2022 RESEARCH SEED AWARDS

Physical SciencesLife and Medical Sciences | Life, Medical and Physical Sciences | Public Health | Research Seed Award Guidelines

Physical Sciences

High-Intensity Water-Assisted Laser Desorption-Ionization
The interaction of matter with high-intensity laser radiation can lead to the absorption of multiple photons. For ultrashort laser pulses, the sudden deposition of large amounts of energy creates non-equilibrium states that rapidly evolve in time. This project explores the outcome of the interaction of intense, femtosecond duration laser pulses with the surface of liquid water. In analogy to the well-known process of Matrix-Assisted Laser Desorption/Ionization, we anticipate that water can be ejected from the bulk and form a plume that carries with it any molecules and ions that were dissolved in the liquid. The absorption depth of water for high intensity pulses is very small, on the order of one micrometer, so that only a thin surface layer of water is ejected. In this project, we use non-equilibrium molecular dynamics simulations to simulate the laser ablation of analyte molecules suspended in a liquid water bath. Both coarse-grained models using the CHARMM molecular dynamics solver and fully atomistic simulations will be performed to probe the underlying fundamental physical processes driving the desorption-ionization process and to characterize the ejected plume composition. This project has important applications for mass spectrometry, which is a frequently used analytical method in research labs and in the field. Advances could lead to smaller and more compact instruments, as well as tools with unique capabilities.This research will advance Brown's position in the field through high-impact publications and by generating preliminary data that will lead to external funding to support collaborations with experimentalists from the Chemistry Department.
PI: Jesse Ault, Assistant Professor of Engineering

Life Beyond Earth: Determining the Habitability of Exoplanets
Our understanding of the universe has been revolutionized by the detections of exoplanet worlds beyond our Solar System. Specifically, these detections have informed us about the diversity and quantity of planetary systems in existence, how planets evolve, and where extraterrestrial life may exist beyond Earth. Yet these exoplanet worlds are sufficiently far away from the Earth that only minimal information on these worlds is available (e.g., mass, density, atmospheric composition). For this project, we will demonstrate that the expertise within DEEPS of modeling the linked tectonic, volcanic, and atmospheric evolution of planetary bodies coupled with the expertise of Physics in exoplanet/stellar observations can be used to reliably infer surface properties of exoplanets and identify environments capable of sustaining life. We will use the preliminary results of this project to apply to available external funding sources throughout NASA and NSF.
PI: Alex Evans, Assistant Professor of Earth, Environmental, and Planetary Sciences
Co-PIs: Stephen Parman, Associate Professor of Earth, Environmental, and Planetary Sciences; Daniel Ibarra, Assistant Professor of Earth, Environmental, and Planetary Sciences and Environment and Society; Gregory Tucker, Professor of Physics

Fiber-Optic Load Sensor for Investigating Laboratory Earthquake Processes
We propose to adapt a newly designed fiber-optic sensor to dramatically improve the resolution of stress measurement in our high-pressure deformation apparatus at high temperatures. Pilot data acquired at ambient temperature demonstrate the efficacy of the approach; here we request funds to test a modified design for experiments at pressures and temperatures where earthquakes occur in plate boundary subduction zones. Subduction zones host Earth’s largest and most damaging earthquakes and tsunamis. While characterization of earthquakes and slip behavior along subduction zones has advanced rapidly, our understanding of the underlying processes that control mechanics lags behind. The roles of pressure and temperature are central to this problem. Currently, the stress resolution in the apparatuses capable of reaching these conditions is not high enough to resolve the transient behavior that is key to understanding the relevant processes. Thus, models of these processes rely on data acquired at much lower pressure, where in situ devices can be incorporated in the experimental design. With our new fiber-optic cell, we have demonstrated the ability to improve stress resolution by approximately a factor of 30 (at ambient temperature) relative to other apparatuses capable of deforming samples at relevant pressures. With successful pilot data demonstrating the application of the fiber-optic sensor at high pressure temperature conditions, we will be poised to write competitive proposals to the NSF Geophysics panel and a new NSF initiative to study earthquake processes in subduction zones, and leverage continued support for our NSF funded rock deformation facility.
PI: Greg Hirth, Professor of Earth, Environmental, and Planetary Sciences

