University Of Rochester

NSF Awards · FY 2024 · 2024-09

Plastics have been found in all aquatic realms, from groundwater to the most remote areas of the global ocean, but estimates of their abundance, depth variability, longevity, and impact on marine biogeochemical cycles are unknown. The goal of this project is to determine how the presence of microplastics in the ocean may impact the distribution of naturally-occurring radioactive isotopes. These isotopes are commonly used to track processes associated with natural particles like sediments and biological materials. Plastics have different chemical and physical properties than natural particles. These differences may affect how isotopes “stick” to particles, and change how oceanographers use the isotopes to calculate things like how fast particles sink through the ocean. The team will use a combination of laboratory experiments and field work to investigate these questions. The project will facilitate the training of graduate and undergraduate researchers from the University of Rochester and incorporate unique educational experiences for undergraduates and local high school students. One graduate student’s PhD work and two undergraduate senior theses will focus on aspects of this project. The investigators will also engage with high school students from Rochester City School District (RCSD) in two workshops focused on “the radioactivity around us” and how radioisotopes are used to answer big questions in earth sciences and beyond. The workshops will be offered through the Upward Bound program, which has a proven track record of increasing college admission rates for RCSD students. Persistent, buoyant, and metals-scavenging plastics have the potential to impact tracer distributions, especially for longer-lived isotopes, as a lateral source and/or as a standing stock at depths could obscure or contribute to natural variations. While the ultimate goal is to know what tracers stick to (i.e., to plastics or to associated biochemical materials), the most pressing question is to what degree do particle-reactive radioisotopes associate with microplastics (MPs) in the marine environment and does this behavior differ from the typical associations observed for the average ocean particle? Specifically, do MPs have comparable partition coefficients (Kds) to bulk particles for key radioisotope tracers, and how different are Kds with location or varying biogeochemical conditions? The project will address three objectives. Objective 1 is to quantify the association (Kds) of select particle-reactive radioisotopes with plastics in controlled environments through laboratory experiments. Objective 2 is to quantify the association (relative Kds) of select particle-reactive radioisotopes with plastics at a coastal and open ocean location to determine whether a gradient could exist. Finally, Objective 3 is to assess whether there is a potential for ‘inherited’ radioisotope signals to come from plastics with terrestrial origins or introductions, through collection of sediment cores from beaches and estuaries. If the proposed work shows that MPs have some potential for impacting radioisotope distributions (hypothesis 1: plastics Kds ≥ typical particle Kds) or that MPs have the greatest potential for impacting radioisotope distributions (hypothesis 2: plastics Kds ≥ typical particle Kds and observed gradients suggest inherited tracer signals could be transported in a manner unique to plastics), observational radiochemists and modelers will have a baseline to account for the ‘plastics effect’. Collectively, the field of chemical oceanography can begin to study the significance of plastics for various elemental cycles and incorporate the ‘plastics effect’ into future efforts focused on key marine tracers. Currently, this type of proposal, and marine plastics studies in general, sit on the edge of several existing programs. The proposed work can be used directly for future decision making on paired plastics-radioisotopes and general tracer studies by NSF Chemical Oceanography and other agencies. If, after the proposed work is carried out, there is little to no predicted impact of microplastics on radioisotope tracer distribution in the oceans (the ‘null’ hypothesis), the ongoing debate of the effect of plastics will be closed but radioisotopes will be established as tracers of plastics. In this case, the proposed measurements will produce upper ocean plastics fluxes and residence times. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-09

Abstract Hip osteoarthritis (OA) affects one in four people by the age of 85, and it is linked to abnormal hip morphology including Cam-type femoroacetabular impingement (FAI). Hence, symptomatic FAI represents an ideal condition to identify key regulators in hip OA progression. To this end, we performed RNA sequencing (RNA- seq) comparing FAI and hip OA cartilage, revealing that WNT16 expression is negatively correlated with OA severity. We also showed that WNT16 is decreased during cartilage cell (i.e., chondrocyte) hypertrophy (a hallmark of OA) and that WNT16 is up-regulated in chondrocytes under mechanical loading. As Transient Receptor Potential Vanilloid 4 (TRPV4), a Ca2+-permeable ion channel, is an essential mechanosensor in chondrocytes, our results suggest a novel link between TRPV4, WNT16, and chondrocyte mechanobiology. Our preliminary data predict that WNT16 in chondrocytes is potentially regulated by TRPV4-mediated signaling pathways, and WNT16 inhibits chondrocyte hypertrophy via G protein-associated signal transduction. Thus, to elucidate the functional role of WNT16 in hip OA pathogenesis and develop novel therapies, we propose the following aims: Specific Aim 1: To determine the genetic and epigenetic mechanism(s) of mechanoinduction of WNT16 in chondrocytes. Agarose constructs encapsulating human stem cell-derived chondrocytes and hip primary chondrocytes will be subjected to loading in combination of TRPV4 activator/inhibitor, and their effects on WNT16 will be assessed. We will use novel next-generation sequencing to identify genetic and epigenetic factors that regulate WNT16 expression in chondrocytes. Specific Aim 2: To determine the effects of WNT16 gain- and loss-of-function on chondrocyte specification, hypertrophy, and hip OA development. We will investigate if cartilage-specific Wnt16 knockout mice exhibit enhanced hip OA compared to control mice. We will measure OA severity, synovitis, and bone remodeling. We will also quantify behavioral changes and pain responses, as well as determine the association of these measurements with hip OA severity. We will use human hip primary chondrocytes with WNT16 modulation to investigate its effects on hypertrophy. Specific Aim 3: To elucidate altered chondrocyte cell-cell crosstalk in hip healthy/FAI/OA cartilage and to determine if WNT16 mRNA delivery can mitigate hip OA by restoring normal WNT signaling among chondrocyte crosstalk. We will fully characterize distinct chondrocyte phenotypes in human healthy, FAI, and OA hip cartilage by integrating scRNA/Spatial-seq datasets. We will determine if WNT16 mRNA delivery using nanoparticles to hip FAI/OA cartilage explants is sufficient to mitigate hip OA progression. Impact: A mechanistic understanding of the role of WNT16 in hip cartilage homeostasis and FAI/OA will provide insights into the development of therapeutic interventions for hip OA by targeting WNT16 signaling.

NIH Research Projects · FY 2025 · 2024-09

Lewy-body dementia (LBD) is a neurodegenerative illness and the most common of a spectrum of Parkinsonian disorders called Parkinson’s and related disorders (PDRD). Notably, Lewy-body dementia has been specifically named by NIH as an Alzheimer’s and Related disorder (ADRD) and an area of high priority research. LBD includes Dementia with Lewy bodies, an illness characterized by early dementia, hallucinations and parkinsonism, and Parkinson’s Disease Dementia, an occurrence that affects over 75% of people with Parkinson’s and the leading cause of carepartner distress in this population. Despite this, carepartner support for LBD is not routinely addressed in current models of care, even when compared to other ADRDs. When it is addressed, the focus is on carepartner burden reduction. Support is likely to be incomplete, and possibly even harmful, when provided solely through a burden lens especially as carepartners themselves believe that there are positive aspects of caregiving and that it can be fulfilling. Providing adequate carepartner support is challenging without knowledge of carepartners’ views on caregiving and what matters to them. Stakeholder engagement research methods offer an important way to address this knowledge gap. The long-term goal is to use stakeholder engagement research methods to partner with carepartners and multidisciplinary teams and develop, test, and promote interventions and programs that promote balanced and carepartner-driven approaches to carepartner support. This proposal’s research objectives are to identify the dimensions and positive and negative aspects of LBD caregiving, adapt and co-design a peer-led intervention for this population, and conduct a pilot clinical trial. An intervention developed with LBD carepartners that goes beyond burden can improve carepartner preparedness, and wellbeing, and decrease social isolation. This is based on evidence from peer-led interventions in other diseases that have channeled the experiences and motivation of former carepartners to successfully address current carepartner concerns. This proposal has three specific aims: (1) Identify dimensions of LBD caregiving by collaborating with key stakeholders, (2) Adapt & design a peer-led pilot intervention for and with LBD carepartners, and (3) Assess feasibility and acceptability of the pilot intervention. The approach is innovative as it is the first within the field of Neurology to (a) identify what matters most to carepartners, (b) use stakeholder engagement research methods from design to delivery of an intervention, and (c) utilize a user centered design framework. The training objectives of this proposal will build on the applicant’s prior research experiences to learn new skills related to (1) Stakeholder Engagement Methods, (2) Intervention Adaptation and co-design, and (3) Design of Clinical Trials.

NIH Research Projects · FY 2025 · 2024-09

Inhibitory control deficits are a core feature of schizophrenia spectrum disorders (SSDs), with clear manifestations seen in psychophysiological, electrophysiological, and neuroanatomical measures of these processes. Addressing these symptoms is of critical clinical relevance since they are a main predictor of negative vocational and psychosocial outcomes. An intriguing set of findings has suggested physical activity and exercise can have a positive effect on SSD symptomatology, but the exercise-linked neural changes that may result in improved inhibitory control is unknown. Mobile Brain/Body Imaging (MoBI) technologies enable the assessment of cognitive control processes in participants using high-density electroencephalography (hd-EEG) during task performance and physical activity. During the F99 phase, using cutting-edge MoBI technologies, I will test if a single acute walking intervention will mitigate behavioral and neurophysiological indices of inhibitory control deficits in SSDs (Aim 1A) and if individuals with SSDs showing significant improvement in inhibitory control performance and normalization of inhibition-related event-related-potential (ERP) components to neurotypical adults have less severe psychosis symptoms (Aim 1B). In Aim 2, I examine the underlying structural-functional neural bases and behavior of disturbances in cognitive control and sensory processing among people with and at risk for SSDs. Upon completion of both phases, I will become a multimodal neuroimaging and computational psychiatry expert in SSDs. Learning neuroimaging methods (fMRI) and computational models to stimulate the complex dynamics of brain function and behavior, alongside environmental factors, will enable me to identify the underlying mechanisms of SSDs and propel the field forward in developing personalized treatments. The training received during the F99/K00 phases will prepare me for the transition to a faculty position at a R1 institution, where I will lead a distinguished neuroscience program and implement educational opportunities with initiatives to expand access to neuroscience education and instill a passion for science to young individuals of the local community. As an expert in multimodal neuroimaging and computational psychiatry, I will continue pursuing similar K00 research, expanding my focus to include individuals with psychosis across all stages of illness, prodromal, early and chronic, to investigate variations in the sensory-cognitive neural circuits underlying auditory and visual hallucinations, as well as develop personalized treatment algorithms. I am firmly committed to providing practical, tractable solutions to individuals with SSDs through basic knowledge.

NIH Research Projects · FY 2025 · 2024-08

Following injury, tendon heals via a fibrotic scar-mediated process. This fibrotic response impairs restoration of tendon structure and function, and there are currently no pharmacological approaches in standard use to enhance the healing process. While the overall cell environment during healing is dynamic and complex, myofibroblasts are key regulators of the healing process. During tendon healing, tenocytes undergo progressive activation and differentiation in to myofibroblasts. Myofibroblasts synthesize, contract and remodel the new extracellular matrix that is required for restoring tissue integrity. However, resolution of physiological healing requires clearance of myofibroblasts, either via apoptosis or reversion to a basal fibroblast/tenocyte state. Tissue fibrosis, including fibrotic tendon healing results from myofibroblast persistence. Indeed, we have previously shown that tendon scar tissue from both mouse and humans is enriched for myofibroblasts that take on an anti-apoptotic profile. As such, understanding the mechanisms, and identifying therapeutic approaches to modulate myofibroblast dynamics during healing would fill critical knowledge gaps. We and others have recently demonstrated that expression of the proton-sensing G-protein coupled receptor Gpr68/Ogr1 is decreased during tissue fibrosis. Moreover, small molecule activation of Gpr68 can modulate both myofibroblast differentiation and reversion of lung fibroblasts. Thus, in this high-risk high-reward proposal we will define the efficacy of pharmacological activation of Gpr68 to modulate tenocyte-myofibroblast dynamics during fibrotic tendon healing. In addition, our preliminary data suggest that changes in macrophage-specific Gpr68 expression during healing underpin several aspects of myofibroblast function. The on-going interaction between macrophages and myofibroblast is an important regulator of both physiological and fibrotic wound healing. Therefore, we will dissect the cell-type specifics functions of Gpr68 in modulating tendon healing, and in responding to small molecule activation of Gpr68. Successful completion of these studies will provide important fundamental information related to regulation of the cell environment during tendon healing, and will establish a novel pharmacological approach to enhance the tendon healing process.

