A prototype flight for the GRAMS project

This grant is for the prototype balloon flight of the GRAMS (Gamma-Ray and AntiMatter Survey) Project. GRAMS mission aims to deliver unprecedented sensitivities to astrophysical observations with MeV gamma rays and indirect dark matter searches with antimatter using a cost-effective, large-scale LArTPC (Liquid Argon Time Projection Chamber) detector. We will build and optimize a small-scale detector, MiniGRAMS, and demonstrate its performance in the balloon flight scheduled in late 2025 or early 2026.

Framework for Converting Gate-Based Quantum Computing Models to Quantum Annealing Models for Large-Scale Electronic Structure and Dynamics Simulations

Simulating the electronic structure of molecular systems using noisy intermediate-scale quantum devices is one of the most promising applications of quantum computing. Large-scale electronic structure and dynamics simulations, such as excited-state simulations of large molecules or a large number of molecules, are instrumental to the development of next-generation technology for energy applications. In this project, we will develop a framework that efficiently translates quantum algorithms from a gate-based quantum computing model to one that can be efficiently run on a near-term quantum annealer to enable large-scale electronic structure theory simulations across different quantum computing architectures. These algorithms will offer an adaptive approach to predicting both the ground and excited electronic states of molecules, which has direct applications in simulating the photodynamics of macromolecules and materials related to but not limited to solar energy harvesting and conversions.

Amgen Biotech Experience (ABE) Massachusetts

The ABE MA is a multiple year STEM grant to bring biotechnology to the high school classrooms throughout MA. It consists of professional development for teachers and deployment of curriculum into high school classrooms.

mCDR 2023: Developing a coupled benthic-pelagic biogeochemical model to evaluate the effectiveness of mCDR interventions

Deep cuts to emissions across all sectors are needed in order to limit global warming to 1.5˚C to 2˚C above preindustrial values. If zero emission is ever to be achieved, further implementation of carbon dioxide removal (CDR) strategies are also necessary to offset emissions from hard-to- abate sources. This project will focus on two CDR approaches with direct influence on the ocean sediment: seaweed farming and further sinking into the deep ocean and restoration of “blue carbon” coastal ecosystem, more specifically cessation of bottom trawling to preserve sediment carbon. We will do so by developing a new model for the ocean sediment and benthos that can be coupled to existing ocean models to simulate these strategies and quantify their effect on the carbon cycle as well as understand potential feedbacks that could impact the ocean ecosystem.

Experimental Particle Physics Research at High Energies

This grant supports the work of three faculty members at Northeastern University (Barberis, Orimoto, and Wood) plus several postdoctoral researchers and students on the CMS experiment at the CERN Large Hadron Collider (LHC). The program includes analysis of CMS data in carefully chosen physics topics, including searches for leptoquarks and for the production of pairs of Higgs bosons, and measurements of standard model production of W+jets and ZZ pairs. It also includes support and development of the current detector for taking new data, and development of instrumentation upgrades that will enable CMS to exploit future high luminosity running of the LHC(HL-LHC). The group has leading roles in the operations and upgrades of the CMS Muon system, the muon trigger, the electromagnetic calorimeter, and the new MIP timing detector.

DMREF: Deep learning guided twistronics for self-assembled quantum optoelectronics

This grant is from the NSF Designing Materials to Revolutionize and Engineer our Future (DMREF) program and aims to accelerate the discovery and deployment of multi-layer twisted 2D systems for quantum optoelectronics.

Understanding Mediating and Moderating Factors that Determine Transfer of Working Memory Training

This proposal aims to improve the rigor and reproducibility of research on plasticity in human working memory (WM), and related executive functions (EFs) in adolescent youth. We address a critical gap between research and practice that is characterized by a growing commercial space marketing cognitive training approaches (with WM being one of the most common targets), which are particularly catering to typically developing children and those diagnosed with ADHD to improve mental health and scholastic performance. However, despite expansive literature, there exists limited basic research on WM and EF training in adolescents, and both methods and findings are mixed across studies. Here, we address these significant gaps that pose obstacles to understanding interventions’ reliability and validity by collecting a large-scale open dataset that compares different training approaches on a common set of outcome measures.

ACS Medicinal Chemistry Predoctoral Fellowship

This fellowship funds a year of research in the field of medicinal chemistry through a sponsorship by Genentech.

Integrative biophysical modeling for collective tissue mechanics

Organ surfaces, made of epithelial or endothelial cells, serve as physical barriers. These cells are generally static but can transition to a dynamic, migratory state during physiological processes like development and repair. Traditional studies focus on these cells in 2D flat surfaces, which doesn't translate well to natural epithelia that often have curved geometries and varied topologies like spheres and tubes. Key questions remain about how curvature affects cell collective movement and the mechanics of multilayered tissues like mammalian epidermis. These issues are particularly critical during epidermal development, where cues and timescale-dependent mechanics are not well understood. To address these gaps, I plan to develop computational models that go beyond the conventional 2D approach, incorporating curved and multilayered 3D surfaces. This will include new models exploring the biomechanical relationship between nuclear shapes and cell proliferation.

Behavioral and neurocognitive mechanisms linking peer victimization to adolescent psychopathology

Adolescence is a period of heightened vulnerability for many forms of psychopathology. This vulnerability comes at a time when emotional and physiological responses to peer rejection are elevated, rendering peer victimization particularly damaging. Despite the strong links between peer victimization and internalizing problems during adolescence, the behavioral and neural mechanisms underlying this association remain unclear. The proposed project will test a novel conceptual model, whereby two underlying dimensions of peer victimization, peer threat (e.g., presence of negative social experiences, like rejection) and peer deprivation (e.g., absence of positive social experiences, like ostracism) differentially shape neurocognitive processes and social behaviors that have relevance for psychopathology. We test this conceptual model using experimental and observational approaches in an intensive longitudinal design, including experimental and fMRI tasks, digital phenotyping, and predictive modeling approaches. This work is a necessary first step in developing targeted interventions to mitigate the effects of peer victimization during adolescence.

Empirical Power Analysis Tool for fMRI

Functional magnetic resonance imaging (fMRI) research has transformed our understanding of human brain function and disease, but recent work has exposed an endemic lack of statistical power (i.e., ability to detect effects of interest) and a need for power analysis tools that meet the demands of the typical user. We propose to create a web-based power calculator tailored to typical fMRI studies that only requires the user to specify information readily available to them. By enabling researchers to more easily and accurately plan studies for desired levels of power, this power calculator will promote more robust and reproducible findings in the field.

Seed collection and propagation of eelgrass (Zostera marina) for restoration efforts

This project funds a research assistant to collect and maintain a supply of eelgrass seeds that can be used in restoration efforts. They will also help MA DMF develop best practices for seed collection, storage, and distribution in support of state-wide restoration projects.

STING agonist drug delivery formulations synergize with PARPi to treat resistant, metastatic advanced breast cancer

The objective of this work is to generate clinically relevant data to support the use of PARPi in combination with local and systemic drug delivery platforms of STING agonists in order to treat metastatic, resistant breast cancer.

Probing negative affect circuits in humans using 7T fMRI

Negative mood is a common feature of anxiety, depression, bipolar disorder, and schizophrenia, which inflict immeasurable human suffering along with a combined economic burden of $600 billion in the US each year. The proposed research promises to deliver a new paradigm for studying the brain basis of negative affect, with the ultimate goal of developing targeted treatments for negative mood, a hallmark feature of many mental illnesses.

A seascape of adaptations - Testing models that predict performance in multivariate environments

We are studying the adaptation of eelgrass to future ocean conditions in the Baltic Sea.

Collaborative Research: Enzyme-Mimicking Catalysts for Cellulose Processing

Lignocellulosic biomass from plants is a renewable, carbon-neutral material produced at a scale of 170-200 billion tons per year. The depolymerization of cellulose is a key step in biomass conversion, but it is challenged by the stability and crystalline nature of the cellulose fibers. We will develop synthetic catalysts based on molecularly imprinted nanoparticles that mimic endocellulase, exocellulase, and beta-glucosidase for the efficient hydrolysis of cellulose.

Fractionated photoimmunotherapy to harness low-dose immunostimulation in ovarian cancer

The Spring research group, in collaboration with the Enderling lab at Moffit Cancer Center, has been awarded a Physical Sciences Oncology Network grant (NCI U01 CA280849; ~$2.7M) titled "Fractionated photoimmunotherapy to harness low-dose immunostimulation in ovarian cancer". The project will harness an integrated experimental—mathematical oncology approach to decipher how to best harness immune sparing and immune stimulation of fractionated photoimmunotherapy to personalize treatments for advanced or recurrent ovarian cancer patients with presently dismal survival rates.

DMS/NIGMS 2: Regulation of Cellular Stemness during the Epithelial-Mesenchymal Transition (EMT)

We propose a joint theoretical/experimental research program to address cell-fate trajectories that occur during induction of EMT, the epithelial-mesenchymal transition. Specifically. recent efforts have indicated that epithelial cells can either undergo direct reprogramming to mesenchymal states or alternatively become more stem-like and exhibit hybrid E/M properties. Based on our preliminary investigations, we will use state-of-the-art single cell measurement technology together with advanced mathematical modelling frameworks to understand how cells choose specific fates and to quantitatively unravel the genetic and epigenetic dynamics that leads these cells along their particular trajectories. We will develop new mathematical concepts such as the role of frustration in cell fate networks, the effects of global competition on epigenetic interactions, the role of confluency in governing cell-cell interactions, and the introduction of model-based ideas into trajectory inference, as part of our investigation.

Transcendental fiber functors, shift of argument algebras and Riemann-Hilbert correspondence for q-difference equations

This project stems from the recent discovery that quantum groups naturally arise from the Stokes data of differential equations associated to classical symmetries. The main goals are to further explore this bridge between classical and quantum symmetries. Of particular interest is the extension to difference equations, which are natural discretisations of differential equations, and whose Stokes data are not well-understood beyond the one-variable case. Another important direction will the study of the integrable systems, or constants of motion, corresponding to these differential and difference equations. The project will provide research training opportunities for graduate students.

Microlocal analysis and singularities

Degenerations and singularity formations play important roles in the study of differential geometry and arise naturally in multiple other areas of mathematics, including, algebraic geometry, mathematical physics, number theory, and representation theory. This project concerns the geometry of singularities and has interesting connections with an array of disciplines including modeling of electromagnetic systems, gauge theory and string theory. Building on her track record, the PI plans to use effective techniques to solve a wide variety of problems and discover new and sharper analytic results. Alongside her research, the PI will engage in various outreach activities, with a focus on fostering mentoring networks for undergraduate and graduate students.

Activation of Benzoxaborole Prodrug AN15368, a Clinical Candidate for Chagas Disease

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is endemic in the Americas, but has also globalized due to human migration. Despite being one of the major causes of infection-induced heart disease worldwide, current therapies for Chagas disease have inconsistent efficacy and frequent side effects. A major contributor to treatment failure is thought to be the transiently dormant intracellular forms of T. cruzi that are resistant to otherwise highly effective trypanocidal compounds. The newly discovered benzoxaborole AN15368 represents the first extensively validated and safe clinical candidate for the treatment of Chagas disease. AN15368 acts as a prodrug that requires cleavage by parasite serine carboxypeptidases (TcCBPs) to yield the active metabolite. This proposal aims to gain additional understanding of this processing step for AN15368 as a prodrug, as well as to assess the potential for acquired resistance as this compound proceeds toward human clinical trials.

Unidirectional single-file transport of full-length proteins through a nanopore

In this multi-PI project between the Wanunu Lab (Northeastern), Chen Lab (UMass Amherst), Aksimentiev Lab (Urbana Champaign), and Niederweis Lab (U Alabama), we will develop a next-generation single-molecule protein sequencer based on engineered high-resolution nanopores. Key reference to cite: Yu et al., Unidirectional single-file transport of full-length proteins through a nanopore, Nature Biotechnology, 2023. DOI: https://doi.org/10.1038/s41587-022-01598-3

Synthesis of motif and symmetry for accelerated learning, discovery, and design of electronic structures for energy conversion applications

The goal of the proposed work is to develop the data-driven approach based on structure motifs and orbital symmetries to discovery and design inorganic semiconductor compounds with optimal electronic structures for energy conversion applications. Objectives are: (i) to develop a framework toward the universal description of structure motifs as well as crystal/orbital symmetries in inorganic compounds; (ii) to accelerate the motif and symmetry based discovery and design of oxide and layered semiconductor compounds with optimal electronic properties for energy conversion applications; iii) to enable the effective learning of structure motifs and orbital symmetries through the combined use of national language processing, graph theory, and deep learning.

Categorical centers, cactus actions, and diagram algebras

This project delves into several research directions within representation theory, which is the mathematical framework for studying objects through their symmetries and the operations which preserve them. Such operations can carry a classical, or even more intriguingly a quantum algebraic structure. Originally appearing in physical models within statistical mechanics and quantum integrable systems, quantum groups and the theory surrounding them are now a thriving source of uncovering new mathematical principles. This project will develop a richer understanding of this theory by building a common ground for combining algebraic, combinatorial, and higher-structural categorical techniques for the study of quantum groups and associated diagram algebras. This will lead to a more unified approach and provide connections between several areas of mathematics, as well as potential physical applications. The project will involve the participation of undergraduate students and create opportunities for discussion and collaboration among early-career researchers.

Genetic assessment and native plant production for the US Army Corps of Engineers BAA 6 Belle Isle Project, Boston, MA

Genetic variation can be critical for population performance and resilience, yet it is seldom accounted for in habitat restoration efforts. This project will assess the genetic diversity of the dominant salt marsh plants Spartina alterniflora and Spartina patens in natural marshes in and around Belle Isle Marsh, MA. We will also produce local stocks of each of these species from seed and compare their genetic and phenotypic diversity in a common greenhouse environment. This work will inform ongoing and future marsh restoration efforts in Belle Isle and the surrounding region.

Using Big Data to Quantify and Cultivate Genius

Targeting adolescent depression symptoms using network-based real-time fMRI neurofeedback and mindfulness meditation

Adolescents experience alarmingly high rates of major depressive disorder (MDD), and these episodes are highly recurrent and increase suicide risk. Recently, the U.S. Surgeon General and leading pediatric health organizations declared a national state of emergency for adolescent mental health, underscoring that the majority of affected adolescents do not receive adequate treatment. As gold-standard depression treatments (antidepressant medications and cognitive behavioral therapy) are effective for only ~50% of adolescents, there is a critical need to develop novel treatments to improve clinical outcomes, particularly those that target core mechanisms fundamental to MDD.  Rumination (i.e., repetitive, negative patterns of thinking typically focused on the self) contributes to MDD onset, maintenance, and recurrence as well as predicts treatment non-response and relapse. Mindfulness meditation has been shown to suppress the default mode network (DMN), a set of brain regions that are overactive in depression and that underlie rumination.   We are launching a large scale, clinical trial to do a mindfulness based real-time fMRI neurofeedback intervention in adolescents with MDD in order to quiet the DMN and mitigate rumination.

Time-locked psychophysics: speeded responses to visual stimuli

The project will use variations on a classic method called response time (RT) measurement, which has human participants respond as quickly as possible to the presentation of carefully-controlled visual patterns.  One goal is to demonstrate that the fastest RTs are triggered by the very early responses in the photoreceptors of the retina of the eye. Two parallel pathways in the visual system called ON and OFF pathways, generate opposite-polarity responses. A second goal is to test the hypothesis that these two pathways can be measured and studied separately using these speeded behavioral responses

CAREER: Sedimentary signatures of large riverine floods to constrain risk and build resiliency

The traditional paradigm in river and floodplain management relies almost exclusively on stream gage measurements as the key dataset informing flood hazard assessments, while largely neglecting the geomorphic dynamics and resulting sedimentary records preserved in floodplains. This project builds on prior work in the development and application of stratigraphic records in floodplains by harnessing recent advances in hydraulic modeling, environmental sensors, and sedimentology to constrain flood hazard assessments. This research is integrated with an education and outreach plan designed to attract, motivate, and train community college students in geoscience research through an established internship program.

Determining how aquaculture grow-out methods can reduce the negative effects of parasites and micropollutants on farmed oysters  

We will be collaborating with local oyster farmers to investigate how growing methods (on the bottom vs. Floating) and water quality affect the prevalence and intensity of common oyster parasites. The knowledge developed through this work will be shared with various stakeholders through workshops and aquaculture professional associations.  

Bioinspired Light-Escalated Chemistry (BioLEC) 

The mission of the BioLEC Energy Frontier Research Center (EFRC) is to combine light harvesting and advances in solar photochemistry to enable more powerful editing, building, and transforming of abundant materials to produce energy-rich feedstock chemicals. As part of the BioLEC EFRC, we will develop new supercharged light-powered catalysts and reactions an deepen our understanding of existing ones, through which valuable products can be generated from plentiful molecules such as those extracted from waste and renewal resources.  

Disease-homing light delivery by engineering bioluminescent immune cells for whole body precision photomedicine 

Photomedicine avoids traditional side effects of systemic chemotherapy, yet effective outcomes are dependent on direct irradiation from an external light source that limits the scope and the types of cancers that may be treated. This proposal develops a precision photomedicine platform that exploits natural disease-homing properties of the immune system to mediate bioluminescence-activated phototherapy in combination with established technology to deliver photoactive therapeutic agents selectively to tumor cells. Successful, proof-of-concept studies will establish a new paradigm of systemic, whole-body phototherapy by enabling immune cell-based light delivery to deep and diffuse metastatic disease that would otherwise be impractical to treat using an external light source, thereby overcoming a major limitation of conventional phototherapy. Photomedicine avoids traditional side effects of systemic chemotherapy, yet effective outcomes are dependent on direct irradiation from an external light source that limits the scope and the types of cancers that may be treated. The proposal develops a precision photomedicine platform that exploits natural disease-homing properties of the immune system to mediate bioluminescence-activated phototherapy in combination with established technology to deliver photoactive therapeutic agents selectively to tumor cells. Successful, proof-of-concept studies will establish a new paradigm of systemic, whole-body phototherapy by enabling immune cell-based light delivery to deep and diffuse metastatic disease that would otherwise be impractical to treat using an external light source, thereby overcoming a major limitation of conventional phototherapy.  

This high-risk, high-reward concept grant will be performed by the Spring Lab at Northeastern University in collaboration with the Schaffer-Nishimura Lab at Cornell University. 

Repurposing Gram-positive Antibiotics for Gram-Negative Bacteria using Antibiotic Adjuvants 

The multidrug-resistant (MDR) sepsis pathogen Acinetobacter baumanni presents an enormous ongoing challenge to public health. Current treatment options for infections with these bacteria are extremely limited. Our research examines a class of small molecules called antibiotic adjuvants that greatly boost the activity of several existing antibiotics against A. baumanniim, with the goal of developing new combination approaches to treat MDR infections.  

PlantSynBio: A Novel CRISPR SynBio Tool for Investigating and Reprogramming the Regulation of Alkaloid Biosynthesis in Catharanthus roseus 

Plants produce a white array of valuable, biologically active natural products we use as medicines. This grant will enable engineering for enhanced drug production from the medical plant, C. roseus.

Identifying factors that promote soft coral resilience in climate change-induced

This work, in collaboration with a biophysicist, will explore the resilience of soft corals to rising ocean temperatures by understanding two main adaptations: the coral microbiota, and the morphology and growth patterns.

Sex-dependent pain processing circuitry in classical Pavlovian fear conditioning

Traumatic experiences create powerful memories by linking information about the trauma itself with environmental cues associated with the event. Our lab has found evidence that males and females may form these memories using different brain regions, and this grant will allow us to probe this question more deeply by recording neural activity in real time as animals are learning.