Synthetic Modeling Studies of the Repair of Iron-Sulfur Clusters in Redox Signaling
Proteins containing [Fe-S] clusters carry out multiple crucial biological functions, including gene regulation. This proposal addresses redox sensing by [Fe-S] clusters via a synthetic modeling approach. By studying the geometric and electronic structures, reactivity, and bonding properties of discrete biomimetic model complexes, we seek to understand strategies used in [Fe-S] regulatory proteins to battle against oxidative and nitrosative stress at the molecular level. Specifically, the goal of this Seed proposal is to understand the mechanisms by which a pH and redox sensor, mitoNEET, activates its function of [Fe-S] transfer in response to oxidative stress. The human mitoNEET protein has a unique asymmetric [2Fe-2S] cluster ligated by three cysteines and one histidine. MitoNEET transfers its own [2Fe-2S] cofactors to its partner apo-proteins when the [2Fe-2S] center is oxidized (e.g., under oxidative stress) and the His ligand is protonated. However, it is not well understood what causes this redox-dependent cluster transfer upon protonation and how the [Fe-S] core is transferred without complete disassembly. In our preliminary studies, we developed a novel synthetic method to prepare site-differentiated [2Fe-2S] clusters bearing a neutral N-donor ligand as a model system for the unstable mitoNEET intermediate en route to cluster transfer. Our proposed studies include the elucidation of the electronic structures of mitoNEET models to understand how the presence of a neutral N-donor ligand influences the neighboring Fe-S(sulfide) and Fe-S(thiolate) bonds. We will also examine the feasibility of [Fe-S] transfer from mitoNEET analogs to another chelate without disassembly of the [Fe-S] core.
PI: Eunsuk Kim, Associate Professor of Chemistry

Using resistively detected microwave resonance to study quantum material and develop 2D material-based quantum-bit
This proposal has two main focuses: (i) develop the ability to directly probe and characterize spin excitations in 2D material structures using resistively detected microwave resonance techniques; (ii) develop necessary experimental schemes to couple microwave to 2D material-based quantum-bit (qubit) and realize fundamental qubit control. Observation of microwave resonance in 2D material structures has remained elusive since the discovery of graphene almost 2 decades ago. Recently, we have demonstrated for the first time that microwave resonance in 2D material structure can be resistively detected. This experimental breakthrough is achieved by introducing spin-orbit coupling to a flat energy band of graphene moiré structures. The ability to coupling microwave radiation to the spin structure of 2D material will establish a powerful addition to the toolbox of condensed matter research, which will be widely adopted by research groups worldwide. At the same time, this technique could enable experimental control on quantum-bit based on 2D material structures, which is the essential ingredient for various schemes of quantum computation. The support of the Seed award will allow us to achieve three main outcomes in a reasonable time frame: (1) we will build a microwave setup in my research lab at Brown University; (2) we will further develop the microwave resonance technique by defining the parameter range for optimal operation, which will establish resistively detected microwave resonance a powerful tool for condensed matter research; (3) we will demonstrate coupling between microwave and electrons in the quantum dot device geometry and perform basic qubit controls.
PI: Jia Leo Li, Assistant Professor of Physics
Co-PI: Vesna Mitrovic, Professor of Physics

Statistics of Classical Nonlinear Dynamics by Quantum Computation
We will use quantum computers to find the statistics of classical nonlinear dynamical systems far more efficiently than is possible with classical computers. Dynamical systems of interest range from those describing chemical reactions to climate models. We will use high quality trapped-ion based quantum computers developed by IonQ, Inc. (we have received time on their machines through the IonQ research credit program). To take full advantage of this resource we are requesting seed funding to support a PhD student based in the Departments of Chemistry or Physics to work on implementing quantum linear algebra algorithms on the IonQ computer to complete the project. We will then be in a strong position to apply for external funding, helping to fulfill Brown’s ambition to develop strengths in quantum information science.
PI: John Marston, Professor of Physics
Co-PI: Brenda Rubenstein, Associate Professor of Chemistry

