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2024 Seed Award winners with Provost, Francis Doyle, and Vice President for Research, Jill Pipher, at the Celebration of Research. Photo by Deirdre Confar. 

Research Seed Funding awards are competitively awarded and help faculty more successfully advance competitive research proposals by supporting the generation of preliminary data, pursuing new directions or collaborations in research, and other endeavors. Investigators may propose projects in one of two categories. Category 1 - single PI projects of any type with budgets up to $50,000 for one year; Category 2 - multi-PI projects supporting a new collaboration between two or more disciplines with budgets up to $100,000 for one year.

Social Sciences

Fostering Student Persistence and Degree Attainment: An Evaluation of the Massachusetts Community College SUCCESS Initiative
Despite high enrollment rates in community colleges, persistence and completion rates have lagged due to students’ academic unpreparedness, challenges navigating academic paths and campus life, limited resources, and the need to combine studying with work and other responsibilities. Higher education research underscores the potential of wraparound student support programs to significantly improve persistence and graduation rates. The Accelerated Study in Associate Programs (ASAP) at community colleges of the City University of New York (CUNY) is a successful model that demonstrated doubling of graduation rates in randomized trials. However, despite the adoption of ASAP-inspired programs in many colleges, there’s a noticeable absence of research-informed guidance for effective implementation. To address this gap, we propose a qualitative study focusing on the implementation of the “Supporting Urgent Community College Equity through Student Services” (SUCCESS) initiative, introduced by the Massachusetts legislature in 2021. SUCCESS allocates funds to the state’s 15 community colleges to provide evidence-based wraparound services aimed at enhancing student persistence and degree completion. This qualitative study aims to contribute to the growing body of literature guiding the translation of research evidence into practice in higher education by examining how community colleges implement SUCCESS. This initial work will be a precursor to a more extensive study on the impact of SUCCESS on student persistence and degree attainment at Massachusetts community colleges, with plans to seek multi-year external funding for a comprehensive impact study. This project positions Brown at the forefront of educational research and state policy focused on college persistence and graduation.
PI: Lindsay Page, Annenberg Associate Professor of Education Policy
Key Personnel: Aizat Nurshatayeva, Senior Research Associate, Annenberg Institute for School Reform 

Physical Sciences 

Data-driven stabilization of close-proximity quadrotor flight
Quadrotor flying vehicles ("drones") are finding widespread use in many applications including search and rescue, remote monitoring, inspection in agricultural and industrial settings, and operations in hazardous or even extra-terrestrial environments.  One critical weakness in this exciting new arena is the inability to operate dense swarms of quadrotors due to aerodynamic interference of the rotor wakes.  This weakness also prevents many new and advanced applications such as synthetic aperture imaging or cooperative assembly tasks.  The goal of this project is to acquire data on multi-quadrotor interactions - force,  torque and velocity interactions - over a wide range of operating conditions and spatial separation,  and to use data-driven analysis techniques to develop efficient, accurate and practical flight controllers to compensate for the close-proximity interference. Despite the importance of this problem to advanced flight robotics, there has been little work presented in this area. The collaboration between the professors Breuer and Ayanian - who bring expertise from the aerodynamic and computer science fields - presents an opportunity to put Brown at the forefront of high density cooperative drone flight control.  The results from this effort will provide significant first steps necessary for the PIs to apply for longer-term, more substantial funding from government agencies (NSF, DARPA, NASA, etc) and private industry.  Intellectual property related to the aerodynamic design and control of drone swarms, as well as trajectory planning for complex swarm maneuvers is anticipated.
PI: Kenneth Breuer, Professor of Engineering
Co-PI: Nora Ayanian, Associate Professor of Computer Science and Engineering

Data-driven design of a low power, nanoscale neural network using non-linear spin-wave interference
Semiconductor technologies are rapidly facing challenges in scalability, energy consumption, and reduced latency. These challenges are driving a significant effort to develop alternatives to CMOS-based technologies to meet the demands of future computing technologies. Neuromorphic computing could address these challenges with high performance and low-power artificial neural networks. These technologies can provide increased computing performance with enhanced features and reduced cost but rely on traditional chip technologies not designed for their operation. This collaboration seeks to develop a first of its kind spin wave neural network comprised of two-dimensional magnon scattering centers, also known as magnonic crystals. We hypothesize that by using inverse design machine learning processes and high throughput micromagnetic simulations, we will optimize the array of spin wave scattering sites to create a neural network capable of number classification based on spin wave interference patterns. In this collaborative proposal, our interdisciplinary team will test our hypothesis and address design challenges associated with the vast optimization parameter space by developing a coherent computation, materials synthesis and characterization, and spin wave imaging platform. This platform will enable a learning loop, where the prediction and discovery of unique magnonic crystal topologies will be reinforced by feedback from micromagnetic simulations and experimental verification via novel quantum imaging platforms. The outcomes of this project include a framework and design protocol by which to optimize spin wave scattering platforms for advanced computing, new fundamental insight on spin wave-spin wave interactions, and the experimental realization of a low power spin wave neural network.
PI: Lucas Caretta, Assistant Professor of Engineering
Co-PI: Miguel Bessa, Associate Professor of Engineering

Brown Center for Digital Identity and Privacy
How does identity/identification/authentication work online? Currently, corporations collect everyone's information and act as identity verification providers. Not only is this a disaster from the privacy point of view, but it also gives these corporations the power to mess up our identities online, to cause us to be denied important services, and to report incorrect information about us to other entities. How should it work online? A better approach is one where each individual has everything they need to prove their own identity and relevant identity attributes --- or to provide no information about themselves at all other than the fact that they are authorized to participate in an online transaction. This project aims to make this vision a reality. Through my 25-year research career, I have worked extensively on anonymous credentials, which are cryptographic algorithms that enable users to prove that they are authorized and have necessary credentials without revealing any additional information. Now the time has come to put all this into practice.
PI: Anna Lysyanskaya, James A. and Julie N. Brown Professor of Computer Science

Bolstering sea ice models using multi-proxy reconstructions for warmer-than-present periods of the recent geological past
Over the past 45 years, Arctic sea ice has drastically declined at an unprecedented rate that has not been seen in the past 1,500 years of historical records. This alarming trend is exacerbated by the Arctic's rapid atmospheric warming, which is four times faster than the global average. Sea ice loss not only contributes to warming but also has far-reaching ecological, societal, and geopolitical implications. We are thus urgent to accurately and quantitatively project future Arctic sea ice changes based on future climate trajectories. However, current state-of-the-art climate models exhibit significant disparities and large uncertainties, offering little value in formulating solutions for Arctic and global sustainability. Here, our proposal will leverage the unique strengths at Brown University, combining expertise in organic geochemistry, paleoclimatology, and sea ice modeling, to achieve three core objectives: (1) synthesizing robust, quantitative Arctic sea ice reconstructions based on multiple sea ice proxy records for two recent “warmer-than-present” periods (Marine Isotope Stages 5 and 11), which serve as best geological analogues for our future, (2) providing essential proxy-based sea ice data for model calibration, and (3) critically examining the underlying parameterization in sea ice models, to bolster model accuracy in projecting future Arctic sea ice. The research will generate key preliminary data, provide opportunities for career development of early career researchers, and promote outreach initiatives and mentoring undergraduate students, all of which will enhance the competitiveness of our proposal for sustained external fundings.
PI: Yongsong Huang, Professor of Earth, Environmental, and Planetary Sciences
Co-PI: Steven Clemens, Professor of Earth, Environmental, and Planetary Sciences (Research)
Co-PI: Christopher Horvat, Assistant Professor of Earth, Environmental and Planetary Sciences (Research)

Broadening the Horizons of Pico Second Silicon Devices to Space-Based Operations
Position-sensitive silicon devices with internal gain, such as Low Gain Avalanche Diodes (LGADs), are capable of tens of pico-second timing resolution. Similarly, Resistive Silicon Devices, such as AC-coupled Low Gain Avalanche Diodes, achieve a fine spatial resolution while maintaining the LGAD's timing resolution with near to 100%fill factor, achieving time and space (4D) tracking measurements for collider-based experiments. Because of their low power consumption and tolerance to high radiation, they are also ideal candidates for satellite spectroscopy. However, the performance of this new technology is strongly affected by environmental factors such as temperature, humidity, and mechanical stresses. The lack of universal models that account for the path of charge carriers in the multiplication layers hinders their application to new horizons. As their performance has never been studied to account for environmental stresses, the entire operational envelope of these devices remains unmapped. This project will establish a performance-to-conditions map by characterizing the devices' performance dependence as a function of the fabrication properties and the environmental operating conditions. By accounting for this performance change, the device's output signal can be corrected for the environmental factors using Artificial Intelligence and Machine Learning techniques, thus harnessing an optimal readout performance outside the typical operating conditions. The acquired knowledge for the university will allow for a sensor fabrication that can be tuned explicitly for space applications.  Due to reducing the amount of support material brought to space, the university will produce competitive alternatives to currently planned technologies for space-based spectroscopy. 
PI: Gaetano Barone, Assistant Professor of Physics (Research)

Emergent mechanical behavior of charged hetero-interfaces in solar cells
Interfaces between dissimilar materials (semiconductors, dielectrics, metals) are ubiquitous in multi-layered energy-conversion and -storage devices, such as solar cells and batteries. The reliability of these devices critically depends on the mechanical adhesion at these interfaces. Since most of these functional devices are ‘dynamic,’ during their operation under external stimuli (electric field, light) many hetero-interfaces typically accumulate charged species (electrons, holes, vacancies, interstitials), thereby generating internal charged layers. Unfortunately, to-date the charged-interface effects have not been considered explicitly in the adhesion and fracture of interfaces in these devices. The proposed research will focus on the burgeoning perovskite solar cells (PSCs) where such effects are expected to be critical for their long-term durability and reliability. The objective is to develop experimental tools for gaining fundamental understanding of the important effects of accumulated charge and external stimuli (electric field, light) on the adhesion and fracture behavior of a range of hetero-interfaces relevant to PSCs. This will address the wide knowledge gap in this important area, and help take materials science of adhesion to the next level, leading to discovery of hitherto unknown electro-photo-mechanical coupled phenomena. The basic tools and understanding developed here can be extended to the study of other energy-related devices (batteries, fuel cells, supercapacitors) for an outsized impact. The results from the proposed seed project will serve as preliminary data for at least two sustainable-energy-related proposals being developed by PI and his colleagues for submission to external agencies.
PI: Nitin Padture, Otis Everett Randall University Professor of Engineering

A novel route for destroying “forever chemicals” 
There is growing concern regarding chemical compounds from the per- and poly-fluoroalkyl substances (PFAS) family of industrially produced materials. They offer many possibilities for human exposure, and there is increasing concern, regarding negative health effects from such exposures. The term “forever chemicals” has been applied to these materials because many in this class of compounds do not break down in the natural environment. Allowable regulatory levels for PFAS in drinking water are now in the parts per trillion range.  Because there is no easy method to break these chemicals down this has led to widespread adoption of carbon adsorption technologies to remove them from water. While this removes the PFAS from drinking water, they remain in the activated carbon, which cannot be dumped in landfills. The PFAS need to be destroyed, which has often involved incineration of the PFAS-containing carbons. Hazardous waste incinerators are unpopular and difficult to operate, and there is a desire to identify alternate destruction technologies. Recent work at Brown has identified the particular chemical species which make incineration effective, and other much older work (from the coal liquefaction field) points to the possibility of designing a completely different PFAS destruction technology. What is proposed is a laboratory demonstration of the new technology. A successful demonstration would allow follow-on proposals to any of a number of agencies all of whom are interested in the problem of PFAS destruction (e.g., EPA, DOD- through its SERDP and ESTCP programs, NSF).
PI: Eric Suuberg, C.V. Starr Professor of Technology Entrepreneurship, Professor of Engineering
Co-PI: Franklin Goldsmith, Associate Professor of Engineering

Designing and controlling quantum optical properties at 1D-2D mixed dimensional interfaces
Advancements in quantum information sciences rely largely on the experimental realization and control of quantum optical properties, such as single-photon emissions and superfluorescence. This necessitates the development of scalable quantum light sources in solid-state materials. While significant progress has been made in engineering these properties within confined excitonic systems, achieving highly tunable homogeneous quantum light in the telecom-wavelength range (1.3-1.6 µm) remains a formidable challenge. The PIs propose a new approach involving mixed-dimensional heterostructures, comprising single-walled carbon nanotubes (SWNTs) on hexagonal boron nitride (hBN) and transition metal dichalcogenides (TMDCs), to realize homogeneous quantum light sources in the telecom-wavelength range. The combination of expertise in SWNT synthesis and high-resolution microscopies in the Kuehne Lab, and the 2D quantum device fabrications and cryogenic spectroscopy/microscopy in the Bai Lab is coherent and will uniquely enable the implementation of this project. Engineering high-quality quantum light sources is a critical task in the ascending field of quantum information science; this collaborative effort will establish the groundwork for designing mixed-dimensional heterostructures for programmable quantum light sources, and will strengthen Brown’s position in quantum optical research. Importantly, the outcomes hold promise for the development of on-chip nanoscale quantum light sources with tunable, high homogeneity in telecom-wavelength emissions, garnering significant interest from various funding programs, including NSF-DMREF, NSF-EFRI, and MRSEC IRG topics.
PI: Yusong Bai,  Assistant Professor of Chemistry
Co-PI: Matthias Kuehne, Assistant Professor of Physics

Life Sciences and Physical Sciences 

Long-circulating vascular treatment for life-threatening bloodstream infections
The goal of this project is to demonstrate feasibility for a long-circulating treatment targeting bacterial toxins that contribute to the debilitating effects of bloodstream infection (BSI). Technologies developed in the participating investigators’ laboratories will be combined as a novel solution to the problem. Dr. Shukla brings expertise in creating nanoparticle formulations that are responsive to bacterial virulence factors, such as hemolysins. Lipid vesicle nanoparticle formulations developed by Dr. Shukla will be combined with a technology developed by Drs. Darling and Mathiowitz, hyper-compliant microparticles (HCMPs), that hold great promise as long-circulating vascular carriers. HCMPs are spherical hydrogel microparticles sized similarly to white blood cells but with an extremely low elastic modulus that allows them to squeeze through small constrictions in the vasculature. The primary goals of the proposed project are to 1) develop a hemolysin-sorbent HCMP using red blood cell (RBC) membrane-derived nanoparticle vesicles for reducing RBC morbidity associated with BSIs and 2) assess HCMP persistence, biodistribution, and ultimate fate in an in vivo model. A combination of in vitro and in vivo experiments will be completed to achieve these goals. The anticipated findings will lay the groundwork for a larger project and external proposal to demonstrate the therapeutic effectiveness of continuously circulating HCMPs that contain hemolysin-sorbent nanoparticles for ameliorating the negative impact of BSI.
PI: Eric M. Darling, Associate Professor of Medical Science, Associate Professor of Engineering, Associate Professor of Orthopaedics
Co-PI: Anita Shukla, Elaine I. Savage Associate Professor of Engineering
Co-PI: Edith Mathiowitz, Professor of Pathology and Laboratory Medicine, Professor of Engineering

Life and Medical Sciences

Calcium channel specific recording and manipulation of neuronal activity
Calcium entry that results from neuronal activity is an essential second messenger implicated in critical processes including synaptic activity and intrinsic neuronal firing; processes that ultimately impact circuit function and behavior. There are only a handful of tools to accurately monitor calcium levels at high spatial resolution, but no tools exist that use activity-driven calcium entry to provide feedback control to downstream elements. Furthermore, current calcium indicators use damaging wavelengths that cause tissue overheating. Here, we propose to expand the capabilities of BioLuminescent OptoGenetics (BL-OG) to measure intracellular calcium levels but also manipulate circuit activity. In this pilot project, we propose to optimize LumiPoreIns (LMPs) where a voltage-gated calcium channel (CaV) is tethered to a calcium-sensitive luciferase. CaVs are naturally targeted to the terminal and open during neuronal activity. This will trigger bioluminescence only when cells are being activated. We expect to use this bioluminescence triggered by calcium to activate optogenetics elements localized on the same cell or postsynaptically to either stimulate or suppress neuronal activity. We predict that these new tools can have multiple applications: a) By measuring the calcium-sensitive bioluminescence, we will be able to precisely image cells and synapses that are activated when neurons are exposed to natural stimuli; and b) our optical design allows for activity-dependent real time feedback at the cell and synapse-specific level. This re-wiring of synapses has the potential to be utilized to treat neurological disorders where there is altered neuronal activity including epilepsy, addiction, and pain. 
PI: Arturo Andrade, Associate Professor of Brain Science (Research), Associate Professor of Neuroscience (Research)

Children understand that what you say depends on how you say it
How children learn language is a major puzzle for cognitive science. A core piece of this puzzle is vocabulary acquisition. How do children connect words, especially nouns, to real-world objects amid many possible referents? In this project we develop a project that explores how children may exploit not just the words, but the way the words are said, to learn what they refer to. Prosody, involving variations in pitch, duration, and loudness, can act as a signal that guides interpretation. For instance, the sentence “I like broccoli” can have different meanings based on whether “I” “like” or “broccoli” bears prosodic emphasis, by indicating which word contrasts with salient alternative meanings. Our initial findings from a study manipulating prosody reveals that children's interpretation of novel nouns depends on such prosodic cues. We plan to further explore this possibility with three main objectives: (1) Investigating infants use of prosody in learning word meanings, (2) examining the ecological validity of prosodic cues in caregiver-child dyads, and (3) conducting a systematic review and prosodic analysis of prior word learning studies. This comprehensive approach seeks to establish the degree to which prosody shapes word learning, potentially deepening our understanding of how children approach language learning.
PI: Roman Feiman,  Thomas J. and Alice M. Tisch Assistant Professor of Cognitive, Linguistic, and Psychological Sciences and Assistant Professor of Linguistics
Co-PI: Gabor Brody, Postdoctoral Research Associate in Cognitive, Linguistic, and Psychological Sciences

From 1 to 100: How learning affects large populations of inferior temporal neurons
Understanding the neural mechanisms responsible for the perceptual and cognitive capacities of higher mammals, especially primates, is essential for better understanding how normal, and abnormal, brains develop and function in the real world.  The aim of this proposal is to begin to understand how large populations of single neurons in the brain adapt to efficiently process objects of the visual world. Our working hypothesis is that in the normal adult brain of both human and non-human primates, cells in higher visual areas remain plastic and modifiable with experience.  Specifically, evidence shows that individual neurons in the inferior temporal lobes (IT) of the monkey have physiological properties that remain modifiable into adulthood. Adult primates can clearly learn to recognize visual objects, but the neural correlates of this have only been indirectly traced back to the activity pattern of single neurons.  Recent advances in recording technologies make it possible to record from hundreds of neurons from target regions, potentially transforming our understanding of how circuits in the brain operate in real time to control behavior.  The goal of this project is to obtain preliminary data using these probes.
PI: David Sheinberg, Professor of Neuroscience

Feasibility of a Rigorous fMRI Design to Study Menstrual Cycle Effects on Psychopathology
Strong individual differences in neural sensitivity to normal hormone changes can drive lability in a wide range of emotional, interpersonal, and behavioral symptoms (hormone sensitivity); however, neural mechanisms underlying these effects are not well understood. Based on evidence across studies of menstrual-related mood disorders, our team has proposed a Dimensional Affective Hormone Sensitivity framework (DASH) in which sensitivity to one or more types of hormone changes produces or exacerbates distinct sets of psychiatric symptoms. The proposed study is a pilot test of an innovative, scientifically rigorous approach to modeling neural underpinnings of DASH with resting state and task-based fMRI. Study design capitalizes on the infrastructure and sample of PI Peters’s ongoing study examining links between specific steroid hormone changes, proposed behavioral mechanisms, and symptom flux. A subsample (N=5) with demonstrated hormone sensitivity and data for personalized estimates of menstrual cycle phases will undergo scans at four time points across a cycle, in counterbalanced order, with urine hormone testing on scan days. Aim 1: Evaluate the feasibility of using 4 resting state scans to develop idiographic models of cyclic hormone shifts and changes in the functional connectivity of default, frontoparietal, reward, and salience networks. Aim 2: Evaluate a task battery for sensitivity to cycle-based within-person differences in neural activation, using paired contrasts to minimize participant burden while testing multiple tasks per proposed mechanism. We will develop a subsequent fully-powered proposal applying these methods to differentiate between specific patterns of menstrual cycle exacerbation and disseminate methods for use in the broader field.
PI: Jessica Peters, Associate Professor of Psychiatry and Human Behavior
Co-PI: Jennifer Barredo, Assistant Professor of Psychiatry and Human Behavior (Research)

Leveraging expert-verified data to bring wildlife parasitology into the genomics age
We are on the cusp of a genomics revolution to usher in an era of precision wildlife parasitology—but achieving it requires reforming long-standing traditions in the field. Biologists and health practitioners need to monitor wildlife to ensure effective conservation and identify emerging infectious diseases that may threaten humans and livestock. But we may often misunderstand host-parasite interactions because we rely on overly simplistic methods to study parasite diversity in nature. Fortunately, emerging molecular and bioinformatic techniques can help overcome traditional limitations. We plan to establish genomic workflows to more precisely characterize the diversity and distribution of gastrointestinal parasites that infect wildlife in tropical hotspots. We will accomplish this by constructing and utilizing one of the largest expert-verified databases of helminth DNA in the world. This database will bridge the gap between today’s ‘gold-standard’ practice of using microscopes to painstakingly identify parasites in the field and tomorrow’s need for ‘field-ready’ methods that provide more cost-effective, accurate, and timely parasite identifications—especially for the practitioners who need these data at the right times and places to take action. We will initially use these emerging tools to map hard-to-identify parasites onto wildlife hosts in tropical forests—sloths, monkeys, and tapirs among others—in ways that are more robust than standard techniques could provide. This exciting venture features interdisciplinary collaboration among veterinarians, parasitologists, molecular biologists, and ecologists. It will provide world-class opportunities for students and researchers at Brown to engage with non-profit organizations that focus on wildlife conservation, health, and human livelihoods.
PI: Tyler Kartzinel, Peggy and Henry D. Sharpe Assistant Professor of Environmental Studies, Assistant Professor of Ecology, Evolution, and Organismal Biology

Mechanisms of JCPyV Invasion of Brain Parenchyma
The human polyomavirus JC (JCPyV) infects 50-80% of people worldwide. Initial exposure typically occurs during childhood and becomes a lifelong, persistent infection of peripheral organs, including the kidney. Under immunosuppression, such as when a patient has AIDS or is treated with immunotherapies for multiple sclerosis or cancer, JCPyV can migrate to the central nervous system (CNS) and cause the often-fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). A critical gap in our understanding of JCPyV pathogenesis is that it is not known how the virus overcomes the barriers that restrict the access of pathogens to the CNS, including the blood-CSF barrier formed by the choroid plexus (BCSFB) and by the endothelial cells of the blood brain barrier (BBB). Recently, we discovered that JCPyV can productively infect choroid plexus epithelial cells, leading us to hypothesize that JCPyV enters the CNS via the BCSFB. Our preliminary data shows that virus infection of choroid plexus epithelial cells triggers the downregulation of tight junction proteins and the upregulation of inflammatory molecules, both of which are associated with barrier disruption and neuroinvasion. In addition, it is unknown if JCPyV can invade the CNS through the BBB, despite clinical evidence that PML lesions often form near the brain vasculature. Here, we propose to analyze how JCPyV disrupts barriers and crosses into the CNS. This work investigating how the virus traffics from the periphery to the brain to cause PML is critical for the discovery and design of therapies to prevent this fatal disease.
PI: Sheila Haley, Assistant Professor of Molecular Biology, Cell Biology and Biochemistry (Research)

Intersection of chromatin regulatory mechanisms & alternative splicing in autism spectrum disorders
Alternative splicing (AS) is a highly regulated mechanism that increases transcriptomic and proteomic diversity. AS occurs co-transcriptionally in the context of a dynamic chromatin environment that implicates changes in histone modifications. Genes linked to human neurodevelopmental processes are highly co-transcriptionally spliced in the human fetal frontal cortex. Dysregulation of AS has been associated with autism spectrum disorders (ASD). Chromatin regulators are overrepresented among high-risk confidence genes in ASD. However, how chromatin regulators modulate AS in relation to ASD pathogenesis is a gap in knowledge. We propose to study SETD2 which encodes a histone methyltransferase and is a major ASD genetic risk factor. SETD2 trimethylates lysine 36 on histone H3 (H3K36me3) regulating transcription and AS. However, whether SETD2 coordinates both transcription and AS in pathways relevant to ASD pathogenesis is unknown. We will use human neurons with pathogenic variants in SETD2 to: (1) Define the molecular mechanisms regulated by SETD2 by focusing on genomewide scale changes H3K36 methylation, as well as transcriptomic and AS alterations; and (2) Determine how the interplay between MRG15 and SETD2 regulates alternative splicing.  MRG15 is a chromodomain-containing protein that binds to H3K36me3, and acts as an “intermediary” between H3K36me3 and the AS machinery. We will define the interaction of MRG15 with splicing machinery and will determine changes in MRG15 genome-wide occupancy using epigenetic approaches. This work will be impactful to the study of ASD as the intersection between chromatin regulatory mechanisms and AS has been overlooked with respect to ASD pathogenesis.
PI: Sofia Lizarraga, Assistant Professor of Molecular Biology, Cell Biology and Biochemistry

Vaginal epithelial organoid models to study CD8 T cell differentiation
Resident Memory CD8 T cells (TRM) in the female reproductive tract (FRT) have a proven protective role against viral infections. As such positioning of CD8 TRM of high quantity and quality that are durably maintained is a key goal to achieve protective antiviral immunity in the FRT. Detailed understanding of molecular cues that guide FRT TRM differentiation is essential to attain this objective. Cells in the local environment i.e., reproductive mucosa is thought to be a big source of signals that shape CD8 TRM differentiation. Rodent models have long been used to uncover these molecular signals and local interactions. However, the complex nature of the in vivo vaginal microenvironment along with technical issues associated with inefficient FRT TRM isolation process have limited execution of high throughput studies focused on identifying these cellular communications. We have established a first of its’ kind in vitro three-dimensional vaginal epithelial organoid system (VEO) that accurately captures the features of in vivo multilayered stratified vaginal epithelium. By culturing these VEOs with CD8 T cells, we were able to induce CD8 TRM differentiation and the resulting TRM phenotypically and transcriptionally resembled antiviral TRM generated in mouse. Here we propose to leverage this VEO-CD8 coculture model to rapidly uncover fate-specifying transcription factors that govern TRM differentiation. The proposed study will establish a robust reductionist alternative to the in vivo mouse models currently in use and will provide novel mechanistic insights into epithelial-CD8 T cell interaction in the vaginal mucosa.
PI: Lalit Beura, Assistant Professor of Molecular Microbiology and Immunology

Germ cell toxicity of a low-dose phthalate mixture
Phthalic acid esters (phthalates) are a class of male reproductive toxicants used in the manufacture of certain plastics. Nearly all humans are exposed to small amounts of various phthalates, and at least ten phthalates are known male reproductive toxicants. Four phthalates are listed as priority substances by the Agency for Toxic Substances and Disease Control, and it has been proposed that phthalate risk should be assessed cumulatively (as a class), rather than for each individual chemical separately. Although phthalates are antiandrogenic, phthalate effects on germ cells are not mediated by androgen signaling, and there is reason to believe that altered germ cell development is directly linked to the most serious human health effects of early-life phthalate exposure, reduced fertility and increased risk of testicular cancer in adulthood. Here we will test whether a nine-phthalate mixture has cumulative (additive) effects on germ cell development. Timed pregnant rats will be exposed to a nine-phthalate mixture to generate dose-response data for multinucleated germ cells, a well-characterized histological biomarker of phthalate toxicity. We will also sequence fetal testis RNA to test the hypothesis that transcriptional changes are a more sensitive endpoint than histology and could be used for risk assessment. 
PI: Daniel Spade, Assistant Professor of Pathology and Laboratory Medicine

Vitamin A metabolic potential of human gut microbiome in health and disease
Vitamin A metabolite Retinoic Acid (RA) is key in regulating immune homeostasis and regeneration of the epithelial lining in the gut. Vitamin A is acquired exclusively from the diet and its conversion into RA, its active form was thus far thought to be performed exclusively by mammalian intrinsic vitamin A metabolic machinery. In a landmark recent study, we showed that bacteria residing in the murine gut can metabolize dietary Vitamin A into RA quite effectively. Crohn's disease is one of the two main types of inflammatory bowel disease (IBD), characterized by chronic inflammation of the gastrointestinal tract. Many studies have shown that individuals with Crohn's disease often exhibit alterations in the composition and diversity of their gut microbiome, a condition called dysbiosis. The vitamin A metabolic potential of the human gut microbiome has not been established so far. Importantly, whether vitamin A metabolism by the gut bacteria is altered and causative of disease pathogenesis is not known. In the current proposal, we want to determine if Vitamin A metabolism is a feature of a healthy human microbiome and if Vitamin A metabolic potential of gut microbiome can be linked to disease pathogenesis. To achieve this goal, we partnered with Prof. Jason Shapiro, who focuses on understanding IBD's natural history and immuno-microbial pathogenesis using patient-derived samples. Dr. Shapiro’s deep expertise in performing meaningful translational studies detailing microbiome and host-associated markers in IBD patients synergizes perfectly with our expertise in dissecting mechanistic underpinnings of host-microbiome interactions.
PI: Shipra Vaishnava,  Esther Elizabeth Brintzenhoff Associate Professor of Molecular Microbiology and Immunology
Co-PI: Jason Shapiro, Associate Professor of Pediatrics, Clinician Educator, Associate Professor of Medicine, Clinician Educator

Public Health 

Unlocking Rhode Island’s Pandemic Past
What can we learn from the pandemics of the past to inform our responses to the pandemics of future? This is the central question to be answered by the pilot project proposed in this application for research seed funding from the Office of the Vice President for Research. This historical epidemiological project aims to delve into the Rhode Island State Archives to, for the first time, leverage advances in artificial intelligence for handwriting recognition to transcribe and analyze scanned images of vital statistics records of deaths recorded before and during the Great Influenza Pandemic (1916–1920). By analyzing these historical records, we aim to explore temporal trends in pandemic diseases (e.g., cholera, influenza) and endemic diseases (e.g., tuberculosis, malaria); to investigate geographic patterns within Rhode Island’s cities and towns; and to examine differences across demographic subgroups. This project will provide valuable insights of the historical burden of infectious diseases, shedding light on disease dynamics that can inform contemporary public health strategies, assist in disease modeling, and help contextualize the current battle against infectious diseases. By examining historical vital statistics records, this project bridges the gap between past and present, enriching our understanding of epidemiological trends and contributing to the broader goal of the control of infectious diseases. Further, this work will set the foundation for future funding applications using archival vital statistics, census, and medical records to build a multigenerational cohort that allows us to understand the impacts of infectious diseases on the health and well-being of generations of Rhode Islanders.
PI: William Goedel, Assistant Professor of Epidemiology

Life Sciences and Public Health 

Infant Microbiota: Measuring the Influence of Breastfeeding and Tobacco Smoke Exposure
This study will assess differences in infant oral and gut microbiota by exposure to tobacco smoke and breastfeeding. This innovative study will expand the outcomes available for interventions combining breastfeeding and tobacco smoke avoidance, which will greatly improve the likelihood of successful research in this area. Addressing breastfeeding and tobacco smoke avoidance simultaneously is hypothesized to significantly improve the success of both breastfeeding and tobacco smoke avoidance behaviors with synergistic effects on infant health outcomes. Because resultant health outcomes occur much later, we are exploring earlier options to measure in a five-year R01. Infant gut and oral microbiota will be measured as proximal indicators of health risk and a potential mechanistic pathway between breastfeeding and tobacco smoke exposures in infancy and later health risks. Infant/mother dyads will be recruited late in pregnancy (>34 weeks gestation) from the Women and Infants Hospital clinic. Breastfeeding will be self-reported during the first week postpartum. Infant saliva and fecal samples will be collected during delivery admission and one week postpartum at home. Salivary cotinine will be analyzed as an objective measure of tobacco smoke exposure. Infant microbiota will be assessed by sequencing the V3–-V4 region of the 16S rRNA gene from the extracted DNA of saliva and fecal samples at both time points. This research builds on Dr. Risica’s prior successful work showing lower salivary cotinine in infants of mothers exposed to a perinatal newsletter/ tailored video intervention and Dr. Jamieson’s prior work exploring microbiota indicators of cancer. We anticipate submitting applications for R01 funding using this method as an objective outcome of behavioral interventions.
PI: Patricia Risica, Associate Professor of Behavioral and Social Sciences, Associate Professor of Epidemiology
Co-PI: Amanda Jamieson, Esther Elizabeth Brintzenhoff Associate Professor of Molecular Microbiology and Immunology