NSF Awards · FY 2024 · 2024-08

The National Science Foundation (NSF) Graduate Research Fellowship Program (GRFP) is a highly competitive, federal fellowship program. GRFP helps ensure the vitality and diversity of the scientific and engineering workforce of the United States. The program recognizes and supports outstanding graduate students who are pursuing research-based master's and doctoral degrees in science, technology, engineering, and mathematics (STEM) and in STEM education. The GRFP provides three years of financial support for the graduate education of individuals who have demonstrated their potential for significant research achievements in STEM and STEM education. This award supports the NSF Graduate Fellows pursuing graduate education at this GRFP institution. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

The analysis, simulation, & applications of the nonlinear fluid equations like the Euler equations or the Navier-Stokes equations, is an important (if not a vital) part of many areas of Science, Technology, Engineering, and Mathematics (STEM). The research in this project concerns a variety of projects on the rigorous derivations of these macroscopic continuum equations from basic microscopic quantum particle models and elucidates how the macroscopic fluid-defining quantities like pressure or viscosity emerge from the averaging of microscopic quantities. Examples of the boson particles we study includes the nitrogen and oxygen molecules (99.03% volume of air) and 99.95% of the water molecules. The number of particles in these many-body systems is on the order of magnitude of the Avogadro constant, which make the microscopic simulation of such systems impossible. The mathematical justification of these macroscopic continuum limits for the many-body systems they are supposed to describe, is therefore an issue of fundamental scientific importance. The principal investigator is committed to introducing undergraduate and graduate students to experiments and cutting-edge mathematics, advising PhD students and mentoring postdoctoral researchers. The particular scope of this research project is to investigate several problems concerning the fine properties of solutions to the time-dependent many-body Schrödinger equation when the particle number tends to infinity and the Planck constant tends to zero. This research project encompasses three broad directions. The first direction concerns the proof of the classical incompressible Euler equations as a direct limit of quantum many-body dynamics and find the microscopic quantity corresponding to the macroscopic Mach number. The second direction is to rigorously extract the hierarchy structure for the compressible Euler equations induced by quantum many-body dynamics and identify the microscopic quantity which becomes the macroscopic Knudsen number. The third direction turns to the study of the optimal well/ill-posedness separation and the fine nonlinear structure of solutions regarding the important mesoscopic Boltzmann equations via new dispersive methods. The PI and collaborators use techniques from harmonic analysis, probability, and spectral theory to analyze these problems. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-08

Brain and Behavioral Mechanisms Linking Loneliness and Social Isolation with Accelerated Cognitive Aging and Alzheimer’s Disease and Related Dementias Loneliness and social isolation (SIL) increase risk for all ten leading causes of death in the U.S. and are strongly linked to cognitive decline and Alzheimer’s Disease and Related Dementias (ADRD). Reducing SIL can foster healthy aging, improve mental and physical health, optimize quality of life, and prevent cognitive decline and ADRD. However, healthcare has not capitalized on promoting social connection as preventive medicine: it is not routinely assessed nor treated, in part because current data do not allow for definitive conclusions about evidence-based approaches. Dr. Van Orden’s research aims to identify evidence-based strategies for SIL—grounded in the study of mechanisms—to promote healthy aging and increase quality of life for older adults. In line with NIA priorities of increasing understanding of the aging brain and ADRD; developing interventions to address ADRD and promote healthy brain aging; and understanding mechanisms underlying effective interventions, the objective of this mid-career K24 award in patient-oriented research (POR) is to incorporate the study of cognition and healthy brain aging into Dr. Van Orden’s research on SIL interventions to understand benefits for brain aging (and preventing ADRD) as well as identifying intervention targets to optimize interventions. This K24 will allow her to develop capacity in interdisciplinary science in healthy brain aging by co-mentoring clinical scientists who study ADRD as well as basic scientists in neuroscience (and related disciplines) to foster development of a program of research on the translational science of SIL and its role in brain aging. Dr. Van Orden’s long-term objective in POR is to identify and disseminate evidence-based interventions for SIL in later life, including determining the mechanisms that account for improved health outcomes—mental health, cognitive health, and physical health outcomes. The research project component of this proposal is designed to advance the translational science of SIL and brain aging while producing an optimal training laboratory for mentees. The scientific premise is that SIL and brain aging have reciprocal associations that can result in a downward spiral towards unhealthy brain aging and ADRD, or with intervention, an upward spiral towards healthy brain aging and social connection. To produce efficient training for mentees, the project relies on published data (meta-analysis) and secondary analyses of completed trials (from the PI’s laboratory and NIA-funded Roybal ADRD caregiving research center). The first aim is to examine whether behavioral interventions for SIL improve cognitive functioning. The second aim it to examine baseline cognitive impairment as a prognostic indicator for improvement in SIL. The third aim is to examine potential mechanisms for non-compliance to SIL interventions. We will integrate findings with the published literature on social and affective processing in SIL and the published literature on experimental studies with animal models of SIL to develop a testable model of brain and behavioral mechanisms that simultaneously maintain SIL and accelerate cognitive aging and that could serve as intervention targets to optimize interventions.

NIH Research Projects · FY 2025 · 2024-08

The Neely National Clinician-Scientist Mentorship Network of the Triological Society was created to provide career mentorship to young otolaryngologists interested in clinician-scientist careers with mentorship from established, NIH-funded otolaryngologist-scientists. The goals of the program are to support the development of otolaryngologists to become successful NIH-funded investigators, to strengthen the research training pipeline, and to support research among otolaryngologist-scientists. The current proposal details the activities of the Mentorship Network that will help mentees reach their goals. These activities include three in-person and eight virtual meetings annually, one-on-one mentoring opportunities, maintenance of a listserv, and mock grant reviews. In addition, the Network offers online, “just-in-time” educational materials for clinical research. The Neely National Clinician-Scientist Mentorship Network targets two pools of otolaryngology mentees. Mentees in the first pool have some research training experience but have yet to submit their first PI NIH grants. These mentees may be otolaryngology residents, fellows, or new faculty members. The second pool of mentees are those who have NIH funding in the form of an introductory grant (typically a K08 or K23 grant) and are looking to convert that grant to an R01 or similar independent award. Mentorship in the network is provided by a large cadre of successfully funded otolaryngologist-scientists many of whom are members of the Triological Society. The Network includes mentors whose research spans the breadth of NIDCD mission areas, including research in hearing, balance, speech, olfaction, and health outcomes, as well as other research areas related to otolaryngology, such as cancer and immunology. The research techniques and foci employed by the mentors are varied and include basic discovery in animals, clinical research, health services, disparities, and population-based research. The mentors come from various backgrounds and institutions across the country, and a significant strength of the proposal is the depth and breadth of the mentorship group. The Network is led by two experienced clinician-scientists with help from an experienced executive committee. Mentees will be recruited through a website developed for the Network, through direct outreach to otolaryngology departments, and through personal outreach by members of the Network. Continuous evaluation of the program by mentors and mentees will be used to improve the program. Outcome measures include the number of mentees participating, the retention of mentees throughout the program, and the success of mentees in securing NIH grants. This network is unique in otolaryngology and innovative in that there is no other national mentorship network for otolaryngologist-scientists.