Engineering a new generation of bio-inspired autonomous underwater robotic sensors
Metachronal swimming is a propulsive gait allowing small aquatic organisms of O(10) mm to perform up to 1000-meter-long vertical migrations in the ocean. By sequentially beating appendage pairs and modulating the forces on their body while swimming, marine crustaceans (e.g., krill) can effectively sustain long-distance migrations. However, the mechanism of metachronal swimming is poorly understood due to the small size of the organism and the lack of force and flow field measurements. In this project we will combine standard experimental techniques in fluid mechanics and unique robotic models to answer fundamental scientific questions regarding thrust generation and flow-structure interactions. Using our unique metachronal robotic model, we reproduce the swimming kinematics of Antarctic krill, an abundant animal species of Earth. We will combine flow visualization with force measurements to provide a quantitative evaluation of the links between swimming kinematics, force production, and vortex dynamics during forward swimming. Our results will lay the foundation for the development of a new generation of underwater robotic platforms that can effectively perform essential underwater activities, including exploration, targeted sensing, and filtering of micro-particles.
PI: Monica Martinez Wilhelmus, Assistant Professor of Engineering

Enabling mobility in terahertz networks
One of the challenging aspects of engineering a wireless network at very high frequencies is to determine how to maintain a high-quality link even when the receiver is in motion. In existing 4G wireless systems, which operate at lower frequencies below 6 GHz, this problem is addressed by using quasi-omnidirectional broadcasts. If the signal is broadcast in all directions, then a receiver is always within the broadcast sector of the base station or tower, and can move freely without worrying about losing the connection. However, at higher frequencies, particularly those above 100 GHz that are under increasingly intense investigation for use in future (beyond 5G) systems, this problem is much more challenging. At these high frequencies, connections will need to rely not on omnidirectional broadcasts, but instead on very directional pencil-like beams. To maintain a link even when the receiver is mobile, this beam must be dynamically steered so that it continuously points in the correct direction. To date, no realistic solution to this challenge has been identified; as a result, beam steering is now a primary concern in the design of systems that will operate in this frequency range. In the proposed research program, we will explore the use of a space-time-modulated metasurface, a micro-antenna array subject to a complex temporal and spatial modulation pattern, to provide this beam steering functionality. If successful, our results will establish a new paradigm for the design of terahertz wireless links.
PI: Daniel Mittleman, Professor of Engineering

Social Video Verification from Multiple Cameras
Deepfakes can spread misinformation, defamation, and propaganda by faking videos of events, like public speaker or protests. We assume that future deepfakes will be visually indistinguishable from real video and will also fool current deepfake detection methods. As such, we posit a social verification system that instead validates the truth of an event via a set of videos captured by multiple different people. To confirm which, if any, videos are being faked at any point in time, we propose to embed videos within the model space of learned generative deep neural networks and enforce multi-camera constraints that factor the change in appearance across camera views. Then, we propose to check for inconsistent appearance across videos using graph analysis, where each camera is a node and where edge weights are formed from the embedding distance. Initially, we will focus on facial appearance as it is a high-value fake target; then, given future funding generated from this seed, we will expand our remit to cover human body and multiple human interaction appearance. Overall, this project combines socially responsible computing ideas with new techniques in multi-camera appearance modeling to provide new tools to combat deepfakes.
PI: James Tompkin, Assistant Professor of Computer Science

CO2 Capture by Conversion: Carbon-based Chemicals from Carbonate Reduction
A dream technology would capture CO2 directly from the air and use it as a feedstock to produce renewable carbon-based fuels and chemicals, rather than relying on fossil fuels. Nearly all approaches to date have separated CO2 capture and CO2 conversion into two distinct steps, but the compounding inefficiencies make the process impractical. This proposal targets a key step in the CO2 capture/conversion processes by studying catalytic approaches to carbonate reduction. CO2 can be easily captured by an alkaline solution and by converting CO2 to a carbonate, but this carbonate is difficult to reduce. In this project, we will first react (saturate) atmospheric CO2 in an alcoholic alkaline solution to produce an alkylcarbonate, and will then reduce this carbonate via either electrochemical or chemical reduction method. Aided by computational design, we will prepare and study Cu-based nanoparticle catalysts to reduce the carbonate to an active form of carbon. Our goal is to demonstrate a scientifically viable catalytic approach to bridge CO2 capture and conversion. The research will provide promising solutions to climate change and sustainability issues associated with CO2 emissions.
PI: Shouheng Sun, Vernon K. Krieble Professor of Chemistry, Professor of Engineering
Co-PI: Andrew Peterson, Associate Professor of Engineering

Life and Medical Sciences

Development of a Massively Parallel Reporter Screen in Whole Fish
The breeding program that generates farm raised Atlantic Salmon is in its 17th generation. A growing awareness of the environmental impact of aquaculture has driven regulation reducing the use of outdoor pens. Here, we propose the application of state-of-the-art genomic technology to animal breeding to bring fish to market faster and reduce the use of outdoor pens. A successful breed/strain contains naturally occurring genetic variations that increase or decrease the levels of genes that positively influence growth, resistance to disease/cold, and physio-metabolic qualities such as adiposity. While many genes influence salmon commercial appeal, it is clear that increased growth hormone (GH) production is desirable as it reduces growth time. GH, along with antifreeze proteins (AFP) has been the target of all transgenic aquaculture lines developed for research purposes in the past 30 years. Here, we propose technology that will screen every possible variation in the salmon growth hormone promoter using a high throughput massively parallel reporter assay. Briefly, this technique will determine the effect of every possible variant that could occur naturally and measure how it a) affects growth hormone level and b) retains proper growth hormone expression (i.e. remains expressed only in the pituitary gland). This proposal represents the first proof of principle application of a massively parallel reporter system in a model organism (zebrafish). Variants that increase GH in the reporter system and transgene will be tested in a “salmonized’ zebrafish.
PI: William Fairbrother, Professor of Biology
Co-PI: Jessica Plavicki, Manning Assistant Professor of Pathology and Laboratory Medicine

How does locus-specific DNA amplification override DNA re-replication controls in the genome?
The cell utilizes multiple controls to ensure that each origin of replication (ORI) is activated only once per cell cycle. When these controls are overridden and an origin fires more than once, local DNA amplification results. DNA amplification is a hallmark of cancer, but the mechanism of the initiating events that drive re-replication is unknown and cannot be studied in cultured cancer cells. Instead, we are using the fly Sciara that is one of only two known examples where locus-specific intrachromosomal DNA re-replication results in DNA amplification at 18 “DNA puffs” in larval salivary gland polytene chromosomes as a normal developmental event. We have focused on DNA puff II/9A, the most highly amplified of the DNA puffs. We have mapped the II/9A ORI of re-replication, a DNase hypersensitive site (DHS) 600 bp upstream and bent DNA between the DHS and the ORI. Injection of the steroid hormone ecdysone induces premature DNA amplification. Our ChIP and CUT&RUN experiments revealed that the ecdysone receptor (EcR) binds to the DHS that we hypothesize loops back to contact the ORI since EcR co-immunoprecipitates the origin recognition complex that is part of the pre-replication complex bound to the ORI. We propose to develop a new method using CRISPR for site-directed mutagenesis for insertion or deletion of large stretches of DNA to test if deletion of the DHS abrogates DNA amplification. The results will be of significance to the fields of DNA replication, cancer, and genomic engineering (“editing”), underscoring Brown’s support of conceptual and technical advances.
PI: Susan Gerbi, George D. Eggleston Professor of Biochemistry

