to visual processing. At the same time, however, knowing how we recognize objects by vision should not be mistaken for understanding how we know what objects are. This project will explore how we recognize objects by vision and by touch, and attempt to uncover the neural circuits by which this information is shared through the concerted activity of neurons in the brain. Understanding how the brain merges multiple sources of information into stable and meaningful representations of objects is of significant interest in that it can provide clues as to how these same circuits may result in dissociations between the senses in psychiatric disease.
PI: David Sheinberg, Professor of Neuroscience
Collaborator: Ryan Miller, Postdoctoral Fellow in Neuroscience
Structure and mechanics of the bat shoulder: Testing a new model for human rotator cuff disorders
To date, mice have served as the primary animal model for disorders of the human shoulder. However, mice differ from humans in fundamental and critical ways that limit this approach: during locomotion, impact loads apply compression/bending to the forelimb; mice experience relatively few loading cycles over their short lives; and mouse shoulder anatomy and patterns of motion differ greatly from those of humans. In contrast, bats are long-lived (typically 15 to 35 years), and their natural flight patterns entail a very large number of locomotor cycles (over 1,200,000 over 15 years). Anatomy of the bat shoulder skeleton, muscles, and tendons resembles that of humans remarkably closely, and shoulder motions used by bats during flight appear to closely match those of humans during high stress, injury-causing activities (throwing, swimming, racquet power strokes, overhead hammering). Moreover, the structures of the human-like bat rotator cuff appear to withstand mechanical demands that are extreme, in magnitude and number of repetitions, without the wear or damage that frequently result from occupational and athletic activities in humans. To determine feasibility of use of our laboratory bat colonies as a model for ongoing study, and specifically to develop collaborative proposals to NSF and NIH (with G. Genin, Washington University and S. Thomopolous, Columbia University), we propose to carry out two foundational analyses. We aim to demonstrate achievability of 1) accurate capture of 3D shoulder kinematics during controlled flight (wind tunnel and obstacle course) and swimming with XROMM, and 2) direct measurement of shoulder muscle activity patterns.
PI: Sharon Swartz, Professor of Biology, Professor of Engineering
BMP4 signaling in brain development and epilepsy
Epilepsy, often a consequence of abnormal neurological development, is a major co-morbidity of intellectual disability. Disruptions in brain development result in abnormal circuits that underlie functional neuronal deficits and alterations in homeostasis causing seizures. BMP4 is expressed in areas of the developing ventral forebrain that give rise to interneuron populations implicated in epilepsy. Studying the role of critical developmental signals, such as BMP4, that also appear to be important in epilepsy, has been hindered by the lack of good models, since the complete loss of gene function results in lethality early in development. We have generated mouse models that are partial loss of function for BMP4 signaling. These BMP4 mutant mice display severe epilepsy as adults with evidence of a change in the size of the cortex at 2 months. At that age, we observe the onset of epileptiform discharges. By late adulthood, we see an increase in cortical thickness in the mutant brains vs control. We propose that loss of fine-tuned BMP signaling causes neuronal and glial defects leading to epilepsy. We will test this hypothesis: Aim 1: Determine effect of dysregulated BMP4 signaling on cortical activity. Using video EEG, we will test our hypothesis that dysregulation of BMP signaling leads to progressive abnormal circuit dysfunction and epilepsy. Aim 2: Determine effect of compromised BMP4 signaling on brain structures implicated in epilepsy. We will test our hypothesis that abnormal BMP4 signaling causes structural changes underlying epilepsy, including changes in neural architecture and possible alterations in glial structure and function.
PI: Kristi Wharton, Professor of Biology
Co-PI: Judy Liu, Sidney A. Fox and Dorothea Doctors Fox Professor of Ophthalmology and Visual Science, Assistant Professor of Neurology, and Assistant Professor of Molecular Biology, Cell Biology & Biochemistry
Key Personnel: Allyson Sherman-Roe, Research Assistant in Molecular Biology, Cell Biology & Biochemistry
A novel gene therapy targeting cardiac fibroblast electrical remodeling to reduce fatal arrhythmias after heart attack
When an athlete suddenly drops to the ground and dies during competition, the cause is often “sudden cardiac death,” a medical term that means there was a severe problem with the electrical activity of the heart that caused it to stop beating. As we age, we all have an increased likelihood of developing heart disease, like having a heart attack or developing atrial fibrillation. Many of these heart conditions have interrupted electrical activity, called arrhythmias, yet current medical care for arrhythmia is technically challenging and often carries great risks, including worsening the problem. We aim to develop new, targeted gene therapies for arrhythmia by specifically instructing the fibroblasts of the heart to help manage the electrical patterns. These cells are very active and change their behavior as we age and particularly after a heart attack, becoming more agitated and excitable. Our research aims to calm down the electrical activity of fibroblasts and reduce fatal arrhythmias. To do this, we formed a multi-disciplinary team of experts in cardiac arrhythmia mechanisms, tissue engineering, and gene therapy. This project is expected to launch a new research enterprise at Brown that will lead the field in developing an understanding of fibroblast-driven arrhythmia mechanisms and advancing novel therapeutic strategies to treat arrhythmia and lessen the risks for sudden cardiac death.
