University Of California, San Diego

NIH Research Projects · FY 2026 · 2025-07

We will prospectively study the intersection between substance use, HIV and related co-morbidities in a cohort of people who use drugs (PWUD) in San Diego County (SD). For >25 years, Strathdee has studied the epidemiology of HIV and related co-infections among PWUD across North America, with N=500-1000 and annual retention ≥90%. Since 2020, our La Frontera I cohort situated on the U.S.-Mexico border has documented the highest HIV and HCV incidence among people who inject drugs in North America. Currently, HIV prevalence among former injectors in SD is 16% compared to 10% among current injectors. Consistent with other U.S. cities, we observed a dramatic shift from injection to non-injection of opiates in recent years, leading us to propose cohort expansion to non-injectors. Due to our location on a major drug trafficking corridor, we observe a wide range of substances (e.g., heroin, fentanyl, methamphetamine, xylazine, benzodiazepines). We previously leveraged La Frontera I to evaluate initiatives to improve uptake of PrEP, COVID-19 testing and vaccination. We propose: 1) To characterize trends and predictors of use of established and emerging drugs, drug use transitions (e.g., shifts from IDU to non-IDU & vice versa) and their impact on HIV incidence and utilization of HIV prevention and treatment. 2) To study prevalence and incidence of the following co-morbidities and their relationship to HIV incidence and utilization of HIV prevention and treatment: i) HCV; ii) STIs (i.e., syphilis, gonorrhea, Chlamydia, MPox), iii) neurobehavioral disturbances. 3) To evaluate the influence of structural interventions on HIV-related risk behaviors and utilization of HIV prevention and treatment including: i) new homelessness policies; ii) drug checking services; iii) vending machines. 4) To contribute to a shared database and biorepositories that serve as a platform for collaborations with end users and community partners. To meet these aims, we will continue to follow PWUD from La Frontera I who are actively using illicit substances, replenishing to arrive at 500 PWID and 500 PWUD (non-injectors) for a total sample of 1000. This will include subgroups vulnerable to HIV in SD (e.g., sex workers, people experiencing homelessness) among whom we expect 52 HIV seroconversions after 5 years of follow-up. Our cohort will include at least 50 PWUD living with HIV who will provide samples for viral load, sequencing and biobanking. All participants will undergo semi-annual interviews and specimen collection. SD is designated as a high priority jurisdiction for the Ending the HIV Epidemic Initiative (EHE) and a high intensity drug trafficking area by the DEA. La Frontera II leverages NIH-funded T32s, the California NeuroHIV Tissue Network, Last Gift Study brain/tissue repositories and the PREPARE Institute which tracks emerging and re-emerging infectious disease threats. Our work is aligned with priorities identified by RFA-DA-25-003, the NIH Office of AIDS Research and the EHE.

NSF Awards · FY 2025 · 2025-07

This project explores random curves and surfaces known as Schramm-Loewner evolution (SLE) and Liouville quantum gravity (LQG), which are central objects in modern probability theory and mathematical physics. The goal is to resolve longstanding problems arising from theoretical physics — specifically, bosonic string theory and conformal field theory. To this end, the PI will further develop the rich interplay between SLE and LQG. These methodological contributions are highly likely to find application in related problems. Additionally, this project will provide mentorship opportunities for undergraduate and graduate researchers. There are three main directions of research. First, Brownian surfaces are special LQG surfaces arising as the scaling limits of uniform random planar maps with specified topologies. A Brownian surface has a random modulus describing its conformal structure. The aim is to determine the law of the random modulus for each topology, thereby verifying a conjecture from bosonic string theory. Second, the conformal loop ensemble is a collection of SLE loops which arises as the scaling limit of lattice loop models at criticality. The objective is to derive exact formulas for various three-point functions of the conformal loop ensemble, and thus relate them to conformal field theories. Third, in bosonic string theory in physics, a string is a loop in d-dimensional space which evolves in time, tracing out a random surface described by LQG. The goal is to use LQG to give a mathematical construction of the bosonic string, and prove that its evolution is Markovian. 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/Abstract Antibodies are encoded by three loci: (i) the immunoglobulin heavy chain (Igh) locus, (ii) the immunoglobulin kappa (Igk locus and (iii) the immunoglobulin lambda (Igl locus. The Igh locus is segregated into variable (V), diversity (D), joining (J) and constant (C) regions. The Igk and Igl are comprised of V, J and C regions but lack D elements. The Igh and Igk loci utilize different mechanisms to generate VHDHJH or VkJk joints. Igh locus rearrangement is instructed by RAG scanning involving loop extrusion that pulls DHJH elements along chromatin until they align with VH gene segments to undergo VH-DHJH rearrangement. Vk-Jk locus rearrangement is regulated by changes in chromatin folding that brings distally-located Vk genes within close spatial proximity of Jk gene segments. The joining of Vk and Jk elements is regulated by enhancers, including the intronic Igk locus enhancer (iEκ), located in a genomic region separating Jk from Ck, and an enhancer, E34, that is positioned in the Igk variable region. iEk facilitates Vk-Jk joining involving Vk gene segments that span the entire Igk locus. E34 instructs Vk- Jk rearrangements involving Vk genes that are located nearby. We recently demonstrated that the E34 enhancer repositions a loop domain that harbors a subset of Vk genes into a recombination hub that is shared with Jk gene segments and the iEk enhancer. We showed the E34 deposits H3K27Ac across the enhancer region. We postulated that E34-mediated deposition of H3K27Ac constructs a confined spatial environment to prevent displacement of Vk from Jk gene segments (sub-diffusive motion). Here, we seek to determine how enhancers and epigenetics regulate Vk-Jk chromatin dynamics. In aim 1 we would develop a strategy to determine in quantitative terms, whether and how enhancers orchestrate Vk-Jk chromatin dynamics and instruct a sub-diffusive environment to enrich for Vk-Jk encounters. In aim 2 we would seek to determine whether epigenetic marks deposited across the E34 enhancer dictate Vk-Jk sub-diffusive motion and spatial confinement to increase Vk-Jk interaction- and Vk-Jk rearrangement- frequencies. The proposed method would enable us to determine how in 4D space enhancers and epigenetic modifications enrich for Vk-Jk encounters to generate diverse antibody repertoires.

NIH Research Projects · FY 2025 · 2025-07

Regulatory T (Treg) cells, a specialized immune population, are known for their role in maintaining immunological tolerance. Mounting evidence has suggested that Treg cells not only come in “different flavors” phenotypically and functionally and play distinct roles in different tissue microenvironments. Consistent with these findings, our previous analysis of tissue Treg cell transcriptome profiling data has revealed unexpectedly elevated expression of IL-27, specifically in gut-associated Treg cells isolated from inflammatory settings. In humans, genome-wide association studies have identified IL-27 as a candidate gene within a susceptibility locus for inflammatory bowel disorder (IBD). Significantly, less IL-27 was found in people harboring the risk alleles relative to those with the nonrisk alleles. These studies provided evidence linking IL-27 and IBD and suggested that the observed elevations in IL-27 in certain patients probably represent an anti-inflammatory response, albeit insufficient to control the ongoing intestinal inflammation. In this application, by using Treg cell-specific gene targeting approaches, our preliminary results have shown that Treg cell-derived IL-27 is crucial to control Th17 immunity particularly in the intestinal tissue. Further single-cell RNA sequencing (scRNA-seq) analysis has identified a CD83+CD62Llo Treg cell subset that is distinct from previously characterized intestinal Treg cell populations as the main IL-27 producers. Nevertheless, the molecular mechanisms and the environment factors that drive the expression of IL-27 specifically in gut Treg cells during inflammation remains poorly defined. Through employing molecular, biochemical, and immunological approaches with whole animal experimentation, we will first examine the Treg cell-intrinsic molecular mechanisms accounted for the induction of IL-27 in intestinal Treg cells particularly under inflammatory conditions. Next, as intestine is a special tissue location colonized by over 100 trillion commensal microorganisms that have been shown to be crucial in modulating Treg cell biology and T cell immunity, by employing cutting-edge microbiome technologies, as well as mice with microbiome interventions, we will identify and functionally validate the potential microbes that contribute to the induction of IL-27 in gut Treg cells. Accomplishing the aims proposed in this application will undoubtedly extend our fundamental knowledge the Treg cell-IL-27 axis in maintaining intestinal homeostasis and provide further insights into tissue specific-Treg cell-mediated immune regulation under different cellular and environmental settings.

NIH Research Projects · FY 2025 · 2025-07

Influenza A virus (IAV) remains a threat. With high pandemic potential, and two circulating strains in human populations, IAV has contributed to yearly morbidity and mortality despite its identification and isolation nearly 100 years ago in 1930. In addition to intense study of its surface proteins, hemagglutinin and neuraminidase (and the surface-exposed loop of the viral ion channel) to identify relevant targets of adaptive immunity, there have been considerable efforts to characterize the viral replication and transcription machinery. Such work has recently led to the development of new antivirals, and using this information has also led to an improved ability to leverage IAV as a vector in oncolytic therapy. In this proposal, we will expand on this prior work with a particular focus on the interactions with, and effects of, NS2 on viral sequence. The minimal IAV replication machinery consists of a heterotrimeric polymerase (PB1, PB2, and PA), and viral nucleoprotein (NP). Transfection into cells of this machinery with an appropriate RNA template (or polymerase I-driven plasmid expressing an appropriate RNA template) is sufficient to recapitulate both viral transcription and genome replication. This results in the production of three molecules, vRNA (- sense viral genomes), cRNA (+ sense viral antigenomes), and mRNA (+ sense viral transcripts). For IAV, mRNA possesses a host-derived cap, snatched by the endonuclease subunit, PA, and a polyA tail that is generated through a stuttering mechanism. While the minimal machinery is sufficient to produce all three molecules, it does so in amounts that are quite different than during infection. One of the largest differences is that during infection, each of the eight RNA segments comprising the IAV genome produces dramatically different amounts of mRNA, which is not the case during transfection. As an explanation for this divergence in behavior, it has been determined that expression of an additional IAV protein, NS2, modulates transcription and replication. Specifically, NS2 broadly decreases transcription in favor of replication. However, it does so unequally across the eight genomic segments of IAV, more consistent with what is observed during infection. As the characterized, minimal, viral promoter is identical across the eight IAV segments, this suggests NS2 must interact with an extended, uncharacterized, promoter sequence. Moreover, whether NS2 plays any role beyond regulating this switch is unclear. In this grant we will identify the sequence interface regulating NS2 interactions using a high-throughput mutation approach that we have already trialed successfully, explore our preliminary results that NS2 may modulate viral polymerase processivity, and, lastly, follow up on recent results from our group that NS2 may also impact viral polymerase fidelity. By the completion of this grant, we will have redefined the replication and transcription dynamics of IAV, providing novel interfaces for potential intervention, as well as providing essential information to those seeking to develop artificial viral platforms for therapeutics.

NIH Research Projects · FY 2025 · 2025-07

Posttraumatic stress disorder (PTSD) and substance use disorder (SUD) frequently co-occur. Existing research mainly focuses on symptoms among adults and lacks consideration of situational stress factors (SSFs), limiting its generalizability to other developmental periods (e.g., adolescence) for many Americans. PTSD and SUD depend on specific events—trauma exposure and substance use—often occurring during childhood/adolescence. Therefore, it is imperative to adopt a developmental psychopathological perspective to investigate the causes of this comorbidity, from events to symptoms, and include all Americans experiencing SSFs to generalize findings to all communities. Such an approach will yield a comprehensive understanding of comorbid PTSD + SUD, helping us determine the need for tailoring etiologic hypotheses to adolescents and efficiently allocate resources for early intervention and prevention for all Americans. We will use two largescale,longitudinal, multi-domain datasets: the Adolescent Brain Cognitive Development (ABCD) Study and the National Longitudinal Study of Adolescent to Adult Health (Add Health), to comprehensively evaluate the relationship between trauma exposure and substance use, incorporating SSFs, among the full population of Americans from childhood through adulthood. The study aims to test whether SSFs moderate adolescent trauma and substance use co-occurrence (AIM 1; K99 phase; ABCD), examine etiological trajectories of cooccurring trauma and substance use from event occurrence to symptom onset (AIM 2; K99 phase; Add Health), and test whether SSFs moderate the trajectory from event-level co-occurrence to PTSD+SUD symptom onset from childhood through adulthood (AIM 3; R00 phase; ABCD and Add Health). The strategic use of large, nationwide datasets—ABCD and Add Health—holds an unparalleled opportunity to comprehensively understand the developmental etiology of comorbid PTSD+SUD, generalizable to all Americans, from childhood through adulthood (ABCD: ages 9 – 18; Add Health: ages 12 – 42); a research endeavor that is extremely difficult and costly to initiate from scratch. Dr. Patel’s proposed training plan will enhance his existing skill set in comorbid PTSD+SUD. The mentorship team will provide necessary expertise and support to facilitate Dr. Patel’s transition to independence by acquiring training in developing stressfocused research questions and data analyses with a focus on co-occurring factors (training goal 1; advisors Dr. Gonzalez & Dr. Potter), developmental psychopathology of adolescent trauma exposure and substance use (training goal 2; co-mentor Dr. Brown), advanced within-youth statistical techniques (training goal 3; commentor Dr. Pelham), gaining clinical experience with co-occurring adolescent trauma and substance use (training goal 4; advisors Dr. Norman & Dr. Hanson), and engaging in professional development training and mentorship (5; all mentors and advisors). The proposed award will position Dr. Patel as one of the very few experts on the developmental psychopathological etiology of comorbid PTSD + SUD, integrating SSFs to generalize the etiology across the full population.

NIH Research Projects · FY 2025 · 2025-07

Project Summary/Abstract Our laboratory studies the subset (~16%) of T lymphocytes that naturally co-express 2 T cell antigen receptor (TCR) clonotypes, which have been demonstrated to have selectively increased reactivity against certain types of antigenic ligands. Despite the obvious implications for increased breadth of antigenic recognition by these cells, dual TCR T cells have been largely unstudied, owing to limited availability of tools for effectively studying them. Our group has developed several unique tools for studying dual TCR cells, and have provided evidence demonstrating that dual TCR expression is important in T cell development and that dual TCR cells have selective ability to recognize some types of ligands. Based on published and preliminary studies demonstrating functional effect of dual TCR cell co-expression in directing T cell differentiation and responses, we hypothesize that dual TCR co-expression may potentiate TCR signaling, possibly through cooperative effects. This could have significant impact on TCR-mediated signals instructing T cell differentiation and functional responses. Our development of the B6.TCRA-GFP/RFP dual TCR reporter mouse has been a unique and invaluable tool to identify unappreciated effects of dual TCR co-expression. This project proposes to generate and validating a novel transgenic mouse model combining a new B6.TCRA-AmCy reporter mouse with the well-established Nur77-GFP reporter model to enable assessment of TCR signal strength in single- and dual TCR cells. We propose that generating and validating these reagents will open significant new areas of investigation to understand fundamental T cell biology and the specific roles of dual TCR cells in protective and pathologic T cell function.

NIH Research Projects · FY 2025 · 2025-07

Project Summary Heterochromatin is a tightly packed form of DNA essential for chromosomal compaction, transcriptional silencing, genome stability, animal longevity, and tumor suppression. The mechanisms behind heterochromatin establishment remain incompletely understood. This project aims to investigate the initiation of heterochromatin, focusing on the interplay between Heterochromatin Protein 1 (HP1) and Signal Transducer and Activator of Transcription (STAT). Our previous research has shown that a fraction of STAT, not phosphorylated at the critical tyrosine residue around amino acid 700 (uSTAT), localizes in the nucleus in association with HP1. We demonstrated that STAT is essential for heterochromatin maintenance and that its activation by phosphorylation disrupts heterochromatin. Additionally, human uSTAT5A and STAT3 have been shown to promote heterochromatin formation and suppress tumor growth. Preliminary studies using chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) revealed that a significant amount of chromatin- bound Drosophila STAT is localized in constitutive heterochromatin. Loss of STAT leads to a global decrease in the levels of trimethylated histone 3 at lys9 (H3K9me3), a heterochromatin marker. Furthermore, when uSTAT is forced to bind to euchromatin, it can repress nearby genes in an HP1-dependent manner. These findings suggest that uSTAT plays a crucial role not only in maintaining but also in initiating heterochromatin formation. HP1 and H3K9me3 are hallmarks of heterochromatin, with HP1 being the central component. While recruiting HP1 to euchromatin is sufficient to initiate heterochromatin formation, HP1 does not bind DNA directly and has a weak affinity for H3K9me3. This suggests that HP1 may require DNA-binding protein factors for its initial recruitment to heterochromatic loci or to strengthen its binding to H3K9me3. Indeed, protein factors and RNA molecules have been implicated in heterochromatin establishment. We hypothesize that uSTAT is among the protein factors required for the establishment of a subset of heterochromatin. We will employ a combination of genomic, genetic, and biochemical tools to investigate the initial events leading to heterochromatin establishment. Understanding the molecular mechanisms of heterochromatin establishment could lead to novel cancer therapeutics through targeted epigenetic gene silencing.

NSF Awards · FY 2025 · 2025-07

In today’s rapidly evolving information technology landscape, network security is a critical pillar of cybersecurity. Preparing the next generation of IT research professionals to secure digital infrastructure requires theoretical knowledge, but also demands hands-on experience with real-world threats and data. This project bridges this gap through integration of advanced data science techniques and practical skills in cyberinfrastructure (CI) within the classroom. This project establishes the Cybersecurity Community Hub (C2Hub)—a platform for developing, delivering, and disseminating CI-enabled cybersecurity education and training resources. The project incorporates modular, open-source course materials for both undergraduate and graduate levels, including software tools, real-world datasets, and auto-graded assignments in the C2Hub platform. These modules are designed for seamless execution on NSF-funded CI platforms such as the National Research Platform and Expanse, making it easier for educators to incorporate hands-on CI use into their curricula. To support adoption and community building, the project offers educator workshops to provide training, gather feedback, and cultivate a network of educators sharing resources and best practices. The course materials and community practices developed through this project can serve as a national model for integrating CI into cybersecurity and STEM education. C2Hub promotes a data-driven approach to teaching and learning and expands the nation’s cybersecurity research workforce by empowering students from different institutional backgrounds to engage in cutting-edge data science and cybersecurity training. 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 · 2025-07

This project is about using recent advances in mathematics to improve lattice based cryptography. Lattice based cryptography is a foundation for advanced cryptographic schemes that are resistant to attacks by quantum computers. Secure cryptography is essential for digital communication, for example for ensuring the safe transfer of sensitive financial data. The new mathematical advance behind this project is the efficient construction of lattices that have both addition and multiplication operations and that are more densely packed than the ones now typically used in cryptography. The central goals of the project are to improve these constructions, to develop faster algorithms to operate on these lattices, and to build more efficient cryptographic applications using them. The technical advances in this project concern number fields with small root discriminants. This project will study the computational complexity of constructing such number fields and of performing arithmetic operations in them. Prior work on infinite families of number fields with small root discriminants has focused on existence theorems. This project will build on work of two of the P.I.s on efficient explicit constructions of such families. The goal is to improve these constructions using a variety of mathematical techniques including Galois cohomology, explicit Chebotarev theorems and recent advances on Hilbert's 12th problem via p-adic methods and modular forms. Another goal is to develop fast Fourier methods for performing arithmetic operations of the kind needed in cryptography. The relevance of number fields with small root discriminants was noted by Peikert and Rosen in 2006. They showed that such fields lead to very small connection factors relating the difficulty of solving the worst case of the short vector problem to the difficulty of solving the average case of the short integer solution problem. The cryptographic protocols to be studied using the rings of integers of the above fields include collision resistant hash functions, homomorphic commitment schemes, streaming authenticated data structures, zero-knowledge proof systems, and some types of digital signature schemes. 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

Summary Despite recent advances in treatment, the overall mortality for head and neck squamous cell carcinoma (HNSCC) remains high and current treatment regimens incur significant long-term morbidity. Targeting the immune checkpoint PD-1 with pembrolizumab and nivolumab has revolutionized HNSCC treatment. However, the overall response rate of these immunotherapies remains low, around 15-20%. This highlights the urgent need to identify novel therapeutic options for HNSCC to improve mortality, reduce morbidity, and enhance the activity and response rate of immune oncology (IO) approaches for HNSCC. We hypothesize that targeting HNSCC oncogenic signaling networks and disabling their immune evasive mechanisms may increase the response to anti-PD-1 treatment as part of a novel rational therapeutic strategy. In this regard, our laboratories contributed to the discovery that the persistent activation of the PI3K/mTOR signaling circuitry is the most frequent dysregulated signaling mechanism in HNSCC, and that mTOR inhibition exerts potent antitumor activity in multiple experimental HNSCC model systems and in two Phase 2 clinical trial. However, mTORi have shown limited activity in HNSCC in the metastatic, previously treated recurrent, and/or platinum-refractory settings. This highlights the urgent need to identify mechanisms of resistance to mTORi in advanced HNSCC cases, and new options sensitizing to mTORi, without increasing treatment-related toxicities. Our recent findings from multiple systems biology approaches converged to uncover that signaling by the HER receptor family (EGFR, HER2, and HER3) maintains persistent mTOR activation in HNSCC lesions, and that HER receptors blockade prevents mTORi adaptive resistance. We will now aim 1) to exploit synthetic lethal and gene interaction networks to expose druggable systems vulnerabilities upon HER receptors blockade as a precision therapeutic approach for HPV- HNSCC, and 2) to establish the impact of targeting the EGFR/HER3/HER2 (panHER) signaling network in HNSCC on the immune tumor microenvironment and response to ICB. Ultimately, we will exploit the emerging systems level understanding of HER family receptor oncosignaling circuitries in HNSCC for the development of novel rational combinations of targeted and immunotherapies.

NSF Awards · FY 2025 · 2025-07

The study of invariant geometries is a topic of fundamental importance in mathematics. These geometries arise naturally in many areas, including several complex variables (SCV), partial differential equations (PDE), and algebraic, complex, and differential geometry. This research project by the Principal Investigator is centered around a particular geometry - CR geometry - that arises in the study of SCV and complex geometry. It has deep and profound connections to central topics in mathematical and theoretical physics, including quantum field theory, general relativity, and string theory, as well as applications in systems engineering and control theory. The study of obstruction flatness, e.g., which has a prominent role in this project, has a direct link, via the Lorentzian Fefferman space, to the equations of motion in conformal gravity. The ideas and techniques that are needed for the investigations in this project come from a broad range of mathematical areas: complex analysis/geometry, PDE, and differential geometry; and, at the same time, the techniques and tools developed in this project will benefit these areas as well. The project will also provide interesting research topics and learning experiences for graduate students and postdocs. The seminar activity that will result from the project should be inspiring and stimulating for both students and other researchers. The goal of this mathematics research project is to study geometric and analytic aspects of invariant metrics and their potentials in complex analytic spaces, and related invariants in CR structures. The PI will investigate questions that are motivated by the classical and generalized Cheng-Yau and Ramadanov Conjectures concerning the Bergman metric and Bergman kernel, respectively, in strictly pseudoconvex domains in complex analytic spaces. He intends to work on the Cheng-Yau Conjecture for domains in Stein spaces with isolated singularities. The Ramadanov Conjecture, which asserts that strictly pseudoconvex domains with Bergman log flat boundaries are spherical, has been shown to fail in complex manifolds of dimension at least 3 (but holds true in dimension 2). This opens a compelling classification problem for domains with Bergman log flat boundaries that the PI intends to investigate. He also intends to study the asymptotic boundary behavior of invariant quantities such as the Bergman kernel, Bergman metric, and the Cheng-Yau solution to the complex Monge-Ampere equation. The investigations will elucidate how the boundary geometry influences analysis in complex spaces with boundaries. Additionally, the PI intends to pursue a theory for the Kohn Laplacian in domains on abstract CR manifolds. This is relevant to the local CR embedding problem in dimension 5. He also intends to continue his work on characterizing embeddability of compact CR 3-folds. The PI will investigate consequences of the global vanishing on a compact CR manifold of a higher order local invariant known as the obstruction function. This invariant is the obstruction to smooth extension to the boundary of the Cheng-Yau solution to the complex Monge-Ampere equation. In 3D, this invariant coincides with the trace at the boundary of the log-term in Fefferman's asymptotic expansion of the Bergman kernel and, hence, this problem is also connected with a strong form of the Ramadanov Conjecture. While the PI has made significant progress on the problem in 3D, it is still open in general. In higher dimensions, this problem is separate from the Ramadanov Conjecture, another problem that the PI intends to pursue. Additionally, he will investigate the relationship between the Bergman metric and the complete Kähler-Einstein metric in the setting of Stein spaces with singularities. A particular goal is to settle a generalized Cheng Conjecture in this context. 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

Summary/Abstract This R01 application is for a 5-year project to investigate the role of triggering receptor expressed on myeloid cells (TREM) 2 in Alzheimer's disease pathogenesis in people with HIV (PWH). Alzheimer's disease is the leading cause of dementia in the USA, yet despite many efforts, the cause remains unknown. Some evidence suggests that viral infections can trigger neuropathogenic cascades that lead to Alzheimer's disease. Consistent with this hypothesis, HIV infection is associated with premature aging and may increase the risk for age related neurodegenerative diseases such as Alzheimer's disease and amnestic minor cognitive impairment (aMCI). Our group and another group independently discovered reduced levels of TREM2 in the central nervous system of PWH. This was as significant discovery because TREM2 is an immunomodulatory receptor expressed by brain macrophages: microglia, perivascular macrophages, and infiltrating monocyte derived macrophages. Functional TREM2 surveys the brain for extracellular protein aggregates (Ab) and injured cells and modulates inflammation. Loss of function mutations in TREM2 are associated with increased risk for Alzheimer's disease. Alzheimer's disease-like pathology, including increased inflammatory cytokine expression and increased Ab, has been reported in postmortem brains of PWH. Despite these findings, how TREM2 functions in the brain during HIV-infection is unknown. Our new preliminary findings show that HIV infection and related inflammatory stimuli can alter TREM2 levels in macrophages. This mechanism for reduced TREM2 function may explain the published reports of increased levels of Ab and increased levels of inflammatory cytokines in postmortem brain tissues from PWH with neurocognitive impairment (NCI) compared to neurocognitively unimpaired (NUI) PWH. We also found that cannabinoids at appropriate doses can enhance TREM2 pathway expression and function in macrophages, which could explain why cannabis shows neuroprotective and anti-inflammatory effects in PWH. Understanding how HIV infection may lead to TREM2 dysfunction and Alzheimer's disease-like neuropathogenesis may provide clues to develop therapeutics for these neurodegenerative diseases. Therefore, we hypothesize that HIV modulates TREM2 signaling pathways in a manner that exacerbates neurodegeneration and inflammation, thereby accelerating Alzheimer's disease-like pathogenesis in PWH. This project aims to delineate the specific mechanisms by which HIV alters TREM2 function, exploring innovative pathways that may reveal novel therapeutic targets. This hypothesis will be tested in mice that model the intersection of aging, HIV, and AD neuropathogenesis (Aim 1), in cell culture models for brain macrophages after exposure to HIV, ART, and inflammatory stimuli (Aim 2), and in post-mortem brain tissues from PWH and people without HIV (PWoH), both with and without NCI and aMCI (Aim 3).

NIH Research Projects · FY 2025 · 2025-07

PROJECT SUMMARY / ABSTRACT Severe bacterial pneumonia can progress to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), in which the host hyperinflammatory immune response causes damage to the alveolar-capillary barrier in the lung. Although neutrophils are critical for host defense, their dysregulated recruitment, activation, and cell death can result in the excessive release of injurious mediators, which can cause collateral damage to the surrounding lung tissue and contribute to ALI / ARDS pathophysiology. While certain antibiotics are effective at killing pathogens, they do not specifically target the hyperinflammatory immune response. Thus, there is a significant knowledge gap in controlling neutrophil-driven inflammation in severe pneumonia while preserving neutrophils’ beneficial antibacterial functions. This study investigates a novel therapeutic concept, known as macrophage membrane-coated nanoparticles (MΦ-NPs), as a potential adjuvant therapy for treating severe bacterial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). MΦ-NPs consist of human macrophage cell membranes wrapped around a biodegradable PLGA polymeric core. Their macrophage surface receptors render them capable of neutralizing host cytokines, inflammatory pathogen-associated molecular patterns (PAMPs), and bacterial toxins. The central hypothesis of this proposal is that MΦ-NPs can protect lung tissue from neutrophil-driven inflammation and improve outcomes in severe MRSA pneumonia. Specifically, the two aims of this proposal are: 1) to test the hypothesis that MΦ-NPs modulate key neutrophil responses to MRSA to limit neutrophil-driven inflammation in vitro, and 2) to test the hypothesis that MΦ-NPs have in vivo efficacy in reducing inflammatory lung damage and improving survival in a murine model of severe MRSA pneumonia. These studies will enhance our understanding of neutrophilic inflammation and the translational potential of MΦ-NPs as a therapy for severe bacterial pneumonia caused by MRSA. The proposed research will occur in the Nizet laboratory, which has > 25 years of experience in taking collaborative approaches to study host-microbe interactions and novel therapeutics. Hunter will develop skills in nanoengineering, proteomics, immunohistochemistry, and mouse models of infectious diseases through mentorship, coursework, and hands-on experimentation with the Nizet lab and collaborators. He will also develop his clinical and professional skills through clinical volunteering, conference participation, and teaching.

NSF Awards · FY 2025 · 2025-07

Metric Riemannian geometry is a central subject in modern mathematics. The original concept dates back to Bernhard Riemann's famous Habilitation lecture "Ueber die hypothesen, welche der Geometrie zu Grunde liegen" (On the hypotheses which lie at the bases of geometry) delivered on 10 June 1854. The revolutionary creations in this lecture profoundly changed the global landscape of geometry. Specifically, Riemann proposed a novel strategy to generalize the geometry of surfaces to higher dimensions which he called Mannigfaltigkeiten (manifolds). A large variety of new notions and concepts were created: these include the notion of curvature which quantitatively measures how a space is curved, and the notion of geodesic which is a length-minimizing path connecting two points on a manifold. The studies of the metric structures of manifolds, what we now call metric Riemannian geometry, primarily focuses on the interplay between the global geometry of the underlying space and the metric structure, namely how the distance between two points can be realized or measured. This project is mainly concerned with the metric geometry of Einstein manifolds where the metric structures satisfy the Einstein equation in the theory of general relativity. The PI will integrate their research with training and mentorship at a variety of levels. This includes organizing summer workshops and mathematical retreats on Riemannian geometry; complex geometry and theoretical physics, and designing and developing new research oriented courses for undergraduate students. This project investigates the degenerations and quantitative behaviors of Einstein manifolds. In joint work with Song Sun, the PI has been working on the collapsing geometry of Einstein manifolds with special holonomy, leading to two major breakthroughs in the field: a complete classification of the Gromov-Hausdorff limits of the Einstein metrics on the K3 manifold, and a complete classification of asymptotic model geometries of gravitational instantons. The latter can be regarded as the bubble limits of the degenerating Einstein metrics on the K3 manifold. Building on this background, the PI will proceed to analogous questions in higher dimensions and investigate geometric structures for the degenerating Einstein metrics with generic holonomy in that setting. With a group of collaborators, the PI will also make advances in more refined geometry and moduli space problems regarding complete Calabi-Yau metrics. In a third direction, the PI will investigate the geometry and analysis of Poincare-Einstein spaces, which originated from the AdS/CFT correspondence in mathematical physics. The PI will focus on the singularity behaviors of degenerate operators on Poincare-Einstein manifolds, geometric finiteness and quantitative rigidity of Poincare-Einstein metrics, as well as regularity and degeneration theory of Poincare-Einstein metrics. 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

The objective of this proposal is a chairside molecular diagnostic to detect Enterococcus faecalis in endodontic infections and improve root canal outcomes. There are over 15 million root canals in the United States each year, but this treatment has a failure rate of up to 14%, which requires a repeat (secondary) root canal with major negative impacts on patients, providers, and budgets. One common reason for root canal failure is secondary endodontic infection. The bacterium E. faecalis underlies up to 77% of these secondary infections, and thus tools to detect E. faecalis chairside to confirm site preparation before closing the root canal could improve outcomes. Unfortunately, E. faecalis is currently only quantified with lengthy lab-based methods (i.e., PCR, microbiological testing): These cannot be done quickly or chairside, and clinicians are thus limited to using visual inspection and clinical experience, making secondary treatment unnecessarily common. We propose here a rapid colorimetric test that uses this pathogen’s natural protease signature as a trigger to produce signal. The outcome of this work will be a rapid chairside colorimetric diagnostic that reports the presence of E. faecalis via its characteristic extracellular protease GelE. This assay will confirm the absence of the pathogen so the canal can be sealed with confidence. Infected canals would be directed to more aggressive irrigation or treatment prior to filling and sealing the space. This will also prevent excessive cleaning therefore decreasing the chance of perforation. The research workflow will include two parts. Aim 1 will build the reagents for colorimetric coccolysin detection. We will synthesize and screen peptides to optimize the substrate unique to coccolysin cleavage. We will then use this substrate to tune nanoparticle aggregation/disassembly (and thus a color change) in the presence of the E. faecalis GelE protease. We hypothesize that the colorimetric signal (i.e., color change) will increase linearly with protease concentration (p < 0.05). Our goal is to detecting sub-nanomolar concentrations in less than 10 minutes. Aim 2 will validate the sensor with cultured bacteria and clinical endodontic samples collected by Dr. Roges. E. faecalis levels in the samples will be measured independently using PCR by Dr. Chen, and GelE protease concentrations will be confirmed using ELISA. We hypothesize that the colorimetric signal will correlate to these gold standard metrics at R2 > 0.80. The clinical impact is a chairside diagnostic to detect E. faecalis and enhance clinician and patient experience by decreasing the likelihood of secondary endodontic infection. The innovation is grounded is novel diagnostics for an important clinical scenario as well as novel nano-chemistry approaches that use nanoparticle disassembly for a color change, thus minimizing the impact of the sample matrix.

NSF Awards · FY 2025 · 2025-07

This I-Corps project focuses on an advanced drug discovery platform that employs artificial intelligence and multiscale simulations to identify promising drug candidates at a fraction of the cost of existing methods. This technology addresses the core challenge of extremely slow, expensive, and prone-to-failure drug discovery processes. The technology cuts costs and speeds up candidate optimization by running three parallel calculations simultaneously in a single and unified computational workflow. Unifying these calculations into a single workflow can screen thousands of potential drugs in a fraction of the time and reduce reliance on lab experiments. Faster identification of effective therapies improves patient outcomes, lowers healthcare costs, and enhances the ability of the nation to respond to emerging health threats. These societal and economic benefits extend to academic institutions, research universities, and biotechnology companies by facilitating cross‐disciplinary collaboration for accelerated drug discovery campaigns. This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of the technology. This solution is based on the development of an automated, artificial intelligence-driven, multiscale, end-to-end drug discovery pipeline that integrates high-throughput virtual screening of candidates, quantum mechanical refinement to accurately model drug-target interactions, molecular dynamics simulations for atomic-level insights into protein-ligand binding/unbinding events, and Brownian dynamics simulations to capture large-scale diffusion processes and binding events for protein-ligand and protein-protein interactions. This technology delivers rapid, accurate binding and unbinding thermodynamics and kinetics predictions for drug-target complexes by running artificial intelligence-enabled simulations in parallel within a single workflow. This platform is benchmarked on multiple therapeutically relevant targets, such as kinase and heat shock protein inhibitors, generating reproducible and accurate free energy estimates and multi-hour residence times in a fraction of the computation time required by current protocols, a capability not offered by any existing platform. Unlike traditional methods focusing only on binding affinity, the current approach efficiently and affordably predicts kinetics and thermodynamics for comprehensive candidate profiling, reducing trial-and-error and cutting lead optimization from months to days. 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 The pubertal transition marks a significant physiological, hormonal, and social change in animals and occurs at a very stereotyped timepoint within each species. However, the neural circuit mechanisms underlying the timing of puberty onset remain unknown. More generally, we know little about how the brain orchestrates long- timescale postnatal developmental timing, which is crucial for normal behavioral and social development. Puberty is initiated by the pulsatile release of gonadotropin releasing hormone (GnRH) from hypothalamic GnRH neurons. However, the causal neural mechanisms and stimuli underlying the developmental activation of GnRH neurons are poorly understood. Three neuronal populations have been speculated to control GnRH neuron activation, including RFamide-related peptide (RFRP) neurons, which I hypothesize control the timing of puberty initiation. Administration of the RFRP peptide is sufficient to delay puberty, and the population of neurons expressing RFRP decreases in cell number over development. However, RFRP neurons are poorly characterized, and their role in pubertal timing has not been systematically tested. The overarching goal of this proposal is to functionally and architecturally characterize this neuronal population and its developmental plasticity to delineate their role in pubertal timing and, more broadly, how coordinated changes in the brain mediate development. I propose to use state-of-the-art molecular genetic tools to establish the role of RFRP neurons in pubertal timing and delineate their molecular and connectomic changes through development. Fulfillment of my aims will provide the most comprehensive characterization of RFRP neurons to date, focusing on their role in puberty and using them as a model to understand how neural plasticity underlies postnatal development. This will lay the groundwork for a better understanding of the regulation of pubertal timing, providing potential therapeutic targets for pathologies such as precocious puberty and a better understanding of the most drastic transformation in postnatal development. The goal of my research career is to perform cutting-edge research to answer fundamental biological questions as a faculty in academia. The proposed goals will be accomplished in the UCSD laboratories of Dr. Dhananjay Bambah-Mukku – an expert on social behavior and genetic tools for neural circuit research, Dr. Alexander Kauffman – an expert on the neurobiology of puberty, and Dr. Edward Callaway – a pioneer of viral tract tracing methods. Together, we have outlined a comprehensive plan for the acquisition of technical and professional skills that will enable me to accomplish my scientific and career goals at UCSD, which provides an extraordinary environment with all the resources needed for my training and career development.

NIH Research Projects · FY 2025 · 2025-07

Project Abstract Drug abuse is a significant public health crisis, with over 106,000 drug-involved overdose deaths in the U.S. in 2021. Human genome-wide association studies (GWAS) have started to identify underlying causal genetic loci in addiction, but most of them sacrifice phenotypic granularity in order to obtain larger sample sizes. GWAS in model organisms such as N/NIH heterogeneous stock (HS) rats provide a valuable alternative that bridges this gap. However, determining the causal genes of addiction remains challenging because most GWAS studies focus on single nucleotide polymorphisms (SNPs) and overlook complex variants such as and tandem repeats (TRs) and structural variants (SVs). TRs and SVs are longer genome alterations compared to SNPs, which makes them hard to detect with short-read sequencing. This project proposes to address this serious limitation by using cutting-edge long reads sequence to discover and genotype TRs and SVs in support to investigate their roles in drug abuse using HS rats. The central hypothesis is that TRs and SVs contribute to the variability in gene expression, hence, affecting addiction-related behaviors in HS rats. In Aim 1, the TRs and SVs landscape in HS rats will be characterized using newly generated long reads in both inbred HS founders and outbred HS rats. Then, in Aim 2, a computational package will be developed to impute TRs and SVs to the whole population of over 20 thousand outbred HS rats. Finally, in Aim 3, quantitative trait loci mapping analysis will be performed to link TRs and SVs to gene expression and addiction-related behavioral traits. This innovative approach integrating long-read sequences focuses on underrepresented genetic variants, providing new insights into addiction genetics and potentially uncovering novel genetic mechanisms influencing addiction-related behaviors. Completion of this project will not only provide with the applicant with valuable training in behavioral genetics and bioinformatics and lead to potential therapeutic targets and strategies for preventing and treating drug abuse, but also create a community resource that will enhance ongoing rat genetic studies.

NIH Research Projects · FY 2025 · 2025-07

Airway remodeling is the term applied to the structural changes observed in the airway in asthma, and includes an increase in airway wall thickness which is associated with an increase in airway smooth muscle (ASM) mass, sub-epithelial fibrosis, mucus metaplasia of epithelial cells, abnormalities in composition of the extracellular matrix, and an increase in peribronchial vascularity. Although current NIH guidelines recommend maintaining a goal of normal lung function in asthma, current therapeutic strategies in asthma are not able to specifically target airway remodeling as the cellular and molecular mechanisms that result in remodeling are not well defined. Studies have also demonstrated that severe asthmatics with increased ASM on endobronchial biopsy have lower lung function (FEV1) compared to asthmatics with less ASM. Thus, ASM remodeling may contribute significantly to lower FEV1 in severe asthma. Although severe asthmatics comprise only approximately 5% of all asthmatics, they utilize a significant amount of health care resources (approximately 40% of the estimated $50 billion direct costs of asthma/year in the USA). As airway remodeling in severe asthma can contribute to lower lung function and a greater decline in lung function, there is an important need to identify mechanisms by which airway remodeling is mediated so that potential novel therapies could be directed at these pathways. The UCSD AADCRC will test the hypothesis that novel non- TH2-based inflammatory pathways in immune cells, inflammatory cells and epithelial cells mediate airway remodeling in severe asthma. In support of this overall hypothesis, Project 1 (Broide) has identified that Gasdermin A (GSDMA) is expressed at increased levels in epithelial cells in asthma, inhibits antiviral defense pathways in epithelium, which can trigger severe RV-induced asthma exacerbations with decline in lung function and airway remodeling. Project 2 (Croft) has identified that TNF family members LIGHT and TL1A (both increased expression in severe asthma) can directly induce human ASM and fibroblast remodeling underscoring the importance of this pathway to remodeling in severe asthma. Project 3 (Vijayanand) has identified increased frequency of a novel T cell population (i.e. cytotoxic TRM cells) in the airways of severe asthmatics, which may help to explain persistent T cell-driven inflammation and airway remodeling not due to known T cell populations (TH2 or TH1). We anticipate that each of the thee projects will identify selective pathways to airway remodeling, as well as shared pathways to remodeling that we have identified related to TRM cells, LIGHT/TL1A, and GSDMA. Novel pathways inducing airway remodeling in severe asthma will be tested in each project using human airway structural cells and TRM cells obtained by BAL, brushing, and endobronchial biopsy by “Severe Asthma Clinical Core B” from severe asthmatics and controls (mild asthma; non-asthma). Overall, these studies will identify potential novel therapeutic targets to inhibit airway remodeling and prevent decline in lung function in severe asthma.

NSF Awards · FY 2025 · 2025-07

The Collaborative Research in Computational Neuroscience (CRCNS) program supports a broad spectrum of investigators advancing computational understanding of nervous system structure and function, mechanisms underlying nervous system disorders, and computational strategies used by the nervous system. The goal of this meeting of CRCNS Principal Investigators is to foster interaction and collaboration across this vibrant community, highlighting the intellectual advances and broader impacts of CRCNS awardees. The meeting, scheduled for November 13-14 in La Jolla, California, is hosted by the University of California San Diego and includes poster presentations, talks, and plenary lectures, covering all areas of computational neuroscience represented by funded projects in the program. The meeting will include projects involving the United States, France, Germany, Israel, Japan, and Spain, sponsored by NSF and eight other partner agencies. This international meeting should have a significant impact on the participants and the future of computational neuroscience, including applications to artificial intelligence, biotechnology, and translational research. The meeting results will be publicized to the research community through publications and the meeting website. The broader impacts of the meeting are to facilitate progress in the field and stimulate conversations, connections, and collaborations that will lead toward better informed and effective CRCNS research community and resulting technologies that will be beneficial to all Americans. 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 · 2025-07

Science gateways are used by hundreds of thousands of researchers and students, supporting both publication-quality science and at-scale education. Science gateways involve research domains such as biomedical research, energy security, responsible AI development, and supply chain resilience. Gateways 2025 is the major event for the science gateway community in the US to discuss challenges and solutions, to identify new issues, to shape future directions for research, to foster exchange of ideas, standards and common requirements, and to support wider adoption of science gateways. Travel grants play a crucial role for students and early-career researchers by facilitating their access to expert knowledge and mentorship through conference sessions and networking opportunities. Gateways 2025 features various program formats such as keynotes, presentations, tutorials, demos, panels, posters and Bring Your Own Portal. Accepted submissions are published in open-access proceedings and accepted papers are invited to a special issue in a journal. The travel grant allows more students and early-career researchers to participate at Gateways 2025 and gives them access to expert knowledge and mentorship through conference sessions and networking opportunities. The topics covered by the Gateways conference series range from technical topics to use cases to related content such as usability or sustainability of science gateways. The building blocks of science gateway frameworks are re-usable in a broad range of research areas, as evident in widely used frameworks such as Hubzero and Tapis. The Gateways conference series sets the stage for learning, engaging and empowering the different stakeholders in the community who are science gateway users, developers and providers as well as funders and decision makers. 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 · 2025-07

This project supports research that looks to build upon concepts from aerospace composites engineering to create new geo-composites that combine geosynthetics and lightweight backfill materials with contrasting stiffnesses (lightweight cellular concrete, LCC and tire derived aggregate, TDA) in different geometric architectures with characteristics designed to reach desired objectives. Retaining walls have been constructed recently with TDA (a ductile recycled material that has high shear strength and damping but low modulus) and LCC (a brittle cementitious material that can be placed rapidly as a flowable fill) due to their lightweight nature, rapid construction, low cost, and good static response. However, there are fundamental concerns about the response of these materials during earthquakes, including excessive deformations of TDA, fracturing or loss of contact with reinforcements of LCC, and lack of clarity in whether lightweight backfills will behave as a rigid body due to their lower inertia or distort internally and dissipate energy. New infrastructure opportunities are sought by combining LCC together with TDA and geosynthetic reinforcements or separators to form geo-composites with features like high axial stiffness to support infrastructure but high shear flexibility to provide seismic or vibration isolation, accommodate earthquake loading, or absorb blast impacts. This research seeks to advance the seismic and static design of fill-type retaining systems with lightweight backfills. In addition to a training program for graduate students integrating aerospace composites and geotechnical engineering, high school and undergraduate students will be introduced to the concept of geo-composite backfills in construction through the development of an instructional shake table educational module that demonstrates the impacts of inertia and energy dissipation on the deformation of different backfills. The research objective of this project is to understand how TDA and LCC can be combined with geosynthetics to reach different geotechnical goals while at the same time addressing shortcomings identified in each of the individual backfills. This objective looks to be achieved by learning from composites engineering concepts to combine materials of different stiffness in creative geometries. This project will involve advanced numerical analyses using the discrete element model-bonded particle method (DEM-BPM), calibrated using results from element-scale experiments, to study the deformation response of different geo-composite configurations (e.g., mixtures, laminates, checkerboard, etc.) of LCC and TDA with geosynthetic interfaces under different modes of loading. The goals of the DEM-BPM simulations are to understand the deformation response and fracture initiation of LCC containing compressible air bubbles within brittle cement, and the deformation response of the planar, flexible TDA particles with high interface friction and edge interactions enhanced by exposed steel wires. The DEM-BPM analyses will be up-scaled and integrated into continuum-based constitutive models that looks to be used in commercial finite element software to design the geo-composite backfill materials to have different responses to static and seismic loading. The finite element simulations will be validated using shake table and vertical loading tests on scale-model geo-composites with TDA, LCC and geosynthetics in different configurations. Insights from the validated design simulations will be presented in industrial seminars that bring geotechnical engineers and TDA and LCC specialists. 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 · 2025-07

The United States semiconductor industry is facing a critical shortage of skilled workers, which threatens the nation’s ability to remain competitive in fields ranging from healthcare and defense to energy and communication. This project, the Semiconductor Workforce Advancement Nexus (SWAN), aims to address this urgent challenge by creating a scalable, university-based training model that focuses on technical training in collaboration with industry. Hosted at the University of California San Diego, the SWAN Center will offer students industry-endorsed coursework, mentorship, and career development aligned with real-world semiconductor job opportunities. Through partnerships with industry leaders such as SEMI and engagement with government and academic institutions, the program will help ensure the U.S. has a workforce capable of sustaining innovation, economic security, and national defense. This project will establish a prototype workforce training center at UC San Diego to explore best practices for preparing students for careers in the U.S. semiconductor industry. The SWAN Center will pilot a structured, integrated model combining (1) online technical instruction through SEMI University, (2) hands-on training via NanoFab workshops, (3) biweekly collaborative learning sessions to reinforce technical material, and (4) monthly leadership and communication workshops. The project also includes bimonthly career seminars and two annual networking events to connect students with industry professionals. Outcomes will be measured through surveys, pre/post assessments, job placement tracking, and participant feedback. Data will be synthesized to evaluate the effectiveness of training modalities, mentorship structures, and faculty-industry collaboration. The project aims to serve as a model for expanding semiconductor workforce development across institutions nationwide. 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 · 2025-07

Recent years have seen an unprecedented growth of the use of large data sets in various high impact fields, such as signal processing, imaging, and artificial intelligence. The task of extracting useful information from vast amounts of data typically leads to solving large-scale optimization problems. The size of such problems poses a variety of challenges for computation and is the bottleneck for further progress in applications. The investigator aims to advance techniques of large-scale optimization, with applications throughout science and engineering. The resulting algorithms will enable discovery of trends and patterns in the observed data and will enable accurate predictions about unobserved data. The technical aspects of the project combine elements from a variety of mathematical and applied disciplines, and an effective mix of numerical experimentation, teaching, and discovery is central to the proposal. Graduate students and postdocs will participate in all aspects of the project. Statistical estimation, signal processing, and learning from data rely on solving challenging optimization problems that are large-scale, stochastic, nonsmooth, and often nonconvex. Despite such irregularity, the domains of typical optimization problems decompose into “active manifolds”, which common algorithms “identify” in finite time, thereby opening the door to second-order acceleration strategies. This project studies the stochastic subgradient method and its common variants, which power modern large-scale optimization, and its numerous applications in data science and engineering. The goal of the project is to investigate how the performance of influential stochastic algorithms benefit from active manifolds and to develop novel algorithms that exploit this structure. The strategy for achieving this goal will be based on a recently discovered family of regularity conditions---originating in stratification theory and semi-algebraic geometry---that have been shown to hold along active manifolds in concrete circumstances. Utilizing such regularity conditions for active manifolds, the investigator will develop new efficiency guarantees for the subgradient method, show that the algorithm converges only to local minimizers while bypassing all extraneous saddle points, and establish the asymptotic distribution of the stochastic gradient iterates. In parallel, the investigator will explore the use of noise injection to learn the tangent spaces to the active manifold in order to accelerate the algorithm. This approach is highly interdisciplinary, relying on techniques from nonsmooth optimization, statistics, probability, and semialgebraic geometry. 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.