Axon guidance through changes in growth cone membrane potential
In order to produce a functioning nervous system, neurons must form precise connections with each other during embryonic development. The guidance of growing axons to their correct targets is central to sculpting neuronal connectivity, and understanding this process is critical, as neuronal miswiring can cause neural circuit dysfunction and disease. Our project investigates if molecular cues instruct axon pathfinding by triggering changes in the axonal membrane potential. We propose to employ and improve our cutting-edge, genetically encoded voltage sensors to monitor the membrane potential of axons in response to various attractive and repulsive guidance cues, with the goal of identifying patterns of membrane de- or hyperpolarization that dictate the axonal response to attractants versus repellants. This will lay the foundation for a long-term plan to investigate the causal relationship between guidance cues, axonal membrane potential, and axon steering. Our work will uncover fundamental mechanisms of axon guidance and neural circuit assembly, which is essential for understanding disorders of brain wiring and developing therapeutic approaches for the restoration of damaged neuronal connections after physical injury or onset of neurodegenerative disease.
PI: Alexander Jaworski, June G. Zimmerman Associate Professor of Brain Science
Co-PI: Ahmed Abdelfattah, Robert J. and Nancy D. Carney University Assistant Professor of Brain Science

Establishing a Drosophila model for opioid self-administration
The U.S. is in the midst of an opioid epidemic and overdose crisis, which has only been exacerbated by the COVID-19 pandemic. It is imperative that the health community have access to the most effective treatments to help solve this epidemic. However, effective treatment development requires a better understanding of the neurobiology of opioid use and dependency. The lasting physiological effects of opiates on reward memory circuits contribute to cravings for the drug and change the brain’s response to other drugs of abuse. Opiate drugs bind to opioid receptors (ORs) in the brain, hijacking a complex endogenous neuromodulatory system. In mammals, µ opioid receptors (µORs) are the key molecular targets for the biological effects of clinically useful and abused opioids. The sheer number and heterogeneity of neurons within reward circuits, combined with their elaborate connectivity, has prevented a deeper understanding of the identity of µOR expressing circuits. A small but sophisticated brain and impressive array of neurogenetic tools for in vivo analysis have proven the fruit fly, Drosophila melanogaster, to be an ideal model for discovery of novel mechanisms underlying the effects of drugs of abuse on the brain. Here we propose to establish Drosophila as an effective model to understand the neural and molecular mechanisms underlying the motivation to seek the high-potency synthetic opioid fentanyl. Our goal is to use a functional neurogenetic approach to identify the Drosophila µOR and map the neural circuits through which this receptor is eliciting fentanyl-induced behavioral responses.
PI: Karla Kaun, Associate Professor of Neuroscience

Identification of LRRC15 as a novel restriction factor for SARS-CoV-2
SARS-CoV-2 infection relies on the ACE2 receptor for its cellular entry. Although cellular entry of the virus is the primary target for antiviral therapeutics, it is understudied how entry of SARS-CoV-2 is regulated. Here we show that Leucine-rich repeat-containing protein 15 (LRRC15) is a novel restriction factor for SARS-CoV-2. Using a focused CRISPR activation screening targeting all known cellular surface proteins, we identified LRRC15 as a cellular restriction factor that binds to Spike protein of SARS-CoV-2. Expression of LRRC15 in SARS-CoV-2 permissive cell lines strongly inhibits the infectivity of Spike-pseudo-typed VSV but not G-pseudo-typed VSV, indicating the restriction activity is coronavirus-specific. The binding between Spike and LRRC15 is confirmed by a cell-free binding assay. In this proposal, we will examine the physiological role of LRRC15 in restricting SARS-CoV-2 infection with two specific aims. Aim 1, we will define the specificity of the restriction activity of LRRC15 across human coronaviruses including SARS-CoV-1, MERS, and seasonal coronaviruses. Aim 2, we will test whether LRRC15 is associated with severity of disease progress, robustness of viral replication, and asymptomatic/symptomatic disease outcome in patients using publicly available datasets. This study will provide one of the first human cellular restriction factors regulating SARS-CoV-2 infection and shed an insight into novel design for therapeutics.
PI: Sanghyun Lee, Assistant Professor of Molecular Microbiology and Immunology