PI: Kareen Coulombe, Assistant Professor of Engineering, Assistant Professor of Molecular Pharmacology, Physiology and Biotechnology
Co-PI: Bum-Rak Choi, Associate Professor of Medicine (Research)
Collaborators: Peng Zhang, Assistant Professor of Medicine; Ulrike Mende, Professor of Medicine
Key Personnel: Collin Polucha, Research Technician, Engineering; Tae Yun Kim, Postdoctoral Fellow, Medicine; Peter Bronk, Research Scientist, Medicine; Karim Roder, Assistant Professor of Medicine (Research)
Probing the role of mechanical forces in tissue assembly using in situ force sensors
The forces cells exert, and have exerted on them in return, play a critical role in early development, wound healing, and disease. However, these forces are not easily investigated, nor have they been quantified within 3D, cell-dense tissues. This information is critical for understanding cellular interactions necessary for tissue assembly and repair. The proposed project will investigate the role of intercellular forces in cell-dense structures. To accomplish this, we will quantify cell traction forces in 3D constructs by embedding discrete, hyper-compliant microparticles (HCMPs) alongside living cells and monitoring the resultant deformations. Existing approaches for quantifying traction forces require measuring the displacement of fiducial markers in bulk, deformable materials. That approach is not compatible for studying cell-only neotissues that serve as models of native tissue building. Instead, we will embed a small number of HCMPs of defined size (25 µm) and elastic modulus (100 Pa) alongside thousands of cells as they self-assemble into geometrically defined microtissues (spheroid and toroid shapes). Serial images of deformed HCMPs will be captured using a high-content confocal microscope and then computationally assessed to determine applied cellular forces. We will investigate differences for mesenchymal and epithelial cell types, as well as for integrin- vs. cadherin-coated HCMPs. Mechanistic understanding will be pursued using cytoskeleton-targeting drug treatments. This project will produce critical knowledge about how mechanics influences neotissue self-assembly and organization. By better understanding how cells exert forces on one another, we can begin to grasp how to direct these behaviors towards regenerative applications.
PI: Eric Darling, Associate Professor of Medical Science, Associate Professor of Engineering, Associate Professor of Orthopaedics
Co-PI: Haneesh Kesari, Assistant Professor of Engineering
Co-PI: Jeffrey Morgan, Professor of Medical Science, Professor of Engineering
Forecasting Patterns of Delirium and Early Recovery After Acute Stroke*
Delirium is common after acute stroke, and likely represents an impediment to recovery. However, the concrete manifestations of delirium comprise a spectrum, and it is unclear whether various patterns of symptoms may have differential effects on outcomes. Many of these symptoms are intimately connected, including arousal, attention, and activity level, and as a result, delirium phenotypes have been traditionally labeled as hyperactive, hypoactive, and mixed. Unfortunately, patients with hypoactive delirium are known to be underdiagnosed using standard screening tools, and the presence of pre-existing neurological symptoms only magnifies this challenge. We therefore propose an innovative approach aimed at diagnosing and categorizing delirium using wearable sensors capable of measuring activity on a granular scale. Activity data will then be analyzed using machine learning techniques to identify delirium phenotypes corresponding to patient activity patterns. We hypothesize that such patterns may also be predictive of early motor recovery after stroke, and we propose to apply similar machine learning techniques to identify activity-based phenotypes corresponding to post-stroke functional outcomes. We aim to leverage Rhode Island Hospital’s strength in clinical stroke care and Brown University’s expertise in biomedical informatics to build a collaborative partnership that will allow both institutions to become leaders in the field of translational stroke research. It is anticipated that the co-PIs of the proposed study will continue their collaboration to build a competitive research program based on novel data acquisition and analysis techniques. The insights obtained from this study will be used as crucial preliminary work enabling future NIH R01 funding applications.