NIH Research Projects · FY 2025 · 2024-08

G Protein coupled Receptors (GPCRs) regulate every aspect of human physiology. However, the endogenous ligands activating ~100 GPCRs are still unknown, hence they are named orphan GPCRs. Considering their understudied biology and established physiological roles, orphan GPCRs represent unexploited pharmacological targets. The quest for endogenous and synthetic compounds modulating their activity is significant for both understanding their biology and developing novel therapeutics. Using an innovative cell- based assay, we recently established Gi/o/z coupling for several orphan GPCRs. Building on this discovery, we optimized a platform to screen candidate ligands based on the heterologous co-expression of orphan GPCRs and a multicomponent activity biosensor. The ultimate goal of this project is to identify pharmacological modulators, endogenous ligands, and binding partners for GPR156, a clinically relevant target for the treatment of hearing and balance disorders with unexplored roles in the central nervous system. Our preliminary data support the feasibility of the approach and also establish the presence of endogenous ligands in the brain. Thus, the identification of these endogenous ligands will constitute an additional goal of our proposal that we will pursue applying innovative proximity-mediated labeling technologies. Activity of identified ligands and function of interacting proteins identified by proteomics analysis will be validated in a physiologically relevant system. In fact, GPR156 controls hair cell orientation in auditory and balance organs, with GPR156 gene mutations leading to deafness and balance disorders in patients. Finally, combining proteomics analysis and mouse genetics, we will define components of GPR156 signaling complex and determine their role in establishing planar cell polarity in the mouse inner ear.

NIH Research Projects · FY 2025 · 2024-08

This proposed Mentored Patient-Oriented Research Career Development Award will support Dr. Lachant’s advancement as a physician-scientist equipped to conduct independent research which sensibly utilizes emerging wearable technology and rehabilitation strategies to improve the lives of patients with heart and lung disease. The research project itself will study the impact of an electronically-delivered rehabilitation program early after hospitalization for acute pulmonary embolism. The proposed research study will build on a foundation of didactic coursework and provide an opportunity for mentored development in clinical trial design and execution. A key training goal will be to develop and automate analysis of novel end points using wearable technology (heart rate and activity); he will also gain expertise in biostatistics, management and analysis of massive data sets, and the role of exercise in disease. Completion of this award will allow Dr. Lachant to become an independent researcher performing decentralized clinical trials incorporating wearable devices in pulmonary vascular disease towards the goal of delivering optimal home rehabilitation programs. Residual dyspnea (Post-PE Syndrome) is common (~50%) after acute PE and is associated with increased morbidity and healthcare utilization. Exercise after acute pulmonary embolism is generally recommended in the 2019 European Society of Cardiology guidelines without any details (appropriate location, degree of intensity, type of monitoring). Dr. Lachant’s hypothesis is that an early rehabilitation program incorporating heart rate monitoring will reduce post PE syndrome by addressing deconditioning and anxiety, two factors associated with Post-PE syndrome. To test this hypothesis, Dr. Lachant will enroll patients hospitalized with acute pulmonary embolism into an electronically-delivered rehabilitation program within seven days of discharge. We will evaluate whether a prescriptive exercise program which gradually intensifies over 8 weeks is better than regular electronic contact to decrease Post-PE syndrome. Since Post-PE syndrome does not have a diagnostic test, he will evaluate multiple parameters as surrogates for Post-PE syndrome, including an end point combining a change in activity with a reduction in PEmb quality of life questionnaires (Aim 1). The optimal activity tracker wear time and exercise compliance will also be evaluated (Aim 2). We will be intentionally inclusive in our recruitment and seek to determine whether sex, race/ethnicity, or socioeconomic factors associate with outcomes or participation. The study results will provide invaluable data for Dr. Lachant to design a multicenter, prospective study implementing a decentralized, home-based rehabilitation after hospitalized acute PE. His project mentors are experts in exercise and rehabilitation (Karen Mustian, Ph.D, MPH) and pulmonary vascular disease (R. James White, MD, Ph.D); experts in pulmonary embolism clinical trials (Jeffrey Kline, MD) and Biomedical Engineering (Jean Pierre Couderc Ph.D) will assist with key training goals. This accomplished mentor team will help support his launch as an independent investigator.

NSF Awards · FY 2024 · 2024-08

Song is present in every known human culture, fosters social bonding, and has substantial therapeutic value. To perceive song, the human brain must solve some of the most difficult challenges of hearing, including isolating singing from musical accompaniment and integrating speech, rhythmic, and melodic information. Recently, a neural population was discovered in the human brain that responds strongly to singing and weakly to both speech and instrumental music. The discovery of this neural population provides a unique opportunity to understand the brain mechanisms of song perception and how these mechanisms differ from those used to perceive other sounds including music and speech more generally. Leveraging this discovery, this project answers key questions about how song is coded in the human brain leveraging advanced experimental and computational methods. The project engages high school and undergraduate students from diverse backgrounds to participate in interdisciplinary research at the intersection of artificial intelligence, statistics, and neuroscience. The data and methods developed in this project are carefully documented and shared, ensuring they have a broad impact, and the project disseminates findings to a wide audience through, for example, science media and museums to help foster continued interest and support for scientific research. The project measures cortical responses to singing using functional MRI (fMRI) and intracranial recordings from human neurosurgical patients. Intracranial recordings provide a rare opportunity to measure human brain responses with very high precision, while fMRI studies make it possible to characterize neural responses across many different sounds and participants. The project develops improved statistical methods to isolate neural populations selective for singing and differentiate them from nearby neural populations that respond selectively to speech and music. The project uses computational audio methods to manipulate the melodic, rhythmic, and speech content of singing and then fit “encoding models” to determine how these different features of song are represented in different neural populations. Through these techniques, the project fundamentally improves the understanding of how human cortex encodes and processes song as a unique auditory stimulus. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-08