Targeting purinergic receptors in synaptic glia to treat ALS
Amyotrophic Lateral Sclerosis (ALS) is an adult-onset neurodegenerative disease that causes paralysis and death within 5 years of diagnosis. Although the disease has been clinically recognized for over 140 years, effective therapies for ALS have yet to be developed. Riluzole and Radicava (Edaravone), the only therapies approved for ALS, are minimally effective, only extending life by several months. A hallmark of ALS is early and progressive destruction of the neuromuscular junction (NMJ), the peripheral synapse that controls all skeletal muscles and thus voluntary movements. Development of treatments that target the NMJ have been hampered by the paucity of information about molecular mechanisms critical for NMJ maintenance and repair. To address this gap, our lab has focused on the molecular composition of synaptic glial cells of the NMJ, which have been largely overlooked. We have discovered that these cells express three purinergic receptors with well-characterized roles in synaptic maintenance in the central nervous system. In this work, we will test the hypothesis that modulating the activity of these purinergic receptors, using FDA-approved pharmacological agents, will mitigate NMJ degeneration in a mouse model of ALS. The preclinical data arising from this work may set the stage to target purinergic receptors to treat patients suffering with ALS.
PI: Gregorio Valdez, GLF Translational Associate Professor of Molecular Biology, Cell Biology and Biochemistry

An extracellular Prion-like protein is essential for fertilization
Prions are a type of protein domain that can trigger normal proteins to fold abnormally. Human proteins with domains that resemble yeast prions form protein aggregates that cause cell death in neurodegenerative diseases. Yet, these same domains are able to form dynamic liquid-like droplets that contribute to the formation of membraneless organelles including numerous cytoplasmic and nuclear compartments. We recently learned that Bindin from sperm of a sea urchin has two prion-like domains, is secreted, and is essential for fertilization. Extracellular prions are very unusual (and no extracellular eukaryotic prion-like proteins or prion-like phase separated assemblies have been described in detail). These prion-like domains have highly variable sequences between species, thought to be species-specific recognition elements. We will dissect the prion-like domains and test their role in sperm-egg interaction and species specificity by in vitro egg interaction. Three features make this work of high impact: 1) Is the prion-like domain essential for its function? We currently know only that the Bindin product is essential. 2) Does the prion-like domain confer species-specific sperm-egg recognition? Production of the prion-like domain and modifications thereof will be used to test egg interactions species specifically. 3) Does the prion-like domain self-assemble into extracellular liquids, gels, or aggregates – the spectrum of states seen for intracellular prion-like domains? This preliminary work will have high impact in several fields of biomedical research and clinical application, breaking new ground in the molecular mechanism of critical steps in fertilization and describing the unexplored atomic details of this extracellular assembly.
PI: Gary Wessel, Professor of Biology
Co-PI: Nicolas Fawzi, Associate Professor of Molecular Biology, Cell Biology and Biotechnology

Life, Medical and Physical Sciences 

Development of Quantum Magnetic Tunneling Junction Sensor Arrays for Magnetoencephalography (MEG)
We aim to develop a revolutionary quantum magnetic gradiometer designed to non-invasively register femtoTesla (fT) scale magnetic fields from the human brain and examine its operating characteristics during simple voluntary movements and visual stimulation. The sensor, with its miniaturized size, will substantially exceed the spatial resolution of existing systems, operate at room temperature, will not require expensive magnetic shielding, can be used untethered, thus, in the field, and the expected system will have a far lower initial purchase price and lower maintenance costs than available magnetoencephalographic (MEG) systems. These features should expand the utility, accuracy, and accessibility of magnetic field recording technology for human neuroscience applications to advance our understanding of human brain function in health and disease.
PI: Gang Xiao, Professor of Physics, Professor of Engineering
Co-PI: Jerome Sanes, Professor of Neuroscience

Vector beam pulse oximetry
The onset of COVID-19 has made the rapid and accurate detection of irregular oxygen saturation levels important in curbing the number of resulting deaths. As a result, the past year has seen significant interest in traditional photoplethysmography (PPG) technology, namely pulse oximeters, to monitor oxygen saturation levels. Moreover, there has been an increased demand for smartwatches and other wearables that can accurately carry out on-demand PPG measurements. However, several studies have reported that this optical technique overestimates the actual oxyhemoglobin saturation in patients with darker skin tones, leading to silent hypoxia and a potentially disproportionately higher number of deaths for black and brown patients, in particular. This work will focus on developing a novel PPG technique to mitigate the issue of skin tone, and other related skin-based confounding effects such as wrinkles and tattoos, using an optical polarization vector beam. Compared to other algorithms that exploit polarization to suppress skin effects and increase accuracy, our approach enables multiple polarization measurements in parallel, thereby offering increased speed.
PI: Kimani Toussaint, Professor of Engineering