PI: Michael Reznik, Assistant Professor of Neurology, Assistant Professor of Neurosurgery
Co-PI: Carsten Eickhoff, Assistant Professor of Medical Science, Assistant Professor of Computer Science
Enhancing Wound Healing Using Hydrogels for Localized Chemokine Delivery
Wound healing is an essential process in human health, and poorly healing wounds can lead to secondary infections, permanent disablement, and increased mortality. The Jamieson lab studies the role of the innate immune response in wound healing. We found that poorly healing wounds have a decrease in innate immune cells infiltrate. The immune suppression included lower levels of chemokines, which are essential to attract cells of the immune system. The wound healing rate could be restored by exogenous addition of the chemokines CXCL1 and CCL2. However, the materials used to apply chemokines had to be applied daily, which is not practical in a clinical setting. Therefore, we propose to develop chemokine delivering biomaterials that can be used to enhance wound healing. In the proposed work, we will build on expertise from PI Shukla’s lab on the development of hydrogel drug delivery materials and the expertise of PI Jamieson’s lab in the innate immune response and in vivo wound models, to develop and examine the efficacy of new chemokine releasing hydrogel materials. The mechanical properties of these hydrogels will be investigated along with the in vitro release and chemokine activity. Hydrogel formulations will be tested in vivo in two animal models of wound healing. Successful completion of this collaboration will pave the way for the development of a new research program using novel materials to improve wound healing. This research will be relevant to a variety of patient populations.
PI: Anita Shukla, Assistant Professor of Engineering, Assistant Professor of Molecular Pharmacology, Physiology and Biotechnology
Co-PI: Amanda Jamieson, Assistant Professor of Molecular Microbiology and Immunology
Building a Large Dataset of Articulated 3D Object Models
People spend a large percentage of their lives indoors: in bedrooms, living rooms, offices, kitchens, etc. The demand for virtual versions of these spaces has never been higher, with virtual reality, augmented reality, online furniture retail, computer vision, and robotics applications all requiring high-fidelity virtual environments. To be truly compelling, a virtual interior space must support the same interactions as its real-world counterpart: VR users expect to interact with the scene around them, and interaction with the surrounding environment is crucial for training autonomous robots (e.g. opening doors and cabinets). Most object interactions are characterized by the way the object's parts move or articulate. Unfortunately, it is difficult to create interactive scenes at the scale demanded by the applications above because there do not exist enough articulated 3D object models. Large static object databases exist, but the few existing articulated shape databases are several orders of magnitude smaller.To address this critical need, I propose to create a large dataset of articulated 3D object models: that is, each model in the dataset has a type and a range of motion annotated for each of its movable parts. This dataset will be of the same order of magnitude as the largest existing static shape databases. I will accomplish this goal by aggregating 3D models from existing static shape databases and then annotating them with part articulations. I will conduct the annotation process at scale using crowdsourcing tools (such as Amazon Mechanical Turk) by developing an easy-to-use, web-based annotation interface.
PI: Daniel Ritchie, Assistant Professor of Computer Science
Real-time View Synthesis for Robot Virtual Reality Teleoperation
Live virtual reality (VR) video is important for robotic teleoperation because the greater situational awareness and presence from VR help to increase robot control efficiency and effectiveness. However, in VR video, there is often a large difference between the freedom of movement afforded to the human operator by the VR tracking system and the freedom of view afforded by the camera system. This means that VR video often causes fatigue or sickness. To overcome this, light field cameras are required to help match the camera view to the VR motion parallax. We aim to develop a new real-time technique for view interpolation for VR robot teleoperation. A cheap and high-quality motion parallax solution will make VR video formats more able to meet the needs of complex robot remote control tasks.
Next Generation Brain Mapping of Meditative States: Toward Clinically-Viable Neurofeedback
There is a growing evidence base for the benefits of meditation on health, ranging from addiction to anxiety, depression, chronic pain and others. Much progress has been made in linking the quality of meditation to brain activity for the purpose of identifying neural mechanisms and developing neurofeedback for clinical use. This includes identification of key brain regions (e.g. the posterior cingulate cortex) associated with crucial aspects of the meditative experience (e.g. effortless awareness). This causal link between meditation and brain activity has been established by functional magnetic resonance imaging (fMRI), though the clinical utility of this modality is limited by prohibitive cost and low temporal resolution among others. We have been exploring source-estimated electroencephalography (EEG) as an alternative, though it has its own limitations, including proneness to artifact and low signal to noise ratios. Brown University is somewhat unique in having equipment that can bridge the gaps and capitalize on simultaneous strengths of fMRI and EEG by combining the two (simultaneous fMRI/EEG measurement). Our aims are to identify EEG correlates of PCC activity (as measured by simultaneous fMRI/EEG recording); and to develop a setup that can confirm that identified EEG correlates are specific to PCC activity and can be used for real-time neurofeedback. The methods and technology that will result from this project will benefit the Brown neuroscience research community, as it will lay the groundwork and foundation for simultaneous fMRI/EEG neurofeedback methods that can be used by cognitive neuroscientists across the university for studying a multitude of research questions.