PROJECT SUMMARY The vast array of genetic elements within a bacterial genome dictates its potential to cause disease. These elements influence virulence, antibiotic susceptibility, and the ability to evade the immune response. Understanding and manipulating these genetic components are crucial for identifying the drivers of bacterial pathogenicity. However, a significant challenge arises because efficient genetic systems are typically limited to laboratory-adapted strains. This limitation leaves many virulent clinical pathogens genetically intractable. To address this challenge, we developed a genome editing platform on phage recombinase that works across a broad range of species. Editing bacteria with phage recombinases, a process termed recombineering, has been transformative in E coli. However, its reliance on host factors causes species-specificity that has limited its broader impact. We discovered a phage protein that is conserved across bacterial phyla that can used to identify broadly functioning phage recombinase systems. Leveraging this protein, we developed a recombineering system that operates in both Gram-positive and Gram-negative bacteria. To further explore the potential of phage-based genetic engineering, we have established a high-throughput selection to identify phage recombinases from genomic material without relying on homology to existing recombinases. Coupling the ubiquity of recombination modules in dsDNA phages with the vast diversity of genetic information encoded by phage, we anticipate identifying numerous new phage-based recombination systems. Initial results have demonstrated levels of genetic editing in the important human pathogen Staphylococcus aureus comparable to recombineering in E coli. This work will transform the way we genetically manipulate bacteria, enabling us to directly probe the genetic elements driving pathogenicity in clinically relevant strains.

NIH Research Projects · FY 2026 · 2024-08

Project Summary/Abstract The neural circuits associated with encoding odors in patterns of activity throughout the brain are critical not only for chemosensory perception, but are intimately linked to emotion, learning and memory in humans and mice, the major animal model for studying disorders that impact chemosensory function. We propose to study the circuit between the ventral CA1 (vCA1) region of the hippocampus and the main olfactory bulb (MOB) to between understand how cognitive aspects of behavior, such as a sense of environment, or anxiety can influence the encoding of chemical signals. Improved understanding of these circuits could provide critical insight into the link between chemosensory function and neurological, neurodegenerative, and neuropsychiatric disorders. Mitral and tufted cells (M/T) are the principal neurons of the main olfactory bulb (MOB) in rodents, and relay chemosensory information they receive to a number of cortical regions including the anterior olfactory nucleus (AON) and the piriform cortex. Rather than active as passive relays of this information, mitral and tufted cell activity is reshaped in part by local inhibitory interneurons and by extensive feedback projections from a number of areas including olfactory cortex and the hippocampus. We have recently begun exploring the structure of one of these feedback circuits, projections from the pyramidal cells of the ventral CA1 (vCA1) region of the hippocampus. Although these connections were identified nearly a ½ century ago, little is known about their function. In this proposal, we will investigate the overall hypothesis that vCA1 projections relay behaviorally relevant cognitive information (representing where the animal is, the anxiety associated with that location in the environment, etc.) to the MOB. Using a combination of electrophysiology and behavioral measures, we will ask three critical questions about the vCA1->MOB circuit. (1) What behavioral information do the vCA1 neurons that project to the bulb encode? (2) What are the synaptic networks that link vCA1 to the M/T cells in the bulb? (3) What if any of these behavioral features are represented in the bulb and how does this affect chemosensory processing? Combining these studies will provide critical insight into the circuits that allow behavior to shape chemosensory perception.

NIH Research Projects · FY 2024 · 2024-08

Abstract The goal of this R21 project is to develop an in vitro salivary gland Sjögren’s syndrome (SS) tissue chip (SSTC) platform based on microbubble array technology using the MRL/lpr mouse model. SS is an autoimmune disease characterized by sialadenitis (lymphocytic infiltration) in the salivary glands resulting in xerostomia (dry mouth). The disease commonly diagnosed in older women suggesting hormones may contribute to the pathogenesis. Estrogen and androgen receptors are expressed in the salivary gland and on the infiltrated lymphocytic cells. The proposed SSTC will be used to investigate the effect of in vitro and in vivo exposure to a mixture of endocrine disrupting chemical (EDCs) on the growth and function of salivary gland tissue mimetics (SGm). RNAseq studies will be performed on salivary glands to identify differentially regulated gene/pathways associated with sialadenitis and to discover if oral EDC exposure contributes to disease pathogenesis. This project will develop the first ever SSTC that can be used for mechanistic studies and future high throughput drug discovery studies. Currently there are no disease modifying drugs to treat SS patients.

NIH Research Projects · FY 2025 · 2024-08

PROJECT SUMMARY/ABSTRACT The female reproductive tract (FRT) microbiome consists of all microbes within that space, including the bacteriome and the virome, which is comprised of the phageome (bacteriophages) and eukaryotic viruses. Low diversity Lactobacillus-dominant bacteriomes play a pivotal protective role in maintaining women’s health, including preventing pre-term birth, bacterial vaginosis (BV), yeast infections, and sexually transmitted infections. However, shifts to high diversity FRT bacteriomes, such as in BV, result in increased FRT inflammation, and consequent increased risk of symptomatic BV, pre-term birth, and STIs including HIV. Bacteriophages are natural predators of bacteria and are more numerous and diverse than bacteria and may serve to regulate bacterial populations. Our prior work showed the FRT bacteriophages form communities which corresponded with FRT diseases; however, the mechanisms behind bacteriophage contribution to regulating FRT bacterial populations is largely undetermined. Our main objective is to determine the how these phageome communities contribute to FRT health by regulating alterations in the bacteriome. In this proposal, we will utilize metagenomic sequencing on FRT samples from a unique longitudinal cohort comprised of US women living with HIV and AIDS compared to healthy controls to investigate (Aim 1) the FRT phageome communities over time, (Aim 2) the impact of AIDS and antiretroviral therapy on the phageome, and (Aim 3) identify predictive taxonomic and metagenomic biomarkers of shifts to high diversity FRT bacteriomes using bioinformatic knowledge gained during my career development plan. My long-term career goal is to become an independently funded physician scientist leading a translational research team to elucidate the virome’s influence on human health and disease and to develop novel strategies to mitigate disease. My career development plan lays out a detailed strategy to augment my expertise in computational biology and microbiome biostatistics, with the overall goal to improve my viral and bacterial metagenomic pipelines, including functional annotation. An improved understanding of bacteriophage- bacterial interactions in the FRT including biomarkers predictive of pathogenic FRT shifts, will pave the way toward novel preventative strategies and phage-based therapeutics for FRT diseases including BV and STIs, thereby improving women’s reproductive health.