Public Health

Safety, feasibility, and acceptability of MDMA-assisted therapy for the treatment of co-occurring posttraumatic stress disorder and alcohol use disorders in combat veterans
Co-occurring PTSD and alcohol use disorder (PTSD-AUD) is common following combat and associated with more severe symptomatology, increased suicidality, and poorer response to treatment than either disorder alone. Available PTSD-AUD treatments effectively treat only a fraction of people who engage in them for adequate dose and duration, leading to growing interest in alternative medications, including psychedelics. The combined neurobiological effects of MDMA increase compassion, reduce defenses and fear of emotional injury, and enhance communication and introspection, making MDMA-AT especially useful for treating PTSD-AUD. This pilot trial will be the first to assess feasibility and acceptability of MDMA-assisted psychotherapy (MDMA-AT) in veterans with combat-related PTSD and AUD (N=20) and will result in a new interdisciplinary collaboration at Brown. Participants will be recruited via social media and clinician referrals and will complete an initial screen and baseline appointment including informed consent. Eligible participants will receive MDMA-AT, including three Experimental Sessions with MDMA administration that will be conducted under established protocols. Follow-up data will be collected at post-treatment and at one-month. This project will allow us to: 1) assemble a research team including the training of two MDMA-AT clinicians, 2) determine the feasibility of recruitment, 3) determine the acceptability of and safety of MDMA-AT, 4) provide preliminary evidence of the effects of MDMA-AT, and 5) refine study procedures in preparation for a fully powered RCT to test the effectiveness of MDMA-AT for PTSD-AUD. This collaboration will help to position Brown at the forefront of psychedelic research for common and impairing mental health problems.
PI: Carolina Hass-Koffler, Associate Professor of Psychiatry and Human Behavior and Associate Professor of Behavioral and Social Sciences 
Co-PI: Erica Eaton, Assistant Professor of Psychiatry and Human Behavior (Research), Assistant Professor of Behavioral and Social Sciences (Research)

Observational study of the safety, accuracy and usability of digital diagnosis apps in primary care and for TIA and stroke patients
Patients commonly search their symptoms and diseases online, and mobile phone apps for digital diagnosis (“Symptom Checkers”, SC) are used by >40 million US patients annually. However there is minimal evidence from real patient use in the community on accuracy of diagnosis or triage, patient safety, or usability. This research builds on collaborations between Brown Center for Biomedical Informatics, The Rhode Island Hospital (RIH) Emergency Department (ED) and Brown Medicine to research the role and potential impact of symptom checker (SC) apps used by patient seeking urgent primary care, and the performance of SCs and new algorithms for diagnosis of transient ischemic attacks (TIA) and stroke. AIM 1 will extend an evaluation of a leading SC from Ada Health, with use by 200 patients requesting urgent care appointments at Brown Medicine, including a usability questionnaire, prior to their appointment. Reviews of the symptom data and results from the App and the physician who sees the patient will allow comparison of diagnosis and triage. AIM 2 will analyze the accuracy of symptom checkers including Ada and develop new algorithms using 2 data sets of symptoms of patients presenting with TIA or stroke - high risk diseases with hard to recognize symptoms, requiring urgent treatment. Data sets include 1800 patients admitted with suspected TIA to the clinical observation unit, RIH, and 100,000 patient consults with Ada App, and possible stroke diagnosis. We will study diagnostic performance of multiple SCs and new algorithms including effects of age and gender, Quick patient recognition of stroke and prompt arrival in the ED should reduce the current high morbidity and mortality. 
PI: Hamish Fraser, Associate Professor of Medical Science