Oakland University

NSF Awards · FY 2026 · 2026-07

Sulfur is an attractive material for energy storage because it is abundant, inexpensive, and can store more energy than materials used in batteries today. Still, sulfur-based batteries have not reached their full potential. The various forms sulfur takes during operations are not well understood. This project focuses on a newly discovered liquid sulfur phase. This liquid form of sulfur has not been explored even though it may be a transformative energy material. The project will investigate how different sulfur phases form, transform, and interact with electrodes during charging and discharging. The team will design sulfur-based electrochemical cells that deliver high energy density quickly and efficiently. The project will lead to a better understanding of sulfur phases and pave the way for low-cost, high-performance sulfur-based energy storage systems. The project will establish a Microscopy, Spectroscopy, and Electrochemical Characterizations (MSEC) program for OU students and the local automotive industry. This project will provide undergraduate research opportunities in the Engineering Chemistry program, introduce K–12 students and teachers to energy science and engineering concepts, and inspire the next generation of scientists and engineers. Sulfur is a highly promising cathode material due to its abundance, low cost, and exceptionally high theoretical capacity. However, the behavior of sulfur during battery operations — especially its phases and transitions, which govern electrochemical performance — is poorly understood. This project highlights a liquid sulfur phase at room temperature, a newly discovered, largely unexplored, and potentially transformative energy material system. The project comprises four objectives: (1) Understand intermediate sulfur phases using in situ and operando platforms; (2) Chemically generate liquid sulfur on carbon electrodes using redox mediators; (3) Electrochemically generate liquid sulfur on carbon electrodes via fast and pulse charging; and (4) Design liquid-sulfur electrochemical cells with high capacity and fast kinetics. The project will employ in situ and operando platforms that integrate customized electrochemical cells, as well as optical, Raman, X-ray, and electrochemical microscopy and spectroscopy, along with a high-speed camera and microelectrodes. The research will close key knowledge gaps in sulfur phases and transitions, leading to the design of high-performance, low-cost sulfur-based electrochemical systems. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2026 · 2026-06

This project will study deep learning, a class of machine learning algorithms based on deep neural networks (DNNs) that are becoming increasingly popular due to their successful applications in many areas, such as healthcare, transportation, and entertainment. DNN programs, like any other software, may contain faults that might undermine their safety and reliability in mission-critical applications. Software engineering research has produced a rich body of software fault localization techniques; however, they are not immediately applicable to DNNs. This is mainly because traditional software and DNN models are based on fundamentally different computational models, and the definition of “bug” differs in the two kinds of software. The project will improve fault localization for DNNs with novel approaches for monitoring model behavior during the training of the neural networks. DNN models are also used by practitioners who may not be experts in DNN architecture, and fault localization techniques proposed by this project have the potential to make debugging DNN more accessible, improving the safety and quality of AI-based software. Training DNN models is known to be expensive. This project has the potential to reduce training costs by identifying errors early on that can be rectified. This project will explore three novel research directions. (1) Identify dynamic behavior of DNN models that need to be reified in traces. The preliminary work of the investigators has shown that reifying the dynamic behavior of fully connected neural networks (FCNN), such as changes in learnable parameters help with bug localization in FCNN; however, other model architectures like Convolutional Neural Networks (CNNs) have different kinds of learnable parameters. (2) Define novel abstractions of dynamic behaviors in DNN models that will enhance fault localization and repair. This research direction will explore the development of new abstractions that can represent the dynamic behavior of the neural networks succinctly. (3) Reduce the cost of re-training for fault localization by leveraging the abstraction of dynamic behavior. In this direction, the project will create abstractions that not only reduce the training dataset but also enhance the effectiveness of fault localization, thereby saving time and computational resources. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2026-06

Project Summary Proper tube morphology is essential for the function of organs such as the lungs, kidneys, and blood vessels. A key structural feature of these systems is the stable apical extracellular matrix (aECM)—a specialized layer of protein proteoglycans, and lipids secreted by organ-forming cells. This layer lines the luminal (inner) surface of tubes. Stable aECMs, including pulmonary surfactant and mucin-rich coatings, are critical for organ integrity and function, and their disruption is linked to diseases such as pulmonary airway malformations and polycystic kidney disease. In the Drosophila trachea, the stable aECM consists of taenidial folds: spiral, ridge-like structures that line the luminal surface and are functionally similar to aECMs found in mammalian systems. Despite their biological importance, how stable aECMs regulate tube morphogenesis remains poorly understood. Addressing this gap is key to revealing the fundamental mechanisms of tube formation and gaining insight into diseases caused by disrupted aECMs. The objective of this application is to determine how taenidial folds, the stable aECM in the Drosophila trachea, regulate tube morphogenesis during development. We recently identified two Osiris proteins, Osi18 and Osi20, that specifically localize to taenidial folds using antibodies we generated. Using CRISPR, we created Osi18+20 double mutants in which taenidial folds are selectively disrupted. This provides a unique genetic model to investigate how taenidial folds—and more broadly, apical extracellular matrices (aECMs)—regulate tube morphogenesis. Remarkably, these double mutants exhibit early defects in tube morphology, apical actin organization, and mechanotransduction pathway activation—well before tube collapse occurs. These findings indicate that taenidial folds actively regulate tube morphogenesis, beyond their traditional role as structural supports. We hypothesize that taenidial folds drive tube morphogenesis by activating apical mechanotransduction pathways, specifically the Src–Rho–actin remodeling cascade. To test this, we will employ live imaging, immunostaining, genetic interaction analyses, and biochemical assays to define the role of taenidial folds in mechanotransduction and epithelial remodeling. This research will uncover a novel function for stable aECMs as active, instructive regulators of tissue morphogenesis. Given their conserved presence in tubular organs across species, studying how taenidial folds guide epithelial remodeling during Drosophila tracheal development will reveal broadly applicable principles of tubulogenesis. These insights will enhance our understanding of the developmental basis of human diseases affecting the lungs, kidneys, and vasculature. Aligned with the NIH R15 mission, this project will support an undergraduate-centered research program at Oakland University, providing students with hands-on training in developmental biology, genetics, live imaging, and molecular techniques—preparing them for future careers in biomedical research.

NIH Research Projects · FY 2026 · 2026-03

PROJECT SUMMARY Autophagy is an evolutionarily conserved catabolic process necessary for cellular homeostasis. Dysfunction in autophagy is linked to aging and many human pathologies, including neurodegeneration, cardiovascular diseases, and immune disorders. Cells utilize autophagy to degrade and recycle cellular components, aged or misfolded proteins, and defective organelles. Cargo targeted for autophagic degradation is delivered by autophagosomes to the vacuole in yeast and plants or to lysosomes in mammalian cells. While this process is active at a basal level, it is significantly induced during stress, such as amino acid and nitrogen limitations. In addition, autophagy machinery is also utilized to degrade specific cargo such as ribosomes via ribophagy, or mitochondria via mitophagy. During starvation stress, the cell downregulates many genes, enhancing the expression of the genes critical for mounting a survival response. This includes increased expression of autophagy-related (ATG) genes. Dynamic changes to chromatin structure are critical for modulating gene expression. These changes are mediated by chromatin-associated factors such as histone modifiers, chromatin remodelers and histone chaperones. RSC (Remodels the Structure of Chromatin) is an ATP- dependent chromatin remodeling complex conserved from yeast to humans. Likewise, the FACT complex (Spt16/Pob3 or Spt16/SSRP1) is essential for maintaining chromatin structure. Induction of autophagy during starvation leads to degradation of proteins and organelles to resupply key nutrients for survival. Prolonged starvation is likely to severely deplete cellular protein levels, including those required for genomic integrity. However, how the cell maintains its chromatin structure and its ability to recover from chronic stress remains poorly understood. In this proposal, we will use Saccharomyces cerevisiae as a model organism to understand how cells recover from chronic stress, and the importance of chromatin factors, RSC and FACT in this process. In the specific aim 1, we will characterize changes in chromatin structure, transcription, and histone modifications during extended starvation, and determine the role of FACT and RSC in the recovery from stress. In specific aim 2, we will examine how RSC depletion affects ribophagy, and identify factors that promote this process in an RSC-dependent manner. These studies will be valuable in understanding chromatin factors' role in cell survival during prolonged stress.

NSF Awards · FY 2025 · 2025-10

The rapid development of GPU hardware has promoted scientific supercomputing, enabling exascale data production on heterogeneous supercomputing systems. With GPU dominance in heterogeneous computing, the cyberinfrastructure of GPU-based scientific data compressors is still maturing, and several gaps need to be addressed: existing frameworks lack adaptations to many scientific data analysis requirements; there are no user-friendly interfaces and off-the-shelf solutions for GPU-based scientific data compressors; and the compressors that support non-NVIDIA GPU architectures are very limited. This project develops a user-friendly, high-performance, and portable GPU-accelerated data reduction cyberinfrastructure for all primary GPU-equipped supercomputing systems. It will mitigate data challenges on GPU-equipped supercomputing systems, improve data analysis efficiency, and eventually accelerate scientific discovery. This project will continuously contribute to the education and training of graduate students by enhancing the quality of computing-related curricula in heterogeneous scientific computing, data management, and visualization. This project builds Scientific GPU Compression Cyberinfrastructure (SGCC), a user-friendly end-to-end cyberinfrastructure of GPU-based data compression for scientific data workflows, by porting, extending, and optimizing multiple existing capabilities, including but not limited to: the cuSZ family of error-bounded lossy compressors, GPU-based lossless encoders, QCAT (a CPU-based compression quality assessment toolkit), the Kokkos ecosystem (a multi-backend performance-portability framework), LibPressio (the unified programming interface of scientific compressors), and HDF5. To create SGCC, the project combines three thrusts: (1) SGCC ensures its efficiency and effectiveness in practical scientific data analysis workflows, providing adequate support for diverse data formats and compression quality targets; (2) SGCC improves the usability of the GPU-accelerated data-reduction ecosystem by providing high-level language bindings, command line interface, and user-interface integrated with visualization functionality; and (3) SGCC enables state-of-the-art GPU-accelerated scientific data compressors on multiple heterogeneous computing platforms, such as NVIDIA, AMD, and Intel. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY The project aims to improve our understanding of the role of a novel RNA Binding Motif Protein 48 (RBM48) and its impact on cell proliferation and differentiation. RBM48 represents a core minor spliceosomal protein essential for the splicing of minor or U12-type introns, constituting a small fraction of deeply conserved introns. The splicing of U12 introns has a similar role in cell differentiation across divergent eukaryotes. However, the mechanism by which U12 splicing controls these cell differentiation pathways is poorly understood. Our prior work demonstrated that the disruption of orthologous RBM48 in humans and plants disrupts the splicing of multiple minor intron-containing genes (MIGs). The aberrant splicing of U12 introns in human hematopoietic stem and progenitor cells (HSPCs) adversely impacts normal myeloid cell differentiation, which is proposed to be associated with myelodysplastic syndrome and subsequent onset of acute myeloid leukemia. Human RBM48 encodes multiple transcript isoforms by alternative splicing; however, the biological relevance of this process and the role of transcript isoforms is unclear. The proposal aims to implement cellular, genetic, genomic, and bioinformatic tools to investigate the mechanistic role of RBM48 and its transcript isoforms in U12 splicing. The proposal will also examine how RBM48 modulates U12 splicing in HSPCs, directly affecting differentiation, engraftment potential, and self-renewal of this stem cell population. The data generated will no doubt bridge the gap in our understanding of a growing number of diseases ranging from hematological and neurological to cancer that have been linked to defects in U12 splicing. In Specific Aim 1, we will use a developed genetic assay in human K562 leukemia cells to determine the functional role of RBM48 transcript isoforms in U12 splicing and implement mRNA-seq-based transcriptomic data to determine impacted genes and downstream processes that regulate U12 splicing mediated cellular differentiation. In vivo and in vitro protein-protein interactions of RBM48 transcript isoforms will be used to elucidate the mechanistic role in U12 splicing. The data will lead to a better definition of U12 intron consensus and potentially identify sequence targets of RBM48. We have shown that RBM48 knockdown alters the survival and proliferation characteristics of K562 cells. In Specific Aim 2, we will use an RBM48 knockdown strategy in HSPCs to demonstrate its essential role in U12 splicing mediated impact on differentiation, cell fate determination, and self-renewal potential. We will use a combination of phenotypic and in vivo and in vitro functional assays to accomplish these outcomes. By completing the proposed study, our long-term goal is to enhance our understanding of how U12 splicing regulates cellular differentiation, which will enable us to identify new drug targets and lead to robust treatment strategies for patients suffering from a growing number of diseases attributed to aberrant splicing of U12 introns.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY/ABSTRACT The balance between cell death and survival is a critical factor for maintaining human health. Cells must rapidly adapt to stress conditions within their environment to survive. Cytoprotective measures require the cell to process stimuli, and often, alter gene expression within regulatory circuits. The ability to design and build synthetic cells for innovative biomedical applications requires a complete understanding of how critical cellular pathways are regulated. However, a comprehensive model for how a single cell functions has remained elusive. This gap in knowledge is a major barrier to developing synthetic cells for biomedical purposes. Thus, there is an urgent need to elucidate molecular mechanisms required for cell survival. Macroautophagy/autophagy is an essential mechanism that preserves cell health under homeostatic conditions and supports survival under stress. Autophagy is a dynamic pathway of cellular degradation and recycling that is conserved from yeast to humans. Basal autophagy is low, but is markedly upregulated during stressful conditions. At present, >40 autophagy- related (ATG) genes have been identified in yeast; many of these genes are conserved in humans. This complexity requires the cell to maintain precise control over autophagy at multiple regulatory levels. Despite this need for strict regulation, much remains unknown about how autophagy is fine-tuned in the cell. In humans, perturbation of autophagy can have deleterious effects on cell health and survival, contributing to disease pathogenesis. In fact, aberrant autophagy is associated with diverse human pathologies such as neurodegeneration, cancer, and lysosomal storage and metabolic disorders. The rationale for this project is that there is a gap in our understanding of the molecular mechanisms driving responses necessary for cell survival under stress conditions. Our objective is to determine the role(s) of Pseudouridine synthases (Pus7 and Pus4) in nonselective and selective autophagy. Pus enzymes catalyze the RNA-independent isomerization of uridine to pseudouridine (Ψ). Our hypothesis has been developed based on preliminary data that was generated using the budding yeast model system. The yeast system provides numerous advantages, including the ability to perform biochemical and molecular genetic experiments quickly and easily, and in ways that are suitable to actively engage undergraduate students in authentic biomedical research. Since autophagy is highly conserved from yeast to humans, we expect that our findings from this project can be applied to furthering our understanding of cell survival in humans. This project will increase the participation of undergraduates in a rewarding biomedical research experience at Oakland University, which is in the Detroit metro area. This project is innovative because it provides insight into the mechanistic role(s) of Pus7 and Pus4 in cell responses to stress and uses innovative approaches to do so. The proposed work is significant because it advances our knowledge of the physiological roles of Pus enzymes in cells and how cells dynamically respond to environmental stress. This project will generate fundamental knowledge required for understanding cell survival mechanisms under stress conditions.

NSF Awards · FY 2025 · 2025-09

Under this three-year RET Site: More than Automotive–Toward a Healthier, Sustainable Society (MATHS2) ten participants each year will engage in engineering research featuring the automotive industry and translate their experiences into creative curricula for their students. Teacher participants will engage in cutting-edge research in areas intersecting engineering, health care and sustainability. A special focus is the concept of ‘What is an engineer?’ where participants will examine different areas of engineering and the impact of engineering in society and potential careers. This site is structured around a thoughtful coupling of both state-of-the-art engineering research experience with research-driven educational coaching on how to translate these experiences into K-12 classroom curricula. Two key outcomes of this program include an interactive, online repository of the curricular elements developed through the program and an annual workshop geared toward area teachers to enhance engagement in STEM instruction. The MATHS2 RET Site, located in the metro-Detroit area, attempts to shift the local vernacular on ‘What is an engineer?’ from an automotive stereotype to a broader portrait of problem solvers that tackle society’s most pressing issues. This shift in perspective can translate to broader K12 student participation in STEM educational and career pathways, particularly in the metro-Detroit area, as well as supporting student learning aligned with engineering education strands. Collaborative research experiences between teacher participants and faculty mentors span several interdisciplinary fields that range from optimizing algae as a feedstock for biodiesel production to developing socially assistive robots for healthcare. Weekly cohort workshops will develop course materials and curricula with education faculty. Regular workshops and seminars to deepen teachers’ engineering knowledge and strengthen their pedagogical strategies. Pragmatic follow-up plans include 2 site visits to the RET teachers’ classrooms, an annual K-12 teacher training workshop on phenomenon-driven and inquiry-oriented learning and development of an interactive online repository of the curricular elements developed through the program. The key outcomes of this RET site are to help quantify the extent to which non-automotive engineering applications increase participation and efficacy in STEM for students. In addition, the classroom lessons or units will be disseminated through an annual teacher workshop as well as an online, interactive repository (Teach Engineering). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-08

Hemostasis is a constant balancing act between pro- and anticoagulant factors, platelets, and the vasculature that is required to prevent excessive bleeding or pathological clotting. The anticoagulant, Tissue Factor Pathway Inhibitor (TFPI), is a vital factor in this balance and modulates a broad range of bleeding and clotting disorders through inhibition of TF-FVlla, FXa, and prothrombinase (FXa-FVa). The TFPI gene is evolutionarily conserved and due to alternative splicing, different TFPI isoforms are predominant within distinct pools. While the specific inhibitory function of each TFPI isoform has been characterized, little is known regarding differences in isoform-specific contributions under prothrombotic disease conditions such as Factor V Leiden (FVL) and during embryonic development. Further, the pre-mRNA splicing and processing mechanisms dictating expression of each isoform are unknown. As a causal relationship exists between aberrant splicing of FV and TFPI isoform-specific function in human bleeding disorders, these mechanisms, coordinated by precise cues directed at maintaining the hemostatic balance, are highly relevant. Thus, the long-term objective of this proposal is to differentiate the physiological, site-specific production of each TFPI isoform at a molecular level and define their anticoagulant function in embryonic development and disease. TFPla is the only isoform present in platelets and the only isoform that inhibits prothrombinase during the initiation of blood coagulation. Additionally, global TFPI deficiency results in prothrombotic perinatal lethality in FVL mice, and TFPla prothrombinase inhibitory activity is reduced in the presence of FVL. To this end, K99 phase studies revealed that TFPla and its inhibition of FVL-containing prothrombinase play an important role in placental angiogenesis and embryonic survival and further characterized the biological activity of new platelet-specific TFPla splice variants identified in mice and humans. The R00 phase studies will leverage the evolutionary conservation of alternative TFPI splice forms and splicing signals embedded in highly conserved sequences to determine cisRNA element and trans-acting splicing factor interactions regulating TFPI isoform diversity in mice and humans. Deciphering the pre-mRNA processing mechanisms that regulate site-specific TFPI isoform expression will delineate how alternative splicing contributes to the physiological and pathophysiological hemostatic balance during embryonic development and in adulthood. As there are many patients with bleeding and clotting disorders of unknown cause, the relation of aberrant splicing to these diseases represents a relatively new and unexplored area with great potential for launching a successful independent career. This work will establish an innovative research program at the intersection of RNA biology and coagulation, enabling the Pl to lead a uniquely interdisciplinary investigation into how splicing regulation influences platelet function and thrombotic risk. The R00 phase will provide the foundation for future R01-level studies and sustained contributions to the fields of thrombosis and hemostasis and RNA regulation.

NSF Awards · FY 2025 · 2025-08

The National AI Research Resource (NAIRR) provides U.S.-based researchers with high-performance computing, data, and AI tools, fostering broad access to cutting-edge AI research. Training scientific researchers to fully utilize NAIRR capabilities is critical in advancing the nation’s science and technology. This project, a collaboration between Oakland University and Worcester Polytechnic Institute, aims to increase awareness and promote broader adoption of the NAIRR Pilot. The project will organize two 12-workshop series over two years, offering hands-on training for emerging researchers to utilize NAIRR for using AI in three critical domains: AI for Cybersecurity & Trustworthy AI, Edge AI, and Autonomous Driving. These workshops will provide guidance on integrating NAIRR’s computational resources, datasets, and AI frameworks in the R&D efforts to develop secure, efficient, and impactful AI use cases in these three domains. It will equip researchers with the knowledge and tools to develop secure and innovative AI systems, fostering advancements in cybersecurity, autonomous systems, and other interdisciplinary AI applications. The NAIRR resource utilization training will guide participants in using NAIRR resources to further research and prepare students for projected future workforce needs. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-07

Project Summary PTEN is classically considered a lipid phosphatase. Hence, loss of PTEN perpetuates the PI3K-Akt signaling to promote cell proliferation, causing pre-clinical dysplasia or tumor. On the other hand, emerging evidence suggests that PTEN has a protein phosphatase activity to regulate the phosphorylation at Ubiquitin protein. In this project, we suggest that PTEN regulates the ubiquitination of Snail/Slug transcription repressor proteins and the autophagy pathway in intestinal epithelial cells (IECs). PTEN deficiency elevates the ubiquitination of Snail/Slug. By lowering YKT6, PTEN deficiency also suppresses autophagosome-lysosome fusion to inhibit autolysosome formation. Then, aborted autolysosomes cannot degrade ubiquitinated Snail/Slug, leading to augmented Snail/Slug repressors. Consequently, it represses the cell-junction protein expression, disrupting the cell-cell junction and segregating the IEC from the intestinal epithelium. Regarding the role of PTEN in tumorigenesis, previous studies suggest that loss of PTEN gene alone cannot cause tumor development in the intestine. Indeed, IEC-target Pten knockout (KO) (PtenΔIEC/ΔIEC) mice do not develop tumors in the intestine. However, we observed that PtenΔIEC/ΔIEC mice have enhanced cell growth and pre-clinical dysplasia in the intestine. Human colon cancer tissues have reduced expression of PTEN and MYD88 (a key immune regulator) compared to normal tissues. Accordingly, PtenΔIEC/ΔIEC mice develop massive intestinal tumors and metastasis when combined with Myd88-KO. Therefore, our overall hypothesis is that (1) PTEN deficiency can induce pre- clinical dysplasia, but an immune surveillance mechanism restrains its tumorigenic potential in the intestine. (2) If an immune mechanism is compromised, it unleashes the tumorigenic potential of the PTEN deficiency. In parallel, (3) PTEN deficiency can disrupt the cell-cell junction, allowing the segregation of dysplastic cells from the epithelium. Further, a segregated dysplastic cell migrates to an extra-intestinal organ, developing tumor metastasis. Based on the hypothesis, this R15 application proposes two major research aims: Aim 1 investigates the non-classical function of PTEN in IECs. Aim 2 tests a potential intervention to prevent PTEN-promoted tumorigenesis and metastasis.

NSF Awards · FY 2025 · 2025-05

This NSF project aims to advance the national prosperity and welfare with enhanced sustainable electrification systems. The project will bring transformative change to the repurposing process of retired electric vehicle batteries with reduced instrumentation cost and shortened testing time. This will be achieved by the development of a novel estimation and monitoring framework that requires fewer sensors for each cell string. The intellectual merits of the project include the development of a sensor-lean and computation-efficient estimation and monitoring framework for large distributed systems, with a specific focus on second life electric vehicle batteries to reduce the repurposing cost and to maximize their lifespan. The broader impacts of the project include environment improvement with less emissions, enhancements to undergraduate and graduate degree programs for STEM workforce development, and inclusion of undergraduate students in electric vehicle racing competition. Existing approaches on battery cell parameter and state estimation generally require extensive testing of each individual cell, which may not scale up for the large number of retired electric vehicle batteries. To address this, this project will develop a transformative estimation and monitoring framework for second life electric vehicle batteries. Four closely integrated research objectives are planned: (1) Develop a novel dense extended Kalman filter to simultaneously estimate parameters for a large number of connected cells during the repurposing process, without requiring sensor measurements for each cell individually; (2) Develop an online sensor-lean behavior monitoring scheme based on temporal logic to extend the battery lifespan in second life applications; (3) Develop a stochastic hybrid filtering approach with novel model condensing to enable real-time cell level monitoring with limited sensor measurements; and (4) Evaluate and validate the proposed framework on a residential wind energy generation system. Collectively, advances from these research endeavors are expected to make second life electric vehicle batteries and more affordable and more durable, and will create new computationally-efficiency estimation mechanism for large distributed systems with limited sensing capability. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-03

Cell growth is closely linked to cell division; to meet the demands of growth, cells must increase protein synthesis. The synthesis of new ribosomes (which make proteins) plays a crucial role in supporting the increased protein synthesis required during the cell cycle and division to make new cells. However, the role of the synthesis of new ribosomes in cells that are fully matured and incapable of cell division remains much less clear. Mature skeletal muscle cells are differentiated cells, meaning that they cannot undergo cell division anymore; yet several proteins typically associated with the cell cycle are expressed in skeletal muscle cells, even though they will never divide. This research project will investigate the roles of proteins responsible for cell cycle progression in non-dividing cells, such as mature muscle cells, in particular the synthesis of new ribosomes. Using novel genetically modified mouse models, the researchers will manipulate the cell cycle to explore the effects slowing or speeding up the cell cycle on ribosome production and muscle cell size. Undergraduate students working from the Principal Investigator’s lab, and from a new Course-Based Undergraduate Research Experience (CURE), will receive extensive training on muscle biology while supporting this project. While cell cycle progression has been extensively studied in proliferative cells, the role of cell cycle regulators in postmitotic cells remains unclear. Fully differentiated skeletal muscle cells can express several cell cycle regulators that are key to ribosome biogenesis – a cellular process where we hypothesize that the role of these regulators is conserved in postmitotic cells. This research aims to investigate the role of cell cycle regulators in mature skeletal muscle cells, focusing primarily at the level of the Cyclin-Dependent Kinase 4 (CDK4), a central kinase regulating ribosome biogenesis in proliferative cells. Specifically, this study will: 1) Determine whether CDK4 regulates muscle ribosome biogenesis and muscle cell size, and; 2) Test whether promoting cell cycle progression via a constitutively active CDK4 in differentiated muscle cells causes the muscle progenitor cells, known as satellite cells, to fuse with the mature myofibers. To address these questions, the PI, graduate, and undergraduate researchers will use genetically modified mouse models to specifically and conditionally knock out or overexpress key regulators of the cell cycle, such as CDK4, in mature myonuclei. If the hypothesis is correct, the results from this proposal will represent a paradigm shift in our understanding of the role of cell cycle in terminally differentiated cells, such as muscle cells. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-01

NON-TECHNICAL SUMMARY Sodium, similar to lithium, can be used as the electrode material in rechargeable batteries. Sodium is 1,000 times more abundant than lithium, potentially lowering battery costs. Due to its strong reactivity, sodium forms a corrosion film on the surface during battery operation, significantly impacting the performance of batteries. However, the composition and evolution of this corrosion film remain largely unknown. This project, supported by a LEAPS-MPS award, advances our understanding of this corrosion film and lays a firm foundation for developing next-generation sodium-based rechargeable batteries. The project outcomes will broadly impact clean energy technologies and enable a world with zero-carbon emissions. The educational outreach targets diverse engagement, focusing on female and underrepresented students in STEM fields. The activities include integrating research into the curriculum and electrification certificate programs, hosting undergraduate research in the lab, and engaging K-12 students in electrochemistry, especially Girls in Science and Engineering and minority students. The educational plan educates students at all levels about research areas at the intersection of materials, electrochemistry, microscopy, and spectroscopy. TECHNICAL SUMMARY Sodium (Na) is a compelling anode material due to its low electrochemical potential, high specific capacity, and natural abundance. Due to its strong reducing property, Na forms a corrosion film – solid electrolyte interphase (SEI) on the surface, impacting battery performances such as cyclability, capacity retention, rate capability, and safety. The understanding of the SEI is challenged by its complex composition, dependence on electrolyte and temperature, thin thickness (several to tens of nanometers), sensitivity to ambient conditions, and its constant evolution in a closed system. This fundamental research project, supported by a LEAPS-MPS award, elucidates the composition and evolution of Na SEI by using in-situ and non-invasive Raman spectroscopy enhanced by Na metal nanostructures, bridging interdisciplinary fields of electrochemistry and nanophotonics. Specifically, researchers at Oakland University focus on (1) probing Na SEI as a function of electrolytes using a Na Moiré metasurface and (2) in situ probing Na SEI using Na metal microparticles and nanoparticles. The technical approaches for the research include plasmonic Na metasurfaces for surface-enhanced Raman spectroscopy (SERS), a microelectrodes-based Na particle synthesis and characterization platform, and in situ and operando Raman spectroscopy coupled with a temperature stage. The expected outcomes of this project will advance the fundamental knowledge of Na SEI, providing insights into crucial SEI-electrolyte and SEI-temperature relationships. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-11

The mission of the Center for Industrial Metal Forming (CIMF), which is comprised of Ohio State University (OSU), Oakland University (OU), and University of New Hampshire (UNH), is to perform cutting-edge, pre-competitive fundamental research in metal forming science and engineering. Metal forming processes are widely used in automotive, aerospace, defense, electronics, appliances, and biomedical industries and play an essential role in generating significant economic impact and attaining global market competitiveness. Transportation, defense, aerospace, household and biomedical industries consume and process large quantities of metals in forgings, extrusions, and sheet metal components. New and future demands in metal forming will require new material processing methods, innovative tool designs, new lubricants, automation, AI, integration with computing resources, and intelligent sensors to improve quality, minimize variability, and reduce the amount of scrap for lightweight and high strength materials. Significant needs and challenges exist with respect to computational and materials modeling, developing innovative forming processes using state-of-the-art technologies, and creating equipment and die innovations to enhance the forming of metals. If addressed, these advancements would lead to considerable product performance, manufacturing, and societal benefits. CIMF activities will strengthen the US manufacturing industry and facilitate rapid development of new metal forming technologies by conducting industrially-relevant and challenging projects that couple fundamental and applied research. CIMF will collaborate closely with its industrial Members to prepare work-ready professionals for the metal forming industry through academic programs and industrial training to improve the knowledge and skill base for these critical industries. Advancement in material utilization and broader implementation of lightweighting alloys from CIMF research will help to protect the environment from CO2 emissions. Diversity with respect to underrepresented groups in CIMF research and educational efforts will be achieved through proven programs and outreach activities. OSU will focus on material suppliers and automotive industries, due to the concentration of companies in these areas in the Midwest U.S. CIMF will drive innovation and competitiveness in U.S. industry by conducting transformational research in novel forming processes, Integrated Computational Metal Forming, advanced equipment and die technologies, the application of sensors and the Industrial Internet of Things (IIoT) in metal forming, and artificial intelligence (AI)-assisted materials modeling. This will necessitate an interdisciplinary approach with experts from manufacturing engineering, electrical engineering, materials science, computational methods, AI and data analytics, and experimental mechanics. The industrial Members of CIMF include original equipment manufacturers, components suppliers, material suppliers, and machine builders. Vertical, fundamental advances will be achieved by employing innovative approaches in sheet metal/tube forming, forging, and extrusion, improving material formability, advancing methods for virtual process design and simulation, and employing new lubricants and metal forming equipment. Specifically, projects target process innovation, forming control based on IIoT, energy-efficient forming machines, etc. The results will be advancements in material utilization and weight reduction, final part performance, industry-friendly computational tools for process design, metal forming dies with extended life, and industrial metal forming processes of increased productivity, across a range of advanced material systems. OU has unique facilities and research expertise with respect to high volume stamping processes, including die materials, lubricants, sensors, and numerical simulations. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-10

This three-year renewal REU Site: Applied Research Experience in Electrical and Computer Engineering (ApREECE) program is hosted by Oakland University. Ten undergraduate students each year will have opportunities to investigate selected cutting-edge areas of electrical and computer engineering research embedded in solving current real-world challenges. REU students will engage in projects in bioengineering, GPU computing, embedded computing, machine learning, artificial intelligence, autonomous driving, power systems, and controls. Students will work in groups of two on five separate projects, allowing for a close and personal interaction with the faculty for each project. Professional development activities and field trips are planned to a local conference, competition, and R&D facility. The SAE Young Automotive Professionals Conference and the annual Intelligent Ground Vehicle Competition (IGVC) are expected to overlap the ApREECE program. Participants will learn about the possibilities and the impact of engineering on our lives through close interaction with faculty, research staff, and our industry collaborators in the Metro Detroit Area. Providing undergraduates with an opportunity to function as researchers on projects that are current, relevant, and interesting can have profound positive influences to pursue STEM careers. With close mentoring from faculty, the students will gain valuable skills in contributing to successful research, teamwork, communication, and dissemination of their work through technical conferences. Students will produce project write-ups and an “innovation plan” and present their work at two conferences. The plan will consist of a problem statement, research performed, preliminary results, and an outline of ways their discoveries can be used to innovate/enhance existing products or solve current problems. These plans will be presented for feedback to a review panel consisting of experts of various backgrounds. The first internal mini-conference is open to the public. The second conference is an annual undergraduate research conference held at Michigan State University. Finally, write-ups will be submitted to appropriate professional conferences and authors of accepted papers will be invited and funded to travel with their advisors to present their work. This Site is supported in part by funds provided to the National Science Foundation by the Semiconductor Research Corporation. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-10

This project will contribute to the national need for well-educated scientists, mathematicians, engineers, and technicians by supporting the retention and graduation of high-achieving, low-income students with demonstrated financial need at a consortium of six academic institutions in Alabama and Michigan: Tuskegee University, Auburn University, Auburn University Montgomery, Oakland University, Southern Union State Community College, and Troy University. This institutional consortium represents a HBCU, private and public 4-year institutions, a 2-year community college, two predominantly undergraduate institutions, and three doctoral-granting institutions. Over its 5-year duration, this Track 3 Collaborative project will fund scholarships to 72 unique full-time students who are pursuing associate’s, bachelor’s, and master’s degrees associated with Sciences (Physics, Chemistry, Mathematical, Computer) and Engineering (Materials, Mechanical, Software, Electrical, Computer). First-year students will receive up to four years of scholarship support, while transfer and graduate students will receive up to two years of scholarship support. The project aims to increase student persistence in STEM and promote their workforce readiness by linking scholarships with supporting activities, including mentoring, research experiences, graduate school preparation, participation in conferences, professional advising, career planning, and hands-on experience with cutting-edge technologies. Project activities will synergize to promote students’ sense of belonging in the college environment and help them identify as future STEM professionals in high-demand fields. The partnership institutions serve a large number of students from underrepresented racial, ethnic, and economic minorities; thus, this project has the potential to broaden participation in STEM areas of critical need, and advance understanding of how the proposed activities foster academic and professional success in this student population. The overall goal of this project is to increase STEM degree completion of low-income, high-achieving undergraduates with demonstrated financial need. The specific aims are to increase students’ academic skills for college success and professional skills for STEM careers in critical need areas and investigate the impact of its activities on retention and graduation of low-income students. This project will analyze the institutional and personal factors that foster sense of belonging in low-, mid-, and high-income students, and fill a gap in the knowledge base by investigating sense of belonging in connection to a salient professional identity. The project will analyze the support needs of low-, mid-, and high-income students, the extent to which academic advisors’ and professors’ views of student needs coincide with students’ perceived needs, and the role of personal relationships on preventing isolation and strengthening professional identity. A rigorous mixed-methods evaluation will determine the extent to which the project is achieving its goals by assessing student participation in project activities, perceived gains, persistence in the major, and professional outcomes. Results of this project will be disseminated through a website, digital newsletters, data briefs, explainer videos, presentations, and journal publications. This project is funded by NSF’s Scholarships in Science, Technology, Engineering, and Mathematics program, which seeks to increase the number of low-income academically talented students with demonstrated financial need who earn degrees in STEM fields. It also aims to improve the education of future STEM workers, and to generate knowledge about academic success, retention, transfer, graduation, and academic-to-career pathways of low-income students. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-09

Summary G-coupled protein receptor-31 and 39 (GPR31/GPR39) are specific receptors for 12/15-Lipoxygenase (12/15- LO) metabolites; 12- and 15-HETEs respectively. The role of GPR31/GPR39 in the pathogenesis of diabetic retinopathy (DR) has not yet been investigated. Our previous studies demonstrated that diabetes induces upregulation of retinal 12/15-LO and its metabolites, 12- and 15-HETEs, in human and experimental mice. Furthermore, 12/15-LO blockade preserved the blood-retinal barrier in diabetic mice and reduced retinal neovascularization in oxygen-induced retinopathy. Treatment of Müller cells (MCs) with 12/15-LO metabolites induced inflammatory cytokines and upregulated VEGF. However, there is still a critical gap in understanding the mechanism by which 12/15-LO metabolites activate retinal endothelial (RECs) and MCs. Our objective is to determine whether GPR31/GPR39 are involved in the pro-inflammatory and -angiogenic effects of 12/15-LO metabolites in RECs and MCs that lead to vascular dysfunction in DR. Our preliminary data demonstrated expression of GPR31/GPR39 in RECs and MCs and both receptors are upregulated in the retinas of diabetic mice. The transmembrane helices of the GPR31 and GPR39 proteins can be superimposed and 12- HETE bound to the cognate GPR31 receptor and GPR39 on the extracellular side of the proteins. Similarly, 15- HETE binds to GPR39 and GPR31. We will test the hypothesis that in RECs and MCs, GPR31 and GPR39 contribute to activation of signaling pathways that lead to vascular dysfunction in DR. We will test this hypothesis through two specific aims: Aim1: Determine the affinities and relative substrate specificities of GPR31 and GPR39 for 12- and 15-HETEs in RECs and MCs under normal and hyperglycemic conditions. Aim 2: Examine the effects of GPR31 or GPR39 gain-loss-of-function on RECS and MCs under normal or hyper-glycemic conditions. For this purpose, recombinant GPR31/GPR39 receptors will be expressed and purified and the interactions between the receptors and the HETEs will be examined by biolayer interferometry (BLI) and isothermal titration calorimetry (ITC). Affinity and selectivity of the GPR receptors will be tested against synthetic macrocyclic receptors for HETEs. We will test the formation of GPR-HETE complexes in human retinal endothelial cells (HRECs) and rat MCs under both normal glucose (NG), high glucose (HG) compared to osmotic control (OC). We predict increased GPR-HETE complexes by HG treatment. We will determine the effect of GPR31/GPR39 overexpression or inhibition on HRECs' barrier function, migration and tube formation under NG, HG, 12-HETE or 15-HETE conditions. Similarly, effect of GPR31/GPR39 gain-loss-of-function on MCs' viability, inflammatory response and levels of VEGF, and oxidative stress will be assessed. We predict that inhibition of GPR31 and/or GPR39 will improve HRECs barrier function and ameliorate inflammatory, oxidative, and VEGF pathways in MCs under HG or HETEs treatment. Successful completion of this R21 will establish GPR31/GPR39 as potential therapeutic targets to ameliorate vascular damage in DR.

NIH Research Projects · FY 2024 · 2024-09

Project Summary/Abstract Skeletal muscle mass loss during cancer cachexia is one of the most important predictors of poor prognosis and mortality among cancer patients. However, the role played by skeletal muscle mass in the survival of cancer patients has been understood as a mere symptom of poor overall body health. Contrary to this notion, recent studies have demonstrated that skeletal muscle has an independent and active role in improving survival among cancer patients. Proof-of-principle investigations have shown that promoting skeletal muscle mass, for instance by blocking myostatin signaling, can increase lifespan in tumor-bearing mice independently of any effect of the drug on tumor volume. Therefore, understanding the mechanism regulating muscle size can lead to better therapeutic targets to improve health outcomes among advanced cancer patients. Ribosome biogenesis, the de novo synthesis of ribosomes, is a key process determining protein synthesis in skeletal muscle. While there has been great attention recently to the roles of muscle ribosome biogenesis in regulating muscle hypertrophy, the roles of muscle ribosome biogenesis to maintain muscle mass and during muscle atrophy are largely unknown. We have generated a mouse strain in which we can lower ribosome biogenesis specifically and conditionally in skeletal muscle. We crossed the Upstream Binding Factor (UBF, a key transcriptional factor important for ribosomal DNA transcriptional) floxed mouse to the muscle specific human α-skeletal actin (HSA) promoter linked to a CRE recombinase (HSA-MCM). Using this mouse model to reduce UBF levels in adult muscles only (which we termed UBF mKO), we showed impairing muscle ribosome biogenesis causes muscle atrophy particularly in type IIb and IIx myofibers, while Type I and IIa fibers are not affected. Unexpectedly, long-term experiments using the UBF mKO mice demonstrated that impaired muscle ribosome biogenesis have severe consequences to muscle and whole-body metabolism that phenocopied cancer cachexia, including high respiratory exchange ratio (RER) and depletion of adipose tissue. With our reversed engineered mouse model, we were able to recreate cancer cachexia from within muscle, challenging the assumption that skeletal muscle wasting in cancer cachexia is a mere effect of systemic disease. Rather, our preliminary data strongly suggest that cachexia in the whole body can be initiated in skeletal muscle. This proposal seeks to investigate the mechanism of muscle wasting via skeletal muscle and to identify the mechanism leading to overall cachectic phenotype. If our hypothesis is correct, this will be the first evidence that muscle wasting in cachexia can be recreated from within the muscle tissue and that muscle ribosome biogenesis could be a target to mitigate or even abolish cancer cachexia altogether.

NIH Research Projects · FY 2024 · 2024-09

PROJECT SUMMARY Thrombosis is the major underlying pathology that causes many cardiovascular diseases including stroke, ischemic heart disease, and venous thromboembolism (VTE). VTE, which includes both deep vein throm- bosis (DVT) and pulmonary embolism, is the third most common cause of death in the world, to coronary heart disease and ischemic stroke and is responsible for more than 500,000 deaths in the US each year. Imaging methods to diagnose VTE include compression ultrasonography, computed tomography pulmonary angiography (CTPA), or ventilation-perfusion lung scanning. However, each of these imaging methods are qualitative and do not offer a method to determine the type or age of the thrombus, only visualize its presence or absence. Treatment for these conditions varies depending on the thrombus type; therefore, the development of non-invasive diagnostic tools to characterize clot microstructure is critical to the selection of proper treatment and clinical pathways. Photoacoustic imaging, which relies on the acoustic response from tissue after the absorption of pulsed light, is a promising method to both visualize and characterize thrombi. The photoacoustic signal depends on the optical absorption properties of the imaged tissue which vary across wavelengths of light, but exist- ing methods rely on either a single optical wavelength or on differences between the clot and surrounding blood and do not attempt to fully characterize the clot or understand the underlying microstructure. We hypothesize that there is rich acoustic and optical information present within blood clots that can be ex- tracted and quantified using photoacoustic imaging. Therefore, driven by a team of primarily undergrad- uate researchers, we will characterize the unique optical properties of biological chromophores relevant in thrombus formation (Aim 1) and develop algorithms to quantitatively measure blood clot composition in photoacoustic imaging (Aim 2). These studies will establish a foundation for quantitative photoacoustic characterization of thrombosis and develop quantitative monitoring tools to non-invasively diagnose and track thrombus composition over time. With these tools, we envision improved, targeted therapies resulting in faster treatment and improved patient outcomes. Furthermore, this project will have a significant impact on the undergraduate research landscape at Oakland University, supporting the involvement of at least five undergraduate researchers over the project’s duration.

NIH Research Projects · FY 2024 · 2024-09

Project Summary/Abstract Over 2 million people in the United States who have intellectual and developmental disabilities (IDD) engage in some form of problem behavior such as self-injury and aggression. Problem behavior is a major cause of suffering for these individuals and their caregivers, and adversely impacts society as a whole. Problem behavior increases caregivers' burden and strains healthcare and other service systems, as individuals who engage in problem behavior can require prolonged separation from caregivers and community through residential or hospital treatment. Behavioral treatments can be an effective means to treat problem behavior. One of the most common behavioral treatments is differential reinforcement of alternative behavior, frequently implemented as functional communication training. Most demonstrations of behavioral treatments, including functional communication training, are conducted in highly controlled settings by trained therapists. When these treatments are implemented in community settings (e.g., an individual's home) by caregivers, they will be challenged, which can lead to the recurrence and sustained relapse of problem behavior. Recurrence and relapse can be the first steps in a chain that leads to treatment failure. Fortunately, some tactics have been designed to sustain treatment effectiveness and mitigate two forms of relapse (resurgence and renewal) that result from two of three primary treatment challenges. These tactics function as inoculation (i.e., make problem behavior less likely to return). However, there are no tactics designed to specifically mitigate a third form of relapse: reinstatement This project involves a novel inoculation tactic to mitigate reinstatement and protect against the third common treatment challenge: extinction errors. The tactic in question is based on substantial conceptual and empirical evidence from behavioral economics, as well as our pilot work. The project uses an innovative translational- treatment model to better understand which of the proposed tactics (our novel tactic or the default standard-of- care approach) better inoculates against extinction errors through real-world analogues. The use of a translational-treatment model is consistent with other research examining the role of basic processes in behavioral treatment when collateral effects are unknown, and will also engender a thorough examination of the proposed tactics. In Aim 1, we will establish a proxy response, apply treatment to that proxy response, and examine the effectiveness of progressive ratio training in inoculating against extinction errors and mitigating response- dependent reinstatement. In Aim 2, we will establish a proxy response, apply treatment to that proxy response, and examine the effectiveness of progressive ratio training in inoculating against extinction errors and mitigating response-independent reinstatement. Outcomes of this research could improve the current standard of care for behavioral treatments to make them more effective in community application, result in the development and validation of novel inoculation tactics, and significantly improve the lives of individuals with IDD.

NIH Research Projects · FY 2024 · 2024-09

PROJECT SUMMARY/ABSTRACT The Biomedical Research Support Facility (BRSF) is an essential core facility at Oakland University (OU). Investigators from six different departments and campus units rely on it to conduct basic and applied research. Originally constructed in 1999 (with support from NIH funding), it has been continually in use since OU took occupancy the following year. Not only has the building aged in terms of its mechanical systems and physical infrastructure, we are placing even heavier demands on it than ever before, precisely at the time when its systems are beginning to fail. Of the 19 investigators with current approved projects running in BRSF, nearly half of them were hired within the last three years. This is particularly true of the two autoclaves supporting research and day-to-day operations in BRSF. We have a large Getinge Castle M/C 3633 autoclave in the cage processing area that has not been operable for some time due to an ongoing inability to secure replacements for parts that have failed or worn out. A smaller Getinge Castle Model 133 autoclave with a bioseal is still operating between the (clean) anteroom and the (contaminated) procedures room in the BRSF biocontainment suite, but it suffers from the same problem in terms of replacement parts. This smaller autoclave is also increasingly used for research: two of our newly hired investigators each use adenovirus or lentivirus particles for transfection; another of our researchers works with stem cell therapeutics; a fourth does microbiological and gross anatomical work in rodent models of colitis. All four research teams generate medical waste that must be decontaminated before it is disposed of. OU has committed more than $1.2 million this fiscal year to replace the obsolete boilers and both the cage and tunnel washers in BRSF. This proposal seeks funding to replace the two autoclaves as well – since they connect to many of the same systems, it makes sense to tackle these replacements at or near the same time, to minimize the need for repeated service interruptions that will also impact ongoing research underway in BRSF. We have selected replacement models that are very similar to the obsolescent instruments they are designed to replace. The replacement instruments are much the same size as the existing models, use mostly the same size connections, and have roughly similar power requirements – one of several factors that influenced our choice for replacements. We are also requesting water-saving packages on both of the replacement instruments, as part of OU's sustainability initiative. We anticipate saving as much as 20,000 gallons of water annually with the replacement instruments, even with the increased load as our biomedical research enterprise expands.

NIH Research Projects · FY 2024 · 2024-09

Project Summary/Abstract TREM Like transcript (TLT-1), is a highly abundant platelet protein that mediates the earliest states of platelet activation. Inhibition of TLT-1 function is associated with bleeding in the inflammatory arena; however vascular hemostasis does not seem to be adversely affected. Our studies have shown that TLT-1 presents itself as a potential target to control thrombosis without the introduction of bleeding. However, to pursue the therapeutic aspects of TLT-1, we must first understand the mechanisms of TLT-1 function. This project is focused on identifying the critical signaling motifs of TLT-1 function. To accomplish this goal, we have outlined two specific AIMs: Aim 1: Characterize TLT-1 phosphorylation sites, Aim 2: Decipher the intracellular cues that regulate TLT-1 trafficking in platelets At the completion of these aims we will have a clear understanding of the importance of the platelet to regulation of edema and how we can manipulate platelet interactions to improve disease outcomes.

NSF Awards · FY 2024 · 2024-07

Bringing medical imaging technologies to remote areas of the world can be very challenging, creating stark disparities in patient access to potentially life-saving screening procedures, such as for breast cancer. Ultrasound, though, is portable and generally low cost. Recently, wireless ultrasound probes have revolutionized how and where ultrasound can be used, bringing the imaging method directly to the patient bedside. However, due to the complexity of the hardware, the data available from these wireless systems are limited and ultimately only represent a two-dimensional snapshot of a three-dimensional (3D) tumor. To address these challenges, the goal of this Engineering Research Initiation award is to develop a novel low-cost system capable of generating 3D ultrasound volumes at the patient bedside and quantitatively analyze images from this system to extract features that detect cancer. This award will also promote the development of a hands-on ultrasound curriculum at the undergraduate level as well as immersive and engaging ultrasound activities for elementary and middle school students, increasing awareness of ultrasound imaging and the role of engineers in the medical world. This project aims to engineer a low-cost, point-of-care, 3D wireless ultrasound system and determine optimal quantitative biomarkers that can be extracted from this system to diagnose breast cancer. To undertake this interdisciplinary work, the research will be focused into two main objectives. The first objective will establish quantitative tools using both traditional signal processing and artificial intelligence to extract ultrasound-derived biomarkers from wireless ultrasound data and evaluate their ability to improve breast cancer diagnosis. The second objective will focus on the development of a robust calibration, registration, and sensor fusion protocol to create 3D tissue volumes using a wireless ultrasound probe and a low-cost commercial sensor. The results of these studies have the potential to establish a new foundation for future innovation in accessible ultrasound technologies and increase access to critical cancer screening tools in low-resource settings. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2023-09

PROJECT SUMMARY The long-term goal of this project is to determine the neuronal and vascular mechanisms of visual impairment and myopia resulting from prematurity in order to develop preventive and therapeutic strategies. Prenatal and early postnatal vertebrate retinas generate correlated spontaneous neuronal activity, termed “retinal waves,” that are essential for normal neuronal development and vision. Premature retinal wave termination may contribute to preterm birth-associated vision problems and refractive errors. Preterm birth, in combination with postnatal oxy- gen therapy, can also cause retinal vascular complications known as retinopathy of prematurity (ROP). ROP is closely associated with incurable visual impairment and myopia in premature infants. The cellular and molecular mechanisms underlying the pathogeneses of eye disorders related to ROP and the early retinal wave activity termination are not yet well defined. Our objectives in this project are to define how spontaneous retinal waves mediate ocular growth before visual experience and how oxygen-induced retinopathy (OIR) causes vision impairment and myopia. Our preliminary data demonstrated that cholinergic retinal waves generated by starburst amacrine cells (SACs) can excite dopaminergic amacrine cells (DACs), the sole source of ocular dopamine—an ocular development regulator. We hypothesize that cholinergic waves drive normal eye development via dopamine signaling and that suppression of this pathway will disrupt normal ocular growth. In Aim 1, we will test this hypothesis by identifying the cholinergic wave–dopamine signaling pathway and assessing how this pathway impacts ocular growth. In addition, we have found that, in an OIR animal model, AII amacrine cells (AII-ACs) and DACs—two classes of inner retinal neurons that contribute to scotopic and photopic vision, respectively—were substantially lost. We hypothesize that the loss of AII-ACs and DACs in OIR causes myopia. In Aim 2, we will test this hypothesis by determining the relative contributions of AII-ACs and DACs to OIR-induced myopia and assessing the impact of OIR-induced visual impairments on myopia development. Expected outcomes include determining how retinal waves influence dopamine signaling to mediate ocular growth and how oxygen treatment perturbs the rod and cone signaling systems through the loss of retinal interneurons to cause vision loss and the development of myopia. The broader impact of this work on understanding the causes and mechanisms of preterm vision impairment and myopia in children will enable the rational discovery of new therapeutic interventions.