NIH Research Projects · FY 2024 · 2024-08

Project Summary: Most men diagnosed with prostate cancer (PCa) are 65 years of age or older. Radiotherapy (RT) is an effective and curative treatment for early-stage PCa. However, 20% of PCa patients can develop late, often irreversible, chronic adverse side-effects after their RT. Radiation cystitis (RC) is a clinically significant chronic toxicity. Symptoms of RC include hematuria and urinary dysfunction, including increased urinary frequency and urgency, incontinence, and dysuria, and these can be significant clinical concerns for the ~3.1 million PCa survivors in the US. These symptoms can be more pronounced in older PCa patients because of preexisting urinary symptoms and/or reduced functional reserve, putting them at increased risk of dysfunction after RT induced injury. RT dose-volume constraints are used to lower the risk of developing a treatment-related toxicity, but the bladder cannot be avoided completely in the PCa RT treatment plans, and significant variation in the incidence and severity of RC exists amongst PCa patients which suggests an important role for host factors personal to each PCa patient. The urinary microbiome is altered in urologic diseases common in older adults, and dysbiosis has been linked with urinary dysfunction unrelated to infection. But, no studies have investigated the effect of RT on the urinary microbiome, or the effect of dysbiosis on RC, among PCa patients. Therefore, we hypothesize that RT-mediated urothelial damage in the bladder that leads to disruption of routine urinary function, and increases urinary frequency, will produce urinary microbiome dysbiosis, and therefore microbiome dysbiosis could be a non-invasive urine-based early biomarker of RC. Our clinical genetic studies identified signaling pathways linked to the microbiome and immune cell recruitment that support this hypothesis. Using banked urine from our prospective clinical study of RC with up to 5 years of follow-up, as well as our preclinical mouse model of RC, we have demonstrated we can detect a urinary microbiome despite the low abundance, and we show evidence of dysbiosis after RT. This project will use banked urine from our clinical study to test the hypothesis that (i) the microbial composition and/or metabolic potential of the urinary tract is changed by RT, and (ii) dysbiosis and/or metabolic dysregulation will correlate with patient reported outcomes (PROs) capturing bladder dysfunction following RT. Then, using our mouse model of RT-induced bladder injury, we will test the hypothesis that (iii) changes in the microbiome may serve as a potential biomarker of RT injury to the urothelium, and if changes in microbiome are a response to tissue injury and recruited immune cells. This will be achieved by comparing dysbiosis with functional micturition, and local and systemic biomarkers of bladder injury, after focal RT to the entire bladder volume or just bladder trigone. Finally, using banked urine from both our human and mouse studies, we will evaluate whether a mitigator if radiation-induced bladder injury (angiotensin converting enzyme inhibitors) exerts its protective effect by altering inflammatory and immune processes thereby avoiding dysbiosis.

NIH Research Projects · FY 2025 · 2024-08

ABSTRACT/SUMMARY Radiotherapy (RT) is an effective treatment modality for pelvic malignancies. However, radiation cystitis (RC) is a widely recognized irreversible and chronic condition reported in 8-11% of cancer patients treated with pelvic RT. The symptoms of RC can include hematuria, increased urinary frequency and urgency, incontinence, and dysuria. Few effective treatments exist to alleviate these adverse symptoms, and there are no FDA approved preventative agents. Hyperbaric oxygen therapy does alleviate some symptoms, but its use is restricted by inaccessibility, cost, and contraindications, leading to poor patient compliance. The ill-defined pathophysiology and mechanisms of RC thwart the development of new therapies. Our GWAS in six large prostate cancer (PCa) RT cohorts identified SNPs, tagging AGT, correlated with patient-reported hematuria, a defining symptom of RC. AGT encodes angiotensinogen, part of the renin-angiotensin system (RAS). Our subsequent multi-site clinical study supports the hypothesis that angiotensin-converting enzyme inhibitors (ACEi) are radioprotective in the bladder; RC was seen in 16.5% of patients not taking an ACEi vs only 4.8% of those taking an ACEi during RT (p=0.01). In the same clinical cohort, release of extracellular vesicles into the urine (uEVs) and increased circulating levels of the pro-inflammatory chemokine CCL2 were significantly associated with symptoms of RC. In our murine model, ACEi protected against micturition changes, immune cell recruitment, and urothelial injury after RT. Based on these data, we hypothesize that RAS modulation and preventing CCL2-dependent immune cell recruitment will prevent bladder injury after RT. Our objectives are to characterize and investigate the mechanistic role of RAS and its pharmacologic modulation in tissue inflammation and injury in the bladder after RT and develop a urine-based biomarker of clinical RC. Our four specific aims use a combined preclinical and translational approach: Aim 1: To characterize mechanisms of bladder inflammation and immune cell recruitment in the development of bladder injury after single dose and fractionated RT, as a function of dose and irradiated volume; Aim 2: To determine optimal duration of ACEi or angiotensin receptor blockers (ARBs) to elicit maximal radioprotection, and the mechanism of prevention of progressive bladder injury, and determine the therapeutic ratio using an orthotopic PCa model; Aim 3: To assess bladder uEV release kinetics by nanoparticle tracking analyses as a predictive biomarker of RT injury, and characterize EV cargo proteins and functional ability to induce cellular stress/damage response in our mouse models; and Aim 4: To validate uEV kinetics as a biomarker of late RC, and predictor of RAS modulator response, using biosamples in two clinical studies of men receiving RT for PCa. An EV biomarker could be used to identify patients needing early mitigating interventions, such as an ACEi, to avoid progression to severe RC.

NIH Research Projects · FY 2024 · 2024-08

Valvular Heart Disease (VHD) encompasses a number of common cardiovascular conditions that account for 10% to 20% of all cardiac surgical procedures in the United States. A better understanding of the heart valvular disorders and underlying molecular mechanisms is important to aid in the management and treatment of patients with VHD. Endothelial mesenchymal transition (EndMT) is a complex biological process in which endothelial cells progressively evolve into cells with a mesenchymal phenotype. EndMT plays an essential role in cardiac valve formation and function, and EndMT is temporally and spatially regulated during organ development and maintenance. Abnormal EndMT is critically implicated in the pathogenesis of both congenital cardiac valve disease and late-onset cardiac valve dysfunction. Thus, further understanding exact molecular pathways that control EndMT during cardiac valve development and maintenance is likely to be significant in order to develop therapeutic strategies to ameliorate heart valve disease. It has been well-established that vascular endothelial growth factor (VEGF), one of the most potent regulators of angiogenesis, also plays a key role in control of EndMT during cardiac valve development. A series of our previous studies have demonstrated that a newly discovered serine/threonine protein kinas family members of protein kinase D (PKD), are key signal molecules in mediating VEGF signaling and function. The nascent data from our recent preliminary studies suggested a key role of protein kinase D3 (PKD3, gene name Prkd3) in regulation of EndMT and VHD. In current application, we will determine how PKD3 regulates EndMT and heart valve development, physiological function and pathological changes, and how to manipulate the PKD3-dependent signaling pathways to prevent excessive EndMT and cardiac valve enlargement, ultimately, leading to new approaches to treat VHD. Upon completion of the proposed studies, it will have significant impact on our understanding of EndMT and cardiac valve development and function, and provide valuable information on the underlying molecular mechanisms of cardiac valve development and abnormal factors for VHD, which will help to design new therapeutic strategies for combating VHD. Recently, as part of the National Heart, Lung, and Blood Institute (NHLBI)’s implementation of the Cardiovascular Advances in Research and Opportunities Legacy (CAROL) Act, NHLBI issued a Notice of Special Interest to seek R01 applications that propose research in valvular heart disease (NOT-HL-23-079). Thus, our work is extremely important and highly relevant to NHLBI’s mission to elucidate the pathophysiology of VHD and to reduce the burdens of human heart disease.

NIH Research Projects · FY 2023 · 2024-08

Project Summary/Abstract Despite recent advances in pharmacological therapy and patient care, cardiovascular disease (CVD) remains a leading cause of morbidity and mortality. Salt-induced hypertension (SH) is a major form of human primary hypertension, which is the main risk factor for CVD. This proposal is designed to elucidate neural mechanisms underlying SH, with a focus on uncovering novel mechanisms involved in activating the brain (pro)renin receptor (PRR) and renin-angiotensin system (RAS). Accumulating evidence underscores the importance of neural mechanisms in SH, especially the centrality of brain RAS activity in the lamina terminalis and the paraventricular nucleus (PVN) of the hypothalamus. We recently reported that up-regulation of the PRR in the PVN is responsible for increased angiotensin II production, activation of the brain RAS and the development of SH, suggesting that the PRR is a key link in the chain leading from high-salt intake to brain RAS activation. However, how a high-salt diet up-regulates the brain RAS and PRR remains unknown. Our central hypothesis is that high salt up-regulates the brain PRR through an epithelial sodium channel (ENaC) and reverse mode Na+/Ca2+ exchanger (rNCX)–coupled signaling pathway, and modifies the central nervous system epigenetically, leading to the development of SH. To test this hypothesis, we will employ two commonly used mouse models of experimental SH, in conjunction with innovative techniques, including ex vivo live Ca2+ imaging, ground-state depletion followed by individual molecule return (GSDIM) super-resolution microscopy, cell-specific PVN targeting, and telemetry recording of phenotypes in vivo. Our objectives are to define the molecular signaling events that lead to regulation of the brain RAS and to establish the functional significance of epigenetics in SH. The following specific aims are proposed to address these objectives: (1) to test the hypothesis that formation of ENaC-rNCX–coupled subcellular Ca2+ microdomains is responsible for up-regulation of the neuronal PRR in salt-induced hypertension, and (2) to test the hypothesis that H3K4 trimethylation of the PRR promoter is crucial for the development of salt-induced hypertension. The proposed research is conceptually innovative and highly significant because it will resolve the enigma of how high salt intake activates the brain RAS and epigenetically modifies the PRR, leading to the development of SH. Successful completion of this proposal will establish molecular mechanisms of SH involving brain RAS activation and provide mechanistic insight into the epigenetics of hypertension.

NIH Research Projects · FY 2025 · 2024-08

More than 20% of laboratory tests in the intensive care unit are medically unnecessary. Laboratory overutilization contributes to reduced care quality and adverse complications including iatrogenic anemia. Multiple medical societies have highlighted the urgent need to address this problem, but the vast majority of interventions in the literature are quality-improvement initiatives with poor generalizability. The literature is even sparser in the highly vulnerable pediatric population, who are more susceptible to iatrogenic anemia given their smaller blood volumes than adult patients. With the rapid expansion of electronic health records (EHRs) and the development of massive clinical databases, machine learning (ML) has become a promising tool that can address the problem of laboratory overutilization. While few models have been developed to predict laboratory results in adults, among pediatric patients model development is extremely limited. Furthermore, very few predictive ML models in any clinical domain are translated into usable clinical decision support (CDS). Despite strong recommendations from nearly all best practice informatics resources, most CDS implementations rely on “out-of-box” deployment rather than employing user-centered design principles. This can leave burdensome, sometimes harmful systems in place without demonstrated effectiveness. This staged-award proposal will leverage the PICU Data Collaborative (PDC), a multicenter collaboration of pediatric intensive care units (PICUs) across the United States, to develop ML-based CDS to predict future laboratory values for the purpose of reducing laboratory overutilization. In the R21 phase, ML models will be trained on 188,000+ unique PICU patient encounters in the PDC database to forecast future laboratory values (Aim 1). Concurrently, guided by the Practical Robust Implementation and Sustainability Model (PRISM) framework, contextual factors will be identified to inform an ML-based CDS implementation within the PICU sociotechnical environment. In the R33 phase, new a priori identified features will be incorporated to enhance the ML models developed in Aim 1. These retrained models will be silently evaluated on prospective data from selected PDC sites. In Aim 4, an EHR-embedded CDS tool will be designed for a selected PDC site, incorporating user-centered design principles informed by the results of Aim 2. The final ML model from Aim 3 will then be deployed in a pilot study at the single site, where we will measure the implementation outcomes of reach and adoption. The result of this work will establish a useful, usable CDS tool to reduce laboratory overutilization based on multicenter data and framed in the PICU contextual environment. Our pilot deployment will establish the groundwork for a future effectiveness-implementation hybrid multicenter trial. These processes will be generalizable and serve as a blueprint for developing data-driven translational decision support tools that can be adapted to a variety of diverse healthcare settings and subsequently reduce disparities.

NSF Awards · FY 2024 · 2024-08

Long-duration energy storage (LDES) technologies provide numerous societal benefits, including enhancing grid stability, enabling greater use of renewable energy, and reducing the dependence on fossil fuels. LDES technologies transform intermittent renewable resources, such as solar and wind power, into dispatchable power sources. Among the available options for LDES are redox flow batteries (RFBs), which store energy electrochemically and feature significant operational flexibility, modularity, and cost advantages. Nonetheless, key challenges remain in developing energy carriers for RFBs, including cost and performance barriers stemming from fundamental limitations in their chemical properties. This research will focus on designing new chemical compounds, called biphasic charge carriers, that can store electric power, and link the fundamental chemical properties of these charge carriers to their function in small-scale working batteries. The goal is to develop a clear set of design principles for a new generation of batteries purpose-built for storing solar and wind power. This research project integrates hardware prototypes under active development by a startup company founded out of one of the participating laboratories, enabling further potential for societal impacts through commercialization and entrepreneurship. Additionally, a new training curriculum for undergraduate students will be developed to learn the fundamentals of electrochemistry and battery science. Work will be undertaken to deploy a series of educational outreach activities encompassing the development of low-cost hardware and software tools to support broader dissemination via the delivery of new laboratory courses at the participating universities, education research literature, and digital media. This project will develop design rules for inorganic charge carriers for redox flow batteries. The overarching objective is to overcome hurdles related to energy density and materials availability by developing redox-active molecules that store charge both as soluble units and in the solid phase. This feature opens opportunities to explore new RFB designs, beyond aqueous transition metal complexes, via the development of biphasic charge carriers, wherein soluble forms of a given molecule are used as mediators to shuttle charge to or from the solid form of the same molecule. The project encompasses hypothesis-driven studies directed at controlling molecular solubility across multiple charge states via ligand modification, alongside detailed investigations of charge transfer at interfaces between the electrode and the electrolyte and between the electrolyte and the solid-state charge carrier. Successful completion of this work will yield lab-scale biphasic battery systems with promising functional properties that can be fully rationalized from basic physical properties, entailing extensive opportunities for further development. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

Ignacio Franco of the University of Rochester is supported by an award from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry to develop the theory and simulation of the emergent properties of matter when driven or “dressed” by lasers. Characterizing and controlling matter driven far from equilibrium by lasers represents a key challenge for science and technology. This is because matter can behave very differently when shaken by the intense coherent light provided by lasers. Further, lasers offer the possibility of manipulation on an ultrafast timescale (on the order of a millionth of one billionth of a second), something that is simply not achievable by more conventional means such as an applied voltage, chemical or thermodynamic control. The Franco group will develop general schemes for the laser control of electrons in matter and, in doing so, catalyze the development of a novel class of laser-dressed dynamical materials with effective properties that are tunable “on-demand" on ultrafast time scales. For example, the group has pioneered schemes to use of light to drive ultrafast electronic currents and construct ultrafast logic gates that now enable information processing at the fastest time scales allowed by nature. In addition to its interest at a fundamental level, manipulating electron dynamics with lasers is the basis for the development of ultrafast electronics, switching, imaging, catalysis, and, in fact, any science and technology at large based on electrons and their control. The outreach activities of this proposal include the organization of annual conferences exploring quantum frontiers in molecular science, integrating research with education by developing a graduate course on “Quantum Dynamics”, and advancing initiatives to increase diversity in STEM at the University of Rochester. Specifically, the Franco group will investigate the fundamental limits in the quantum control of electrons and advance our capabilities to use intense ultrafast laser pulses to manipulate electronic properties and dynamics in nanostructures and extended systems. The general objective is to understand the ability of laser-dressed matter to absorb light, transport charge, and the use of light to control electron dynamics. For this the group will develop: (a) A Floquet theory and simulation scheme of the optical absorption properties of realistic laser-dressed solids as needed to make experimentally testable predictions and stimulate experimental progress. (b) The theory and simulation of the emergent field of petahertz electronics where strong few-cycle laser pulses are used to trigger femtosecond currents along nanoscale junctions. In particular, we aim at clarifying the role of the electrodynamic propagation of light in this complex electromagnetic environment in the current generation. (c) A practical scheme to capture radiation-matter interactions beyond the dipole approximation while avoiding cumbersome multipolar expansions. We will use it to quantify the influence of the spatial structure of light in nanojunctions in (b). The project will train 2 Ph.D. students in state-of-the-art methods in quantum dynamics and light-matter interactions. All codes developed as part of this project will be made available for general use through GitHub, impacting the ability of the broader scientific community to model strong light-matter interactions. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

This award supports an effort to understand the complexities of turbulence in high energy density plasmas, a phenomenon with direct connections to many fields of science such as astrophysics and space physics. Turbulent astrophysical flows are observed to be cohesive across vast distances, and by mimicking similar plasma conditions in a laboratory this project aims to characterize plasma turbulence across different scales. The insights gained within the project may enhance technologies critical to national defense and energy security, such as nuclear stockpile stewardship, fusion energy development, and advanced propulsion systems. The project will also engage students from the University of Rochester and local high schools with predominantly underrepresented minority populations through an innovative outreach program. This program, modeled as an after-hours math club with role-playing elements, will foster practical problem-solving skills and mentorship. Plasma turbulence is known to lead to self-organized spinning flows and rapid transport across multiple scales. In astrophysical plasmas, electromagnetic fields mediate long-range interactions, maintaining cohesive flows across distances spanning light-years. This project aims to measure magnetohydrodynamic (MHD) turbulent spectrum down to the viscous scale in a magnetized high energy density plasma created within the HADES pulsed power facility at the University of Rochester. Using advanced interferometry and imaging diagnostics, the project aims to correlate turbulent eddies across multiple scales and to evaluate the extension of turbulent scales by magnetic fields. Project's findings will allow theorists to validate MHD turbulence models and will help to better estimate the impact of turbulence on transport, including anomalous heat conduction, magnetic field diffusion, and stability conditions for flows with high Reynolds numbers. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

This award will support The NY 2024 RNA Meeting in the Finger Lakes to be held on October 13th-15th, 2024. The meeting will include participants from a wide range of career stages and research areas, including undergraduates, graduate students, postdoctoral fellows, principal investigators, and scientists in the biotechnology industry. It will be organized through the joint efforts of the Center for RNA Biology at The University of Rochester and the RNA Institute at The State University of New York at Albany. The meeting provides an opportunity to bring together leaders in the field of RNA biology with new investigators and trainees at multiple career levels to present, discuss, and disseminate their work. The conference affords a rich opportunity for broader impacts on the community through (i) participation of diverse researchers, including from groups underrepresented in STEM fields, (ii) advancement of STEM education, and (iii) development of a diverse and competitive STEM workforce by catalyzing partnerships between researchers in the academia and industry. The format of this meeting is designed to maximize attendee exposure to the frontiers of RNA biology through seminars from invited speakers on a range of topics, ‘lightning’ talks by trainees, an extensive poster session, and many opportunities for informal conversations. The meeting topics include nascent RNA metabolism, structural RNA biology, RNA in neuroscience, CRISPR biology, RNA therapeutics, and RNA vaccine development. Meeting participants will thus be immersed in a broad swath of contemporary interests driving RNA biology both in academia and the biotechnology industry. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.