Markers of Premature Biological Aging in Chronically Homeless Individuals*
Individuals that experience homelessness have higher age-adjusted mortality than domiciled counterparts. Multiple factors might contribute to these effects, but one understudied possibility is that exposure to homelessness may cause a phenomenon known as premature biological aging (PBA). PBA occurs when an individual’s biology suggests they are older than their years. Epidemiologic research, including our work, indicates that geriatric conditions in the chronically homeless are found at levels that suggest PBA of as much as 20 years, yet molecular studies have not been done. We must understand the effects of chronic homelessness on a molecular level to inform the development of targeted interventions (i.e., pinpointing the biological systems that contribute to increased mortality to identify new targets for treatment). We propose to fill key gaps in the literature and develop pilot data (i.e., big epigenetic data) to support an R01 grant application. Our primary study aims are to: 1): Examine associations of chronic and one-time short-term homelessness and premature biological aging (via DNA methylation and telomere length profiles), and 2) Identify which CpG sites are most differentially methylated by chronic and one-time homelessness. Our proposed work is highly innovative and would be the first in the country to examine PBA in individuals with prolonged exposure to an environmental stress (i.e., homelessness). We have assembled an interdisciplinary team of researchers from Brown and the Department of Veteran Affairs with a shared long-term goal of developing a research program centered on using state-of-the-art data analytics to improve health care for homeless individuals.
PI: Eric Jutkowitz, Assistant Professor of Health Services, Policy and Practice
Co-PI: John McGeary, Associate Professor of Psychiatry and Human Behavior
Co-Is: James Rudolph, Professor of Medicine, Professor of Health Services, Policy and Practice; Thomas O’Toole, Professor of Medicine; Hung-Teh Kao, Associate Professor of Psychiatry & Human Behavior (Research), Lorin Crawford, Assistant Professor of Biostatistics
Medications and the Risk of Motor Vehicle Crashes in Older Drivers
Motor vehicle crashes (MVCs) are a major source of morbidity and mortality for adults aged ≥65, resulting in 6,800 deaths and over 191,000 non-fatal injuries treated in emergency departments annually. Despite the common belief that prescription drug use is a leading cause of MVCs, after nearly three decades of research, data are scarce and controversy remains about the effects of medications on MVCs in older adults. A major barrier to progress has been the lack of detailed linked data on MVCs, prescription drug use, and age-related medical conditions. We propose to close this gap by linking detailed licensing and crash histories from over 2.3 million licensed drivers aged ≥65 to rich clinical and prescription drug data. Our aims are to 1) compile and link the New Jersey Traffic Safety Outcomes data to Medicare Parts A and D claims, and 2) describe the frequency and patterns of driving in older adults stratified by medication use and dose. Our proposal builds on Brown’s world-renowned reputation in aging and growing reputation in pharmacoepidemiology by expanding to a critical new area—transportation. Three products will result from the proposed initial effort: 1) a multi-institutional, multi-disciplinary research group with the Children’s Hospital of Philadelphia; 2) a unique data source that can be used to answer a wide array of medication-related and other research questions on transportation in older adults; and 3) conception of a research portfolio of topics centered on transportation and aging. Thus, we will be well-positioned to submit an R01 proposal responsive to National Institute on Aging Strategic Goals C and E.
PI: Andrew Zullo, Assistant Professor of Health Services, Policy and Practice, Assistant Professor of Epidemiology
Key Personnel: Nina Joyce, Assistant Professor of Health Services, Policy and Practice; Allison E. Curry, Assistant Professor of Pediatrics, Division of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, and Senior Scientist and Director of Epidemiology and Biostatistics, Center for Injury Research and Prevention, Children’s Hospital of Philadelphia; Melissa R. Pfeiffer, Senior Biostatistician, Center for Injury Research and Prevention, Children’s Hospital of Philadelphia
*Big Data Collaborative Seed Award co-funded with the Data Science Initiative