University Of Rochester

NIH Research Projects · FY 2026 · 2025-05

Project Summary/Abstract This resubmitted R21 proposal is in response to the Notice of Special Interest (NOSI): Xylazine: Understanding Its Use and Consequences, NOT-DA-24-012. The goal of this study is to determine if xylazine and its metabolites act as agonists or positive allosteric modulators (PAMs) at the mu and kappa opioid receptors (MOR, KOR). Additional studies will determine if xylazine and its metabolites are agonists, antagonists, or inverse agonists at the sigma 1 (s1R) and sigma 2 receptors (s2R). Xylazine binds with nM affinity to the sigma receptors. Illegal drugs, particularly fentanyl and stimulants, are being mixed with xylazine to enhance drugs effects or increase street value by increasing weight. Xylazine is not approved for human use. Xylazine is historically regarded as an α2-adrenergic receptor agonist based on physiological studies using α2-adrenergic receptor antagonists. However, a recent studies showed that the opioid antagonist naloxone induced withdrawal from xylazine in mice and xylazine had micromolar affinity for the α2-adrenergic receptor. Our preliminary data shows that xylazine had a Ki value of 330 ± 13 nM for inhibiting binding to the human KOR. Xylazine also inhibited forskolin-induced cyclic AMP levels in CHO cells expressing the human KOR and stimulated G protein activity as measured by a BRET assay. The following Specific Aims will characterize the potency and pharmacological properties of xylazine. Aim 1 will determine if xylazine and its metabolites act as PAMs at the MOR and KOR as shown with G protein and β-arrestin signaling. Bias signaling through the six Gαi/o/z proteins will be determined and compared with results obtained with β-arrestin recruitment. In addition, experiments will determine if xylazine and its metabolites inhibit forskolin-stimulated cAMP as an agonist or as a PAM. Radioligand binding experiments will determine if xylazine acts as a PAM by increasing the affinity of agonists such as fentanyl for the MOR or if xylazine increases the potency of an agonist in a functional assay by enhancing coupling of the receptor with the G protein or β- arrestin without affecting the affinity. Experiments will determine if the opioid receptor PAM BMS986122 will increase the potency of xylazine at the KOR and MOR. Xylazine binds to s1R and s2R with Ki values of less than 200 nM. The pharmacological properties of xylazine at the s1R and s2R are not known. The proposed experiments will use a BRET assay and cell proliferation assays to determine if xylazine and its metabolites are agonists, antagonists, or PAMs at the s1R and s2R. Collectively, this study will determine the pharmacological properties of xylazine and its metabolites, which may help explain physiological effects observed in people taking illegal drugs mixed with xylazine.

NSF Awards · FY 2025 · 2025-05

With support from the Chemical Structure and Dynamics (CSD) program in the Division of Chemistry, Professors David McCamant and Ignacio Franco of the University of Rochester will develop experimental and theoretical methods to study quantum decoherence in molecules that are excited with visible light. When a molecule absorbs light, it can be placed in two states at the same time, also known as a coherent superposition. These superposition states are short lived, fading away in less than 100 millionths of a billionth of a second, due to interactions of the molecule with its surroundings. Professors McCamant, Franco, and their students will perform sophisticated femtosecond time-scale laser experiments to understand how specific molecular motions contribute to this rapid decoherence process. These experiments will be interpreted in the context of theoretical models to learn how specific motions disrupt the electronic coherence. Their discoveries could improve our understanding of how to manipulate electronic coherence via molecular design, with the potential to guide future molecular-based quantum technologies. The project will provide research opportunities for graduate and undergraduate students, contributing to the creation of a quantum-enabled workforce. The proposed experiments will use Femtosecond Stimulated Raman Spectroscopy to reconstruct the spectral density of various families of organic dyes, and map decoherence pathways in molecules. The spectral density, which reveals the coupling of electronic superposition states in molecules to vibrations and solvent, can be measured by determining the Raman cross-sections of these vibrations and modeling the Raman intensities and absorption spectra with spectroscopic theories. The chosen molecular families -- oligoacenes, fluorescent dyes and molecules used as single-photon emitters for quantum information application -- will exemplify how the decoherence changes with molecular size, rigidity, chemical functionalization and temperature. The analysis will further reveal the dominant vibrational modes responsible for decoherence, an understanding that is needed to develop chemical strategies for modulating this property. Professors McCamant and Franco will also develop a new pathway for undergraduate chemistry majors that emphasizes quantum mechanics and physical chemistry early in their college curriculum. 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 2026 · 2025-05

The present proposal will utilize an animal model and in vivo imaging techniques to determine whether altered cell-specific activity or disrupted neurotransmitter signaling in the auditory and frontal cortices underlie tinnitus and hyperacusis perception. Tinnitus (i.e., ringing in the ears) and hyperacusis (hypersensitivity to sound) are two highly prevalent and often debilitating auditory conditions. At present, the neural basis of these conditions remain unresolved, which has significantly hindered our ability to develop effective treatment strategies for ameliorating their perception. Prior studies suggest that tinnitus and hyperacusis may arise as a consequence of a maladaptive imbalance between excitation and inhibition in the auditory cortex following hearing loss. Additionally, top-down gating of this aberrant auditory activity by higher-level brain regions, such as the frontal cortex, has also been implicated as a contributing factor to tinnitus/hyperacusis perception. However, we currently lack an understanding of how altered activity of specific neuron sub-types and changes in neurotransmitter signaling within the auditory and frontal cortices differentially contribute to the generation of tinnitus, hyperacusis, or both conditions. The present proposal will use a validated operant conditioning tinnitus behavioral paradigm co-developed by the PI and a sound-avoidance hyperacusis task, combined with advanced in vivo imaging techniques to advance our understanding of the neural basis for these auditory conditions. Using cell-specific calcium imaging via miniscopes, Aim 1 will investigate the contribution of altered pyramidal cell activity in the auditory and frontal cortices to tinnitus/hyperacusis perception. In Aim 2, fiber photometry recordings of neurotransmitter signaling in the auditory and frontal cortices will be used to determine whether altered glutamatergic/GABAergic signaling underlie perception of these auditory conditions. Ultimately, results from these experiments are expected to have high impact because they will identify potential cell-specific and neurotransmitter-specific therapeutic targets for treating tinnitus and hyperacusis perception. Dr. Sarah Hayes, Au.D., Ph.D. is a clinician-scientist dedicated to providing audiological care for patients with tinnitus and hyperacusis, and advancing our understanding of the neural basis for these disorders through her research. This proposal leverages her extensive experience in animal behavioral assessments of auditory disorders and electrophysiological recordings in rodents, to provide her with the opportunity to develop new skills in advanced in vivo imaging techniques, while moving the field forward in elucidating the neural basis for tinnitus/hyperacusis. Additionally, the technical expertise that she will acquire through this proposal will help establish a scientific platform for her to identify and assess therapeutic targets and treatments for tinnitus and hyperacusis. Collectively, the expertise of her mentorship/advisory team, combined with the vibrant collective of hearing, balance, and neuroscience researchers at the University of Rochester provides an ideal setting for Dr. Hayes to develop into a successfully funded independent investigator.

NIH Research Projects · FY 2026 · 2025-05

Over the recent sixty years, dental titanium implants have been almost universally accepted as a leading and safe system to replace lost and diseased teeth, largely due to the biological qualities of titanium to be seemingly inert to the body’s immune system. Yet, the increased longevity of patients with implants, the increased lifespan of implants within individual patients and the increased number of elderly patients with implants have exposed the number of implant failures as an everyday reality in clinical dentistry. Potential etiologic factors that contribute to peri-implantitis include oral plaque accumulation; titanium particle/ions released from dental implants, complications from implant surgery, and others. In our preliminary studies, we have successfully established a rat peri-implantitis model using immediate titanium implants in a rat mandible. We have used this model in our quest for potential mechanisms that explain peri-implantitis, including inflammation of the peri-implant environment, loss of bone and a dramatic increase in reactive oxygen species (ROS). Further studies uncovered an epigenetic mechanism through the SETD7-SFRP1-Runx2 pathway explaining titanium particle induced changes in implant bone homeostasis. Specifically, we demonstrated that both the methyltransferase Setd7 and the Wnt-inhibitor SFRP1 were upregulated in titanium-challenged PDL cells while both enrichment for H3K4me1 and Setd7 on the promoter of the SFRP1 Wnt inhibitor were increased. Together, these studies are geared to test the hypothesis that periimplantitis progresses as the result of an inflammatory microenvironment and oxidative stress and that this trend may be reversed through the application of epigenetic modulators.

NIH Research Projects · FY 2026 · 2025-05

Project Summary/Abstract A defining feature of the primate brain is its highly specialized organization: distinct brain areas support different functions. As a result, when an area is damaged, the brain may lose the functions for which the area was responsible. In some cases, these deficits can be compensated for through plasticity, but we know little about the principles, mechanisms, and consequences of functional reorganization in damaged brains. Here, we seek to address this gap by studying lesion-induced system reorganization in humans, marmosets, and macaques. We focus on damage to the primary visual cortex (V1), as a model system for studying cortical processing. V1 constructs a general-purpose visual representation by measuring the local distribution of orientation energy in the retinal input, informing the content of our perceptual interpretations of the environment as well as the confidence we have in these interpretations. V1 damage typically results in severely diminished orientation sensitivity and ability to evaluate its reliability. However, the lost perceptual capacity can be partially recovered, suggesting that V1 damage may be followed by a functional reorganization of the visual system. We will leverage the power of normative theory to establish the principles underlying system reorganization in idealized artificial visual systems trained to efficiently represent natural visual input. Guided by preliminary findings, we hypothesize that following V1 damage, extrastriate area MT becomes a primary node of visual connectivity and function and a primary cortical generator of orientation selectivity. Two subcortical routes of information transfer between the retina and MT make this possible: one via the lateral geniculate nucleus and the other via the pulvinar. We will use complementary methods in two species to establish the circuit mechanisms underlying system reorganization and the relative contribution of these two pathways. We will measure large-scale neural responses in MT in V1-damaged marmosets with genetically-encoded calcium indicators while selectively inactivating each subcortical pathway. We will also use state-of-the-art, 7T layer-fMRI to measure the laminar distribution and retinotopic specificity of orientation selectivity in area MT of humans with stroke-induced V1 lesions. To study higher-level, cognitive consequences of cortical damage, we will assess metacognitive judgments of confidence in perceptual decisions in the absence V1. A rich body of theoretical and empirical work suggests that perceptual confidence is directly informed by neural activity in sensory cortex. Damage to a sensory area may thus reduce metacognitive ability to evaluate the reliability of perceptual events. We will study the behavioral effects of V1 damage on metacognitive ability as well as its neural basis in human subjects using high-resolution 7T fMRI. Finally, we propose to develop an animal model of the reduction and recovery of metacognitive ability following the disruption of normal V1 function with macaque monkeys performing a recently developed perceptual confidence task. Together, this work will establish a foundation for studying the principles, mechanisms, and cognitive consequences of functional reorganization following brain damage.

NSF Awards · FY 2025 · 2025-04

Computer simulations are central to science and engineering activities across tasks as varied as weather prediction and electrical grid optimization. Simulation relies on numerical solvers whose continued improvements in terms of speed and accuracy are of pivotal national importance. Unfortunately, the progress of solvers is hampered by two emerging challenges: (1) the problems being modeled and solved, including their data captured through matrices, are becoming numerically harder, causing many solvers to fail; (2) newer arithmetic hardware, increasingly second-purposed from those developed to support artificial intelligence (AI), ends up having suboptimal precision while also deviating from established numerical standards. The project's novelties are: (1) the development of practical formal methods that are capable of capturing the correctness expectations of numerical algorithm designers as formal requirements; (2) the development of formal models capable of modeling non-standard hardware while bridging their behavioral differences to present uniform higher level formal abstractions; and (3) methods to carry out end-to-end correctness verification that help establish that the formal models of the underlying hardware meet the numerical algorithm correctness requirements. The project's contributions will help advance the nation's simulation-based scientific exploration capabilities. It will also help recoup the investments already made in today's numerical solvers, allowing them to be easily and reliably adapted to new problems and hardware. Without these capabilities, scientific computing and data-enabled discoveries can experience multiple productivity gaps, negatively impacting scientific research and engineering advances. The project will also train students to have the debugging skills necessary to solve numerical issues arising in the context of future solver design and deployment. This project handles data hardness using iterative refinement algorithms that are followed by the linear algebra routines underlying linear solvers. These algorithms can be verifiably guarded by novel formal properties that stem from how the problem eigenvalues appear in the problem’s data matrices. This project's techniques adapt the numerical hardware to pre-existing solvers (and their assumptions) and help develop new solvers that employ mixed numerical precision schemes during iterative refinement. These adaptations will be aided by novel emulation schemes that help match and formally verify numerical precision, rounding rules, and floating-point exception handling rules. The goals of these techniques are to resolve the "Data/Numerics Tug of War" so that each solver developer obtains their preferred starting point: from algorithms down to hardware or vice-versa. This project will contribute key scientific principles and algorithms to support future research and development activities in adapting solvers to newer hardware. It will have a broad impact, including (1) sustain established solvers across new generations of hardware and (2) solve numerical issues that arise when solvers and optimizers used in AI are enhanced to handle larger scale and newer 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 2026 · 2025-04

PROJECT SUMMARY/ABSTRACT Acid-sensing ion channels (ASICs) are a family of low pH-activated ion channels found throughout the central and peripheral nervous systems. ASICs are important players in several neurological conditions such as cell death following ischemic stroke, neurodegeneration, fear and anxiety and synaptic plasticity. ASICs are particularly important in various forms of pain like cutaneous nociception and inflammatory hyperalgesia. Consistent with this role, the subunits ASIC1a, ASIC1b and ASIC 3 are all found in dorsal root ganglia and trigeminal ganglia neurons from both human and rodent. Moreover, pain sensation can be reduced by pharmacological blockade of ASIC1, using the selective toxins mambalgin or psalmotoxin1, or inhibition of ASIC3, using the toxin APETx2. These effects are attenuated in mice where ASIC1 or ASIC3 have been deleted, further implicating these channels as important mediators of peripheral pain. Thus, ASICs – and in particular ASIC1a, 1b and 3 – are attractive targets for analgesic treatments. However, translational efforts have been complicated by several factors. In particular, the binding site for APETx2 on ASIC3 is unknown, preventing drug design efforts that exploit this toxin. Also, the ASIC1 inhibitor mambalgin acts differently in rodent versus human ASICs. While mambalgin inhibits rodent ASIC1b, thereby producing peripheral analgesia, it actually potentiates human ASIC1b. And finally, the physiological AISC targets are likely heteromers of these subunits that would be less sensitive to individual subunit specific toxins. Here we propose to overcome these challenges through two specific aims. First, we have identified a novel binding site for APETx2 based on computational docking and supported by experimental evidence. We will further test this novel site through a combination of patch clamp electrophysiology and surface plasmon resonance assays. Second, we will generate and test a series of novel bivalent toxins for inhibitory effect on heteromeric ASICs of defined stoichiometry using a concatemer system. Taken together, these proposed experiments may identify the long sought APETx2 binding site, generate a library of valuable heteromeric ASIC concatemers and test an array of novel bivalent toxins at these physiologically relevant heteromers. These toxins may serve as useful research compounds, either as functional modulators or specific markers when conjugated to fluorophores. Most importantly, we may identify toxin pairings to act as a peripheral analgesic leads for further development.

NIH Research Projects · FY 2026 · 2025-03

The mission of the Wilmot Cancer Institute (Wilmot) at the University of Rochester (UR) is to provide the highest quality treatment and care, through expert and innovative medicine, science, and education, for any patient burdened by any cancer within Central and Western New York, and beyond. Wilmot serves a distinct population in a catchment area of more than three million people confronted with a cancer incidence significantly above national averages, due to a disproportionately aging population, tobacco use, and predominantly poor urban and rural communities. During a 50-year history, Wilmot’s research has led to changes in oncology standards of care and paradigm-shifting discoveries, including the science behind the HPV vaccine. Wilmot investigators are respected internationally as leaders in cancer control and supportive care research, and Wilmot’s extraordinary expertise in this area has been recognized through a longstanding National Cancer Institute (NCI)-funded National Community Oncology Research Program research base award. Wilmot also benefits from outstanding visibility and strength in hematological malignancy clinical and translational research. Wilmot has created three transdisciplinary research programs (Genetics, Epigenetics and Metabolism; Cancer Microenvironment; and Cancer Prevention and Control), with a unifying research theme of “aging and cancer”. Wilmot members continue to push the frontiers of cancer science: identifying bone marrow microenvironment characteristics that support myelodysplastic syndrome; defining the role of geriatric assessment in medical oncology; harnessing the innate immune system to attack pancreatic cancer; and discovering mediators of cancer resistance and novel cancer cell vulnerabilities with promise for therapeutic translation. Attention to Wilmot’s 27-county catchment area through prevention services and research is achieved with bidirectional collaboration via a robust Community Cancer Action Council and associated Research Advisory Committees. Major institutional investments include space, senior scientists, junior faculty recruitment, and a clinical trial infrastructure resulting in Wilmot being a designated Lead Academic Participating Site of the National Clinical Trials Network. With support of the UR, the community, and a P30 Cancer Center Support Grant, and under the leadership of Director Jonathan W. Friedberg, MD, MMSc (CM), Wilmot will: 1) improve patient outcomes through paradigm-shifting, transdisciplinary discovery, integrating basic, translational, and population science; 2) translate basic and population science discoveries to benefit patients through interventional clinical trials; 3) enhance mentoring and career development in cancer science for researchers at all career stages through interdisciplinary curricula; and 4) engage communities in the Central and Western New York catchment area to uncover unmet needs and implement responsive cancer prevention, community-driven research, dissemination efforts, and education programs. Wilmot’s Strategic Plan guides all of these activities.

NIH Research Projects · FY 2025 · 2025-03

PROJECT SUMMARY: Carefully calibrated responses of lung resident leukocytes and lung epithelial cells are essential to meet the conflicting demands of protecting critical gas exchange surfaces from pathogens (resistance) while preventing unrestrained inflammation and promoting repair (resilience). The overall premise of this application is that lung resistance and resilience pathways are remodeled by neonatal colonization by commensal microbiota, contributing to poor lung health and chronic respiratory disease beyond infancy. Infancy represents a critical ontogenic window when evolving microbial communities colonizing the infant potentially program lung homeostasis. This paradigm is exemplified by epidemiological observations linking perturbations in the microbiota (dysbiosis) due to antibiotics (ABX), a regrettably common occurrence in pediatric clinics, is associated with increased severity of viral respiratory tract infection (RTI), increased need for hospital admissions, and the development of chronic inflammatory diseases that commence during infancy, reemphasizing the need for novel therapies to support this vulnerable population. Published and preliminary data from my laboratory show that disruption of commensal colonization during the perinatal window disrupts the accrual, functional competence, and long-term fate of lung resident leukocytes and interrupts the epithelial cell differentiation program. Fecal transfer can correct some of these deficits and improve clinical outcomes in murine and primate models. Nevertheless, a unifying framework explaining how early-life dysbiosis remodels the developmental program in the tissue-resident lymphocyte-epithelial cell homeostatic unit remains unresolved2. Knowledge of specific taxa essential for lung homeostasis and the critical window during which this microbiota program the lung homeostatic pathways remain undefined. Addressing these essential gaps of knowledge is a key objective of the proposed R35 program. This application explores the concept that dysbiosis interrupts the accrual and long-term fate of lung-resident CD8+ T cells [Theme 1: Resistance] and reprograms the regenerative pathways in the alveolar epithelial cells [Theme 2: Resilience]. We will explore the therapeutic potential of specific microbiota to mitigate these deficits and decrease severe LRTI during infancy [Theme 3: Remediation].

NSF Awards · FY 2025 · 2025-03

This project will restore a critical scientific instrument at the University of Rochester. The instrument, known as a laser ablation inductively coupled plasma mass spectrometer (LA-ICP-MS), allows scientists to precisely measure tiny concentrations of elements in rocks and minerals. Bringing this instrument back to full working order ensures that researchers can continue investigating how Earth’s crust formed and evolved, as well as how essential resources and minerals concentrate in certain regions. These discoveries are not only vital for advancing scientific understanding of Earth’s past, but also for informing the sustainable use of natural resources and promoting science education. In addition, using the instrument in undergraduate teaching labs will allow students to gain hands-on research experience and develop critical skills for future careers in science. The primary goal of this project is to repair the software, computing hardware, and laser components of the LA-ICP-MS system, with the goal of extending its useful lifespan by a decade. The restored instrument will support several active NSF-funded research initiatives at the University of Rochester’s Early Earth and Experimental Geochemistry Laboratory. These initiatives include studying the geochemical signatures of ancient impact melt sheets to understand Earth’s early crust formation, investigating the cycling of halogen elements over geologic time, and identifying regions with the potential to host critical mineral deposits essential to modern technologies. To achieve these objectives, degraded computer and control software components will be replaced, the laser head and related hardware will be repaired, and the system will be recalibrated to ensure stable, reliable operation. With these improvements, the LA-ICP-MS will again provide high-precision isotopic and elemental data of natural and experimental samples, and enhance educational experiences for both graduate and undergraduate students. 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 2026 · 2025-03

Vision is active—we move our eyes to acquire information and to track objects of interest. However, eye movements have visual consequences; for example, when we smoothly move our eyes to pursue an object of interest, this adds components of motion to the retinal image. These visual consequences of eye movements must be compensated to judge how objects move in the world. The conventional view is that compensation for smooth pursuit eye movements can be achieved by subtracting a vector (equal and opposite to the eye movement) from retinal image velocity. We demonstrate that this conventional view has limited applicability, and that even a simple combination of eye translation and rotation has visual consequences that cannot be compensated by a vector subtraction. Crucially, this means that the brain needs to infer the viewing geometry (defined here as how the eye translates and rotates relative to the scene) and then perform different computations to estimate the motion and depth of objects during pursuit eye movements, depending on the viewing geometry. We develop a theoretical framework that predicts how perception of object motion and depth should depend on viewing geometry. In Aim #1, we use human psychophysics to test our theoretical predictions. Preliminary data show the perceived motion and depth have perceptual biases that depend strongly on viewing geometry, as predicted by our theory, even while the retinal velocity of the judged object remains fixed. These biases occur automatically, without training or feedback. In Aim #2, we test whether neural activity in passively fixating monkeys is influenced by viewing geometry (without training) in ways that can account for perceptual biases. In Aim #3, we measure both behavioral and neural effects of manipulating viewing geometry to assess whether neural modulations in different visual areas (MT, MSTl, and VPS) can account for the observed perceptual biases. Our strong preliminary data suggest that we will make important advances in understanding how inferred viewing geometry interacts with neural computations of motion and depth. The proposed research is directly relevant to the research priorities of the Strabismus, Amplyopia, and Visual Processing program at the National Eye Institute.

NIH Research Projects · FY 2026 · 2025-03

Parkinson’s disease (PD), Lewy Body Dementia (LBD) and related disorders are the second most common neurodegenerative illness affecting over 1.5 million Americans and are the 14th leading cause of death in the United States. Notably, while PD is traditionally described by motor symptoms (e.g. tremor), more recent research demonstrates that nonmotor symptoms such as pain, depression, and dementia are leading causes of mortality, diminished quality of life, nursing home placement and caregiver distress. There is significant evidence that many of the needs most important to patients and family are poorly addressed under traditional care models and that palliative care—an approach to caring for individuals with serious illness that addresses multiple causes of suffering including medical symptoms, psychosocial issues and spiritual needs—may improve relevant patient and caregiver-centered outcomes. Unfortunately, progress in this field threatens to increase rather than diminish disparities in care. While mounting research shows palliative care improves outcomes in PD, these studies have largely failed to reach or include underserved populations. Studies to date have not dedicated sufficient resources to counter known disparities in neurologic and palliative care, nor have they utilized appropriate community engagement methods to overcome key barriers. This R34 planning grant represents the first step of community-based and engaged research to develop and assess culturally-tailored approaches to improve the reach of palliative care research for neurodegenerative illnesses and will lay the groundwork for future community-engaged clinical trials. The current proposal reflects ongoing work from a multidisciplinary team composed of academic and community members to explore how to modify current models of palliative care in PD to be culturally sensitive, accessible, scalable, and integrated into current healthcare institutions and systems serving the Black/African American and Hispanic communities. Notably, interest in this research topic was generated by our community advisory board and reflects their perception of pressing gaps in neurologic and palliative care services. Our Specific Aims are to: 1) Strengthen existing academic-community collaborations centered on palliative care for PD and LBD in Black/African American and Hispanic through principles of Community-Based Participatory Action Research (CBPAR); 2) Conduct qualitative assessments within the CBPAR model to identify the most important palliative care needs of Black/African American and Hispanic communities, information gaps, and preferences for receiving supportive care; and 3) Work with other national leaders in community engagement around PD and LBD to develop plans, processes and infrastructure to be ready to engage in multisite clinical trials of palliative care for people with PD in Black/African American and Hispanic populations. This research is Innovative as it represents the first applications of CBPAR to move towards improving the reach of neurology research. This research is Significant as it stands to improve person and family-centered care for a leading neurodegenerative illness, will lead to more scalable interventions, and will advance methods applicable to other neurologic illness.

NIH Research Projects · FY 2026 · 2025-03

PROJECT SUMMARY Retinal degeneration results in low vision and blindness by causing primary death of rods and cones and secondary pathophysiological remodeling of inner retinal neurons. During remodeling, the retinal ganglion cells (RGCs) -the only information output channel of the retina- become intrinsically hyperactive, decreasing the signal-to-noise (SNR) ratio of remaining light responses (mid-degeneration), and of vision restoration methodologies such as optogenetics (after degeneration). Together with layer-specific changes in gene expression throughout the inner retina and reorganization of synaptic connections, remodeling is predicted to dramatically affect the receptive fields and, therefore, corrupt the retinal circuits that are responsible for at least 40 known signal computations of visual information. However, elucidation of the mechanisms behind genetic, morphological, and physiologically-driven circuit corruption is almost impossible without first identifying and manipulating the root cause behind RGC remodeling. We have shown that upregulation and hyperactivation of the retinoic acid receptor (RAR) is necessary and sufficient for degeneration-dependent spontaneous hyperactivity. Inhibition of RAR -without rescuing the death of photoreceptors- results in decreased hyperactivity, decompressed SNR, and improved contrast sensitivity and visual acuity in vivo. This not only highlights the medical significance of this discovery, but also demonstrates that inner retinal computations are essential for proper image-forming visual functionality. In this proposal, we seek to leverage this fundamental breakthrough and our own expertise in the field to dissect the genetic, morphological and physiological events that lead from RAR activation to neuronal remodeling, with the goal of mapping out the extent of circuit corruption in distinct RGC populations, and to understand how these changes in the retina affect key postsynaptic target areas of the downstream visual pathway. Preliminary data show that RAR’s downstream target in Off-RGCs, the purinergic 2x isoform 7 receptor (P2X7), known to cause membrane hyperpermeability in a RAR-dependent manner, is also necessary and sufficient to cause spontaneous and intrinsic neuronal hyperactivity. However, the mechanisms that mediate between RAR upregulation and downstream activation of P2X7, and the interaction between them and neuronal hyperexcitability, are unknown. We propose to study the consequences of degeneration-dependent upregulation of the RAR-P2X7 signaling pathway in RGCs by employing advanced methodologies and innovative technologies, pioneered by our lab and our collaborators. Our expected results will aim to define crucial components in current and future strategies for visual improvement and vision restoration in patients with photoreceptor dystrophies, such as preventing or reversing retinal remodeling concomitantly with treatments aimed at slowing down the progression of degeneration or restoring light responses. Beyond vision impairment, our results will tackle essential questions regarding the mechanisms responsible for the extent and limitations of neuronal plasticity in sensory systems.

NIH Research Projects · FY 2026 · 2025-02

Microbiomes regulate neutrophil responses in sepsis. Sepsis is defined as a systemic inflammatory response to infection that causes vital organ dysfunction. Although sepsis is one of the most common causes of hospital death, patient responses to this disease are highly heterogeneous, making it difficult to identify the critical pathophysiologic processes that lead to sepsis mortality. The normal human microbiota, which plays a fundamental role in the induction and training of the host immune system, is known for its highly heterogeneous composition across different individuals in homeostasis. Growing evidence suggests that the diverse homeostatic microbiome factors are responsible for the heterogeneous host responses to infection and inflammation. The main question to be addressed in this proposal is whether microbiomes in healthy blood differentially prime the immune system, thus differentially predisposing patients to sepsis. Here, we present unpublished preliminary evidence from our laboratory suggesting that (1) in healthy human blood, neutrophils are differentially “trained” (or “primed”) by the microbiome, leading to altered responses to inflammatory stimulation; (2) unlike in human, neutrophils isolated from mice kept in specific-pathogen-free (SPF) facilities (“clean” mice), do not show the microbiome-mediated priming; (3) however, mice that carry wild mouse microbiomes ("dirty" mice) successfully recapitulate the microbiome-mediated training of neutrophils; and (4) furthermore, adoptive transfer of neutrophils from "dirty" mice significantly improves septic survivals in “clean” mice. Migration of neutrophils to sites of tissue infection is vital for pathogen clearance and, thus, host survival. However, neutrophils become hyperactive during sepsis, and they mediate much of the morbidity and mortality associated with the disease. Our overarching hypothesis in this proposal is that the microbiome-mediated priming of neutrophils during homeostasis influences the exaggerated inflammatory response during sepsis. Aim 1 investigate the mechanism underlying the microbiome-mediated immune priming of human neutrophils. will Aim 2 will determine the effects of the microbiome-mediated priming on sepsis mortality using “dirty” mouse models. This proposal addresses mechanisms regarding how the dysregulated host response threatens patient survival and offers a molecular target for dampening the destructive arms of the hyperinflammatory response while promoting disease resolution and tissue recovery.

NSF Awards · FY 2025 · 2025-02

Microbial communities hold transformative potential for bioproduction, environmental cleanup, and human health. However, controlling the balance of bacterial species within these communities to ensure they function effectively remains a major challenge. This project seeks to overcome these barriers by uncovering principles that enable microbial populations to self-regulate and remain stable, inspired by how bacteria naturally exchange genetic information. Using modeling and experiments, these principles will be applied to develop and demonstrate a practical approach for controlling microbial communities. The results will have broad implications for agriculture, healthcare, and environmental science, providing tools to manipulate microbiomes in ways that are reliable and predictable. Beyond the research, this project emphasizes education and accessibility by creating hands-on learning kits that help students visualize and understand complex biological systems. These kits will be used in classrooms and made freely available to teachers and students, opening the door to exciting opportunities in STEM for learners of all backgrounds. By combining cutting-edge science with inclusive education, this work aims to address critical challenges and inspire the next generation of innovators. Engineering stable, precisely controlled microbial populations remains a fundamental challenge in synthetic biology. This project addresses these challenges by developing an innovative platform that leverages horizontal gene transfer (HGT) to self-regulate and stabilize microbial consortia. Specifically, this project will use plasmid conjugation to dynamically balance growth rates and community composition, creating programmable microbial populations capable of maintaining stability across diverse conditions. Four core objectives will be integrated to achieve stability in this way. First, rigorous computational modeling will identify the key parameters governing HGT dynamics and their impact on microbial stability. Second, synthetic engineering methods will be leveraged to design and test modular plasmids with optimized transfer and maintenance characteristics to experimentally validate these models. Third, the platform will be evaluated in real-world scenarios by applying it to microbial-enabled production of curcumin, a valuable natural product. Finally, the project will emphasize education and accessibility by creating hands-on biomodeling kits that combine physical components and software simulations to teach core systems biology concepts. 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 2026 · 2025-01

PROJECT SUMMARY Understanding speech in real-world conditions is a complex process that requires the brain to integrate information about the incoming speech stream concurrently on multiple timescales, ranging from milliseconds to seconds. While previous work has characterized integration timescales across the auditory cortex, it remains unclear the extent to which these temporal integration windows are fixed or whether they vary depending on stimulus processing demands, such as the presence of background noise. Prior studies that have examined this question have been limited to measuring integration windows using linear modeling (e.g., spectrotemporal receptive fields), and much of the relevant research has either been conducted in animals or used coarse neuroimaging measures. As a consequence, much remains unknown about the human auditory cortex integrates information in speech during challenging listening conditions, which is thought to depend upon highly nonlinear computations. In this project, we examine the degree to which auditory cortical integration windows vary depending on the presence or absence of background noise using a novel method (the “temporal context invariance” or TCI paradigm) applied to both scalp EEG (Aim 1) and intracranial EEG recordings (Aim 2). The TCI paradigm makes it possible to measure integration windows from any sensory response, even if that response is a highly nonlinear function of its input. Scalp EEG recordings will allow me to test if there is any overall change in the integration window of auditory cortical responses in the presence of noise, while the unparalleled spatiotemporal resolution of intracranial recordings will enable me to examine the neuroanatomical basis of integration window flexibility. The proposed research will answer longstanding questions about the nature of temporal integration in the auditory cortex, and further our understanding of how the brain reckons with the extreme variability inherent in real-world communication settings in order to arrive at stable representations of speech despite interference from background sounds. This research is a critical first step in understanding the speech perception deficits in noise that are present in auditory neurodevelopmental and attentional disorders, many of which are hypothesized to also involve impairments in temporal processing. In the process of conducting this research, I will develop expertise in several valuable domains: (1) scalp EEG experiments, (2) intracranial EEG experiments, (3) the analysis of high-dimensional time-series data, (4) hypothesis-driven encoding models of speech. These skills complement my prior expertise in fMRI, music, and data-driven component modeling, thus equipping me with a unique and valuable set of experimental and computational skills that will facilitate my transition to an independent research career.

NIH Research Projects · FY 2026 · 2025-01

Abstract Abdominal adhesions are the leading cause of small bowel obstructions, and result when scar tissue forms between the abdominal wall and visceral organs, such as the small intestine, in response to peritoneal tissue trauma during abdominal and pelvic surgery. Adhesion formation occurs in greater than 50% of cases, with the incidence rising to >95% in patients undergoing multiple surgeries. In addition to small bowel obstructions, adhesions can also lead to infertility and chronic pain, and can complicate subsequent surgeries. Collectively, health care costs associated with abdominal adhesion-related complications exceed $5 billion annually in the United States. Currently, standard treatment options for abdominal adhesions are limited to laparoscopic or open surgical lysis. Thus, there is a substantial need to identify therapies to both prevent initial adhesion formation and to ameliorate adhesion persistence and recurrence. However, the mechanisms that drive post- operative adhesion formation are only partially defined, leading to a paucity of translationally relevant therapies. Our exciting preliminary demonstrate that genetic knockdown of the small calcium binding protein, S100a4 results in significant attenuation of adhesion formation. Therefore, in Aim 1 we will leverage this anti- fibrotic mouse model to comprehensively define the temporal molecular programs underpinning adhesion formation and resistance to adhesions. Our preliminary data demonstrates that S100a4 is expressed by both macrophages and fibroblasts/myofibroblasts during adhesion pathogenesis, while S100a4 can function through direct cell-intrinsic functions or as a secreted signaling molecule. Therefore, in Aim 2, we will delineate cell-type specific requirements for S100a4 in adhesion formation and subsequent small bowel obstruction using conditional knockout models and establish the mechanistic functions of S100a4 using pharmacological inhibition and neutralizing antibody approaches. Finally, our preliminary data suggest that delayed, short-term treatment with an S100a4 inhibitor is sufficient to ameliorate mature adhesions. Therefore, in Aim 3, we will leverage this approach to define the mechanisms of adhesion resolution and determine whether short-term S100a4 is sufficient to prevent adhesion recurrence. Collectively, these studies will provide critical insights into the fundamental mechanisms of adhesion formation and amelioration, define the mechanisms through which S100a4 drives adhesion formation, and establish the translational potential of S100a4 inhibition as means to prevent or resolve post-operative abdominal adhesions and adhesion-related small bowel obstructions.

NIH Research Projects · FY 2026 · 2025-01

Therapeutic advances have allowed more adults aged ≥60 years with acute myeloid leukemia (AML) to receive life-prolonging treatments. Nevertheless, the disease remains generally incurable with a two-year overall survival of <20%. In contrast to other cancers, the onset of AML is often sudden, high-risk treatment decisions must be made quickly, and survival is often compromised due to aging-related conditions (e.g., functional impairments). In addition, we and others have demonstrated that up to 78% of older adults with AML and their caregivers experience significant psychological distress. Distress is associated with poor quality of life, increased healthcare utilization, and increased mortality. Shared decision making (SDM) can reduce patient and caregiver distress and is essential to achieve goal-concordant care. Therefore, interventions to improve distress and optimize SDM in older adults with AML and their caregivers are needed. Critical elements of SDM include recognizing that a decision is needed, understanding options, and incorporating patient values into the decision. To achieve SDM, patients must be knowledgeable about their disease, treatment options, and prognosis, and their values must be incorporated into treatment decisions. In partnership with our patient and caregiver advisory board, we have tested the feasibility of a multilevel decisional intervention (UR-GOAL) that addresses critical elements of SDM for older adults with AML. UR-GOAL targets patients (caregivers) and oncologists: 1) Patients view an educational video about AML diagnosis, treatment, and prognosis; complete the BWS value clarification process; and review a summary report of their values with tailored question prompts and resources; 2) Caregivers (if available) view the same educational video and receive the same summary report as patients; 3) Oncologists review a summary report of the patient’s aging-related conditions, perception of prognosis, and values. Patients (caregivers) and oncologists then meet to discuss aging-related conditions, prognosis, and patient values during treatment decision making clinical visits. In our pilot studies, we demonstrated that it was feasible to recruit this population. Preliminary findings showed that compared to those receiving usual care, patient and caregiver randomized to UR-GOAL experienced lower distress at 1 month after a treatment decision was reached. We propose a multicenter randomized controlled trial to evaluate the efficacy of UR-GOAL compared to an attention control for improving outcomes. We will recruit 300 older adults with newly diagnosed AML, their caregivers if available, and oncologists from four institutions. We aim to assess the efficacy of UR-GOAL versus an attention control for: 1) reducing patient distress; and 2) improving objective SDM, patient-perceived SDM, and decisional conflict. We will also assess other patient (perception of prognosis, goal-concordant care), caregiver (distress, perception of prognosis), and healthcare (emergency department visits and hospitalization in the last 30 days of life) outcomes. If successful, the intervention has the potential to be extended to other cancer populations and diseases.

NSF Awards · FY 2025 · 2025-01

The Eocene (56-33.9 Ma) was a time of profound climatic variability as Earth transitioned from the hothouse, ice-free conditions of the early Eocene, to the warmhouse of the middle Eocene, to the coolhouse of the Oligocene, characterized by lower temperatures and the development of permanent ice sheets on Antarctica. Based on these large changes in Earth’s climate, it is reasonable to assume that the composition of the pelagic calcifier ecosystem in the Eocene changed in response to evolving patterns of ocean circulation, continental weathering, and cooling temperature, but there are few Eocene data available to test this assumption. The proposed research will reconstruct changes of the South Atlantic subtropical gyre ecosystem from the early Eocene to the early Oligocene, and it will determine how these changes impacted carbonate production at the surface and its preservation at the seafloor. Data will be generated using sediment cores collected below the oligotrophic waters of the South Atlantic subtropical gyre during the International Ocean Discovery Program Expeditions 390C and 393 (Sites U1557 and U1558). These data will improve the societal understanding of the evolution of the carbon cycle under different climatic regimes. This research will also generate the first complete Eocene record of pelagic carbonate communities and carbonate accumulation rates for the western South Atlantic Ocean, which remains a poorly studied region during a key interval of the Cenozoic. Broader impact activities include the support for two early career researchers, and an outreach program that will promote the participation of high school students from disadvantaged backgrounds in summer research experiences. Additionally, several undergraduate and graduate students will be involved in research activities. On geological time scales, the biologically-mediated production of calcium carbonate at the ocean surface and the burial of this calcium carbonate at the seafloor influence the marine chemistry and, indirectly, the CO2 concentration in the atmosphere. Thus, these processes are important components of the carbon cycle. However, their evolution through time is not well constrained, in particular with oligotrophic systems, which are less productive but cover vastly more area than upwelling regions. The goal of this project is to study how oligotrophic pelagic calcifier communities evolved during a time characterized by different temperatures and CO2 concentrations in the atmosphere (i.e., Eocene) and how these changes have affected carbonate burial at the seafloor. Specifically, the investigators will test the following hypotheses: 1) Surface carbonate productivity changed from the early Eocene to the early Oligocene (~56-32 Ma); 2) These changes were connected to changes in the composition of the pelagic calcifier ecosystem; 3) Changes in the pelagic calcifier ecosystems were driven by changes in surface currents; 4) Above the carbonate compensation depth, carbonate burial was not impacted by deep-ocean circulation. The investigators will evaluate project hypotheses by generating and interpreting mass accumulation rates of planktic foraminifera and calcareous nannoplankton (the main producers of carbonate found in deep sediments), planktic foraminiferal assemblages and percent fragmentation, and benthic foraminiferal accumulation rate from two new International Ocean Discovery Program sites drilled in the western south Atlantic, Sites U1557 and U1558. 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 2026 · 2025-01

Project Summary/Abstract Dr. James Gugger is an Assistant Professor of Neurology at the University of Pennsylvania with clinical expertise in both epilepsy and traumatic brain injury (TBI). His long-term goal as a physician-scientist is to use quantitative neuroimaging to define neurobiologically grounded phenotypes of neurological disorders, which will improve our understanding of disorders such as epilepsy and TBI and ultimately improve care. The neurobiological phenotype of TBI involves both focal and diffuse injury mechanisms. Both animal and human data implicate damage to the limbic network in those with epilepsy after head injury. This proposal tests the hypothesis that the effects of focal and diffuse injury mechanisms on the limbic network can be used to distinguish patients with TBI who will develop epilepsy from those who do not. Experiments will utilize neuroimaging data from a large, well-phenotyped cohort of participants with TBI and uninjured controls. The specific aims are (1) to define the relationship between focal post-traumatic lesions and brain networks implicated in post-traumatic epilepsy (PTE) and (2) to determine the profile of diffuse injury in brain networks implicated in PTE. This project will uncover neuroimaging phenotypes present prior to the onset of PTE and advance us towards identification of biomarkers for epilepsy risk stratification. The proposal builds on Dr. Gugger’s prior research on quantitative multimodal neuroimaging in TBI and epilepsy. With the support of a team of mentors at the University of Pennsylvania who are leaders in the field, he will gain expertise in functional neuroimaging, statistical modeling of multimodal neuroimaging data, and the conduct of prospective neuroimaging studies. Dr. Gugger’s team of mentors at the University of Pennsylvania (Drs. Diaz-Arrastia, Davis, Shinohara, and Detre) have strong track records of mentorship and will provide specific expertise in his areas of skill development. He will also leverage his existing relationships with large multicenter consortia focused on PTE research (Transforming Research and Clinical Knowledge in TBI [TRACK-TBI] Network, Military Injuries—Understanding PTE: Bioinformatics with big data to examine multi- modal PTE biomarkers [MINUTE], and the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy [EpiBioS4Rx]) to launch future studies as an independent physician scientist. Dr. Gugger’s clinical background in epilepsy and TBI, with the additional support of this career development award and his unique mentorship opportunities, will position him to succeed as an independent physician-scientist focused on using quantitative neuroimaging to improve the lives of people with epilepsy and TBI.

NIH Research Projects · FY 2026 · 2024-12

Modified Project Summary/Abstract Section Physician-scientists bring a unique perspective to biomedical research, informing clinically inspired basic science questions (bedside-to-bench), translating fundamental research back to the clinic (bench-to-bedside), and guiding implementation science on behalf of public health (translation to the community). On the other hand, there are numerous challenges contributing to the declining number of physician-scientists, including individual (financial debt, length of time for training, balance of clinical productivity and protected time for increasingly competitive funding), institutional, and national factors. Robust research programs during residency can catalyze the development of physician-scientists poised to ask fundamental questions informed by clinical insights which will be crucial for advancing discovery in NIAID mission-critical immune mediated diseases in the coming decades. The University of Rochester (UR) has a long history of support for trainees along the physician-scientist continuum, with a medical scientist training program in its 50th year, Physician Scientist Training Program (PSTP) in Internal Medicine (IM), and well-established research tracks in the participating residency programs (Medicine, Pediatric, Med-Peds, and Dermatology). The primary goal of this multidisciplinary ROChester Stimulating Access to Research during Residency (ROC StARR) Health and Immune Function Across the Lifespan R38 is to train the next-generation of physician-scientists to lead the development, implementation, and evaluation of new clinical modalities to diagnose, treat and prevent autoimmune, allergic, inflammatory, and infectious diseases across the age spectrum from infants to older children to adults to the aging population via the following Aims: 1) recruit an exceptional, talented pool of Medicine, Pediatric, and Dermatology Residents and provide them with high quality, rigorous training in 3 defined pillars of translational, clinical, and health outcomes research through comprehensive didactics and team science initiatives, 2) provide 1-2 years of mentored research with the support of a multidisciplinary physician-scientist focused mentorship team uniquely suited to instill in our trainees the in-depth knowledge and skills needed to conduct cutting-edge research in autoimmune, allergic, and infectious diseases with high clinical impact, 3) develop individualized career development plans and an infrastructure to foster the physician-scientist trajectory from resident to fellow to faculty with the goal of expanding the number and breadth of medical resident education opportunities for residents performing research in immune-mediated diseases, and 4) perform robust evaluation and tracking to demonstrate the impact of the StARR. ROC StARR will be led by PDs Jennifer Anolik, MD, PhD (Medicine) and Kirsi Järvinen-Seppo, MD, PhD (Pediatrics) who have a longstanding history of clinical, education and research collaboration and have strategically assembled a team of 35 multi-disciplinary physician-scientist faculty preceptors to support two to four Resident-Investigators each year with thematic emphasis on immune responses during development, aging, and disease.

NIH Research Projects · FY 2026 · 2024-12

PROJECT SUMMARY The objective of this proposal is to characterize a regulatory signaling axis which promotes astrocyte-driven CNS pathology in Parkinson’s Disease (PD) and to provide the necessary training for me to become a successful physician-scientist. PD is characterized by progressive motor deficits, neurodegeneration, and neuroinflammation. α-synuclein (αSyn) aggregates into fibrils in PD and injection of pre-formed αSyn fibrils (PFFs) into the mouse striatum recapitulates hallmarks of PD pathology. Astrocytes regulate central nervous system (CNS) inflammation in neurologic diseases including PD and Multiple Sclerosis (MS) via interactions with other cells including microglia. PD-associated stimuli such as αSyn further trigger astrocyte pro-inflammatory functions. Critically, blockade of astrocyte inflammatory activities in PD and MS models ameliorates disease. However, the pathways that modulate astrocyte activity in PD are poorly characterized. Thus, a deeper mechanistic understanding of these regulatory pathways is likely to identify mechanisms of disease pathogenesis and potential therapeutic targets for PD. The Quintana lab previously showed that the sigma-1 receptor (SigmaR1) boosts astrocyte pro-inflammatory responses through the activation of the IRE-1α-XBP1 signaling in a MS mouse model. Furthermore, astrocyte- specific SigmaR1 knockout reduces astrocyte and microglia pro-inflammatory responses, suggesting that that SigmaR1 signaling in astrocytes boosts microglial pro-inflammatory functions. I have shown in vitro that astrocytes treated with αSyn PFFs and cytokines display upregulation of XBP1 and the pro-inflammatory molecule IL-1β. In vivo, I have shown that SigmaR1 inactivation prevent the development of motor deficits in response to PFF injection. Thus, my data suggests that αSyn incites XBP1 and pro-inflammatory signaling and SigmaR1 inhibition can prevent hallmarks associated with PD. In this proposal, I will test the hypothesis that SigmaR1 inhibition will limit astrocyte pro-inflammatory functions and CNS pathology in PD. In Specific Aim 1, I will evaluate the role of SigmaR1 on astrocyte and astrocyte-microglia pro-inflammatory responses induced by PFFs and cytokines. In Specific Aim 2, I will evaluate the effect of genetic and pharmacologic SigmaR1 blockade on CNS pathology and inflammation in the pre-clinical mouse model of PD induced by injection of PFFs. Completion of these aims will characterize astrocyte responses to αSyn, their interactions with microglia, and the regulation of their disease promoting activities in PD. Furthermore, this proposal will integrate the clinical and research training necessary for me to become an independent physician-scientist.

NIH Research Projects · FY 2026 · 2024-12

NEUROCITY is an innovative and transformational program hosted by the University of Rochester (UR) that is focused on training promising undergraduate students from The City University of New York (CUNY) is one of the largest public university systems in the United States, comprising multiple institutions with strong undergraduate enrollment that are often under-resourced with respect to access to research-intensive training environments. The overarching goal of NEUROCITY is to develop well-rounded and technically-skilled undergraduate researchers who are highly competitive for top-rated neuroscience PhD programs. NEUROCITY emerged in 2021 from a partnership between faculty at UR and the City College of New York (CCNY), one of the 25 colleges that comprise the CUNY system. In NEUROCITY, scholars engage in a hands-on research training program in established laboratories at UR during the summer, and participate in a series of career and professional development seminars and workshops that prepare students for navigating the many challenges and barriers that are faced in graduate school. NEUROCITY has helped CCNY students make major leaps into higher-end education, such as admissions to Ph.D. programs at R1 institutions. In this proposal, we expand the NEUROCITY experience to provide more continuous research, mentoring, and career development opportunities to all undergraduate students from the CUNY system. We build on the success of NEUROCITY through three foundational aims: (1) Provide an immersive research and mentoring experience. NEUROCITY Scholars actively participate in a series of research activities at UR that provides them with critical research and analytical skills crucial for graduate school. (2) Provide a rigorous career development program. NEUROCITY scholars participate in numerous seminars, workshops, and networking events that are critical for their career and professional development. In particular, scholars will have the opportunity to attend the Society for Neuroscience (SfN) annual meeting, and present their work at the Early Career Poster Session of SfN. (3) Provide a continuous research and mentoring support network. NEUROCITY is unique in that it provides research and mentoring opportunities beyond the summer, delivering a more sustained experience that sharpens critical thinking and research skills, and leading to highly trained scholars who are more competitive for graduate school. Through these continued research, mentoring, and career development experiences, our scholars emerge as empowered and skilled professionals ready to make meaningful contributions to the field of neuroscience at the graduate level. Importantly, NEUROCITY employs a holistic selection approach to recruit students that have an excellent track record in the classroom and at the bench, as well as those students who show promise in neuroscience research, but have not had the opportunity to engage in research due to barriers in their personal lives (e.g., working after school to help support their households). As such, our selection expands the pool of well-prepared trainees entering neuroscience PhD programs which ultimately strengthens the biomedical research workforce.

NSF Awards · FY 2024 · 2024-12

This award will partially fund attendance for eight (8) students attending the doctoral consortium for the 2024 IEEE International Symposium on Mixed and Augmented Reality (ISMAR). ISMAR is a well-known venue for research on the underlying technologies for virtual, mixed, and augmented reality. ISMAR also includes research on effective methods for interaction with, in, and through these systems and on applications of these technologies to socially important areas, including education, training, communication, and entertainment. The doctoral consortium will allow student attendees to present their research interests, plans, and results to a panel of researchers in related fields and receive specific and constructive feedback. At the conference's poster session, students will get in-depth feedback through one-on-one meetings with their mentors, and broader perspectives from expert and student peers from a wide variety of disciplinary, topical, and institutional backgrounds. The agenda of the doctoral consortium was designed specifically to help student participants to "think big" and develop the strategic insight and long-range vision that will help guide them toward continued important contributions to science and engineering research beyond graduate school. Beyond its impact on the research itself, the doctoral consortium will have a broader impact on both student attendees and the research community. Through interactions at the doctoral consortium and the conference itself, students will be able to develop their professional networks in the ISMAR research community as well as their awareness of and ability to navigate future career paths. Students are selected based on the quality of their applications, financial need and first time attendee status, and their ability to contribute a breadth of perspectives to the doctoral consortium that will enhance the experience for other students. 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 2026 · 2024-11

Despite the availability of antiviral drugs and vaccines, the influenza virus causes widespread infection, leading to more than 35,000 deaths in the United States annually . After influenza infection, tissue -resident CD8+ memory T cells (TRMs) are generated in the respiratory tract and rapidly reactivated upon reinfection, providing immediate effector functions to limit viral replication and immunopathology. Therefore, the generation and maintenance of robust long-term memory CD8 T cells in the respiratory tract is an important strategy for effective vaccine design. Indeed, several intranasal influenza vaccines were developed to mimic a natural infection, which brings the advantage of eliciting tissue resident immunity to prevent or eliminate infection at the site of entry. However, unlike in the skin or intestine, TRM cells in the respiratory tract are relatively short-lived with increased apoptotic signatures. Thus, immunization of the respiratory tract with mucosal vaccination often results in inadequate protection. We undertook this study to address a key question regarding the nature of the tissue microenvironment that aids TRM establishment in the respiratory tract. Importantly, can we harness these tissue- specific cues to prolong TRM longevity at the tissue sites? In our unpublished preliminary studies, we tracked the fate of diverse myeloid cells in the lung after influenza infection and discovered that a subset of the newly recruited monocytes differentiates and persists in the mouse lung for more than 4 months after infection. Surprisingly, selective depletion of the novel monocyte subset significantly reduced TRM formation. This long- lasting monocyte subset produces a high level of galectin-1 (Gal-1), which directly activates CD2 expressed on CD8 T cells and enhances TRM-mediated sensing of TGF-β, a key cytokine that promotes virus-specific memory T cell differentiation and tissue persistence. Based on these findings, we propose the presence of a “monocyte- derived memory-like subset” that may prompt functional adaptations during influenza infections. We further hypothesize that the Gal-1/CD2/TGF-β axis is a major cell-intrinsic program through which tissue-resident myeloid cells guide long-lasting T cell memory formation in the respiratory tract. If the innate immune-mediated antiviral memory response persists at the site of antigen exposure, greater protection against viral infection may be achieved, thus offering a promising strategy for effective vaccine development. Indeed, we also showed that intranasal administration of recombinant Gal-1 as an adjuvant for a live-attenuated influenza vaccine induced superior TRM responses. We will (1) investigate monocyte differentiation during immune memory formation after influenza infection, (2) determine how Gal-1 produced by the novel monocyte subset regulates protective antiviral T cell immunity, and (3) test a novel nasal vaccine strategy using recombinant Gal-1. The results of these studies will provide a useful scientific basis for the design of vaccine strategies capable of establishing productive crosstalk between innate and adaptive immunity, leading to the induction of durable immunity, and may have a tangible impact on vaccine strategies against other respiratory viruses.