Johns Hopkins University

NIH Research Projects · FY 2026 · 2026-05

Project Summary. Multiple Myeloma (MM) is a disease characterized by the expansion of malignant plasma cells in the bone marrow. MM patients frequently demonstrate clinical responses to treatments consisting of proteasome inhibitors and immune modulatory drugs, hematopoietic bone marrow transplant, and monoclonal antibodies targeting several cell surface antigens, but all MM patients will eventually relapse, and disease eradication remains elusive. Central to this devastating trend is the persistence and evolution of therapy-resistance malignant plasma cells that arise following multiple therapies and the lack of effective non-invasive detection methods to assess disease status in the whole body. One rational approach to overcoming the intrinsic resistance seen with MM is to deliver a drug that is impervious to resistance directly to the tumor cells, such as targeted alpha-emitter therapy (TAT). TAT uses alpha-emitting radionuclides and causes largely irreparable double strand breaks that leads to selective cytotoxicity in cancer cells. However, there are substantial gaps in tools and knowledge in implementing TAT in MM as only few studies have examined the potential of TAT in MM and none with a focus on developing low molecular weight (LMW) theranostics, which show tractable pharmacokinetics than biologicals. Positron emission tomography (PET) is currently used to determine response to treatment and provide prognostic information in MM patients but more molecularly targeted imaging agents are needed to address the needs of MM patients. To address these unmet needs, our hypothesis is to develop a peptide-based first-in- class LMW theranostic pair for MM that targets cluster of differentiation 38 (CD38) protein, which is expressed uniformly and with high density in MM. Accordingly, our objectives are to create an 18F-labled PET imaging agent for improved prognostication of MM, and a potent actinium-225 (225Ac)-TAT to treat MM, in a single hybrid molecule. We will test our hypothesis in the following specific aims: 1) Develop the diagnostic component of a CD38 theranostic pair that fits within the standard clinical workflow; 2) Develop the therapeutic component of a CD38 theranostic pair; and 3) Characterize the therapeutic efficacy of CD38 TAT to control MM tumor growth. The proposal is innovative because it pursues the development of a first-in-class CD38 binding LMW theranostic pair and takes advantage of 18F for improved detection sensitivity and 225Ac for irreparable cell death. The proposed research is significant because it aims to develop imaging agents with potential to reduce unnecessary biopsies and treatments while also enhancing the prognostic value of minimal residual disease negativity and predicting clinical outcomes in MM. Moreover, this research also aims to develop complementary interventions to enhance existing therapeutic combinations by exploring new therapeutic agents that are highly specific, fundamentally different from current therapies, and overcome the resistance seen with current therapies.

NIH Research Projects · FY 2026 · 2026-04

X-ray computed tomography (CT) scanners are presently undergoing the largest architectural change since the introduction of multidetector-row (MD-)CT 26 years ago: they are moving from energy integrating detectors to photon counting detectors (PCDs). PCDs offer three times the spatial resolution of previous energy integrating detectors and also provide retrospective spectral imaging. In spite of their advantages, PCD CT faces two major barriers: (1) the cost of these systems is very high; and (2) the signal-to-noise ratio of spectral images is worse than that of older, dual-energy energy integrating detectors CT scanners. We propose to address these issues by switching semiconductor-based PCD to scintillator-based PCD. Scintillators recently developed are inexpensive, fast, and have excellent spectral responses. Each scintillator pixel is surrounded by optical reflectors that contain light spread. Optical reflectors do not detect x-rays, hence creating the dead space for the detector, which in turn, decrease the geometrical efficiency of detectors and increase noise. It has been a conventional belief that scintillator-based detectors would be too noisy (because the efficiency is lower than semiconductor). But our preliminary data shows that the improved spectral response outweighs the dead space and that the net effect for spectral imaging is positive. Moreover, we propose designs that will overcome the dead space in Aim 1. We propose to provide a proof-of-concept for scintillator-based PCD CT by developing theories and modeling detection physics and validating the performance against a clinical PCD CT system using a prototype PCD system in a table-top CT system. The specific aims are as follows. Aim 1: Optimize scintillator-based PCD design and develop algorithms using computer simulation. Aim 2: Develop a table-top CT system with a prototype scintillator-based PCD system. Aim 3: Assess scintillator-based PCD using a table-top CT system and compare against a clinical semiconductor-based PCD CT system. By the end of this project, we will have scintillator-based PCD algorithms with extensively validated performances. Our goals are to achieve noise variances that are >50% lower than semiconductor-based PCD for spectral imaging tasks (e.g., K-edge imaging), which corresponds to dose efficiency improvements by a factor of >2.0. Combined with a potential significant cost reduction compared to current semiconductor-based PCD, we will be ready to develop a gantry-rotating scintillator-based PCD CT with CT vendors.

NIH Research Projects · FY 2026 · 2026-04

PROJECT SUMMARY Without movement, we would be unable to interact with the world. All behaviors, including speech, writing, reaching, grasping, gaze, walking and posture require the coordinated activities of many motor areas. Further, sensory signals provide essential feedback to these motor areas, enabling accurate motor control and learning, as well as providing information vital for deciding future behaviors. As a result, understanding the sensorimotor control of even the most basic movements, like orienting toward a sudden sound or reaching to pick up a glass of water, is complex. Damage to these sensorimotor pathways can produce a wide range of debilitating neurological disorders including tremor, Parkinson's disease, ataxia, dystonia, and spasticity - all of which markedly decrease quality of life. The Society for the Neural Control of Movement (NCM) is a community of scientists, clinician-investigators and trainees engaged in research whose common goal is to understand how the brain controls movement and to address the deficits that occur in disease. NCM promotes a broad range of research using interdisciplinary approaches (e.g., neurophysiological, anatomical, molecular, computational, and behavioral), different animal models, and studies of intact subjects and those with neurological disorders. The inaugural NCM Meeting took place in 1991. The success of the society and its annual meeting has led to a continual growth in membership, meeting attendance, and the breadth of scientific content. With support through the NIH, the 2026 NCM meeting will make substantive progress towards furthering three main goals of the society: Aim 1) Stimulate new research approaches and collaborations among NCM meeting attendees by identifying new topics and appropriate scientists as speakers, Aim 2) Facilitate participation in NCM programming, membership, & leadership, and Aim 3) Promote and support the development of the next generation of motor control researchers by providing financial and career support for graduate students and post- doctoral fellows. Overall, the unique format of the annual NCM meeting, with its focus on interdisciplinary approaches, discussion, and scientific interaction in an intimate meeting environment, is of immeasurable value to furthering understanding of how the brain controls movement in both health and disease.

NIH Research Projects · FY 2026 · 2026-04

PROJECT SUMMARY Immune evasion is essential for the survival of any pathogen. One common mechanism of immune evasion, especially for extracellular pathogens, is antigenic variation, a process in which an organism continually changes an expressed surface antigen to escape clearance by the host’s adaptive immune response, drawing from a genomic repertoire of antigen-encoding genes. In many cases, the repertoire of antigens encoded in a pathogen’s genome is insufficient to sustain chronic infection; to survive, these pathogens must diversify their repertoire of antigen-encoding genes through mutation and recombination. The protozoan parasite Trypanosoma brucei, in addition to representing a major public health problem for sub-Saharan Africa, serves as an excellent model for understanding the mechanisms underlying antigen diversification. T. brucei, an extracellular parasite, evades clearance by host antibody by periodically “switching” its dense variant surface glycoprotein (VSG) coat, drawing from a large genomic repertoire of VSGs. Notably, only ~20% of this repertoire is comprised of intact VSGs; the rest is made up of pseudogenes or otherwise incomplete genes, leaving a relatively limited supply of VSGs for the parasite to draw from during infection. T. brucei extends its repertoire of antigens through a process of segmental gene conversion in which parts of individual VSG-encoding genes are recombined to generate new variants referred to as mosaic VSGs. These variants predominate at later stages of infection, but the mechanisms driving their formation have been nearly impossible to study until now. Our lab has optimized a targeted high-throughput sequencing method to characterize the full spectrum of recombination events occurring within a VSG, along with a Cas9-based method for inducing mosaic formation in vitro. Here, we propose to use these tools to undertake the first systematic study of mosaic VSG formation. The overall goal of this proposal is to understand the mechanisms driving VSG diversification in T. brucei. We hypothesize that both intrinsic and extrinsic factors shape the variants that arise during infection. For the first aim, we have generated a high-quality phased genome assembly for the pleomorphic EATRO1125 T. brucei strain that we will use to define the patterns of mosaic formation both in vitro, in the absence of host selective pressures, and in vivo, in the parasite’s natural environment. In the second aim, we will investigate the intrinsic factors driving VSG diversification by defining the minimal sequence requirements for VSG diversification and the cellular machinery that facilitates this process. In the third aim, we will investigate how parasite extrinsic factors shape the expressed mosaic VSG repertoire by evaluating which changes in a VSG facilitate immune evasion and whether certain host environments serve as hotspots for VSG diversification. The proposed study will provide insight into a process critical to the pathogenesis of many important pathogens. Long term, this work may help to identify new strategies for treatment of a variety of important infectious diseases.

NIH Research Projects · FY 2026 · 2026-04

Project Summary Neural population gain is a critical parameter in brain computation, influencing processes such as attention, learning, sensory adaptation, and decision-making. Despite its importance, existing neuromodulation technologies lack the temporal (milliseconds) and spatial (200 µm) precision needed to dynamically and locally modulate gain, creating a significant gap in our ability to study and manipulate neural circuits. This proposal addresses this gap by developing and refining ionic direct current (iDC) stimulation as a novel neuromodulation tool. Unlike existing methods such as optogenetics or drugs, iDC enables high-precision modulation of neural population gain while preserving natural activity, offering unparalleled potential for investigating and manipulating brain function. Our overarching goal is to optimize iDC for targeted modulation of neural population gain at the scale of cortical columns. To achieve this, we propose three independent but complementary aims. Aim 1 will develop computational models to predict the effects of iDC parameters (source locations, polarity, and relative amplitudes) on neural population gain. By integrating multiple biophysical assumptions within a 200 µm scale, these models will provide testable predictions to guide experimental designs. Aim 2 will experimentally validate iDC's ability to modulate gain, first in the anesthetized rat somatosensory cortex (Aim 2.1) and then in a behavioral model of tactile hypersensitivity using Shank3-/- mice (Aim 2.2). These experiments will explore iDC’s capacity to reduce cortical gain and alleviate behavioral deficits linked to excitatory-inhibitory imbalances. Aim 3 focuses on engineering a multichannel wireless iDC backpack system for chronic, multi-site gain modulation studies in rodents, enabling widespread adoption of this technology. Our innovative approach integrates computational modeling, experimental neuroscience, and cutting- edge engineering to develop a transformative tool for neuroscience research. This work has the potential to uncover causal links between neural population gain and behavior, advance our understanding of brain computation, and create new therapeutic avenues for gain-related disorders.

NIH Research Projects · FY 2026 · 2026-04

PROJECT SUMMARY/ABSTRACT Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is a long-term disabling condition with a wide range of symptoms, often triggered by acute infection. The CDC estimates that in 2022, over 3.5 million Americans are living with ME/CFS, and this number continues to increase as many Long COVID patients develop ME/CFS. Profound neurocognitive sequelae are highly prevalent in ME/CFS. The underlying pathophysiologic mechanism that drives neurocognitive impairments in post-infectious chronic conditions remains poorly understood, hindering the development of therapeutic interventions. Studies in chronic viral infections recognize that the trafficking of proinflammatory monocytes in the brain drives disruption of the blood-brain barrier and promotes a neuroinflammatory state. We hypothesize that post-SARS-CoV-2 onset ME/CFS patients and pre- pandemic ME/CFS patients have similar blood-brain barrier (BBB) disruption that is mechanistically linked to circulating proinflammatory analytes (cytokines and chemokines), altered BBB endothelial integrity, and a subtype of proinflammatory peripheral blood mononuclear cells (PBMCs) known as intermediate monocytes. Thus, disruption in BBB integrity promotes persistent neuroinflammation and altered neuronal activity, contributing to neuropsychiatric sequelae in both pre- and post-pandemic ME/CFS patients.Additionally, there is evidence supporting glymphatic system dysfunction in ME/CFS, which further contributes to the perpetuation of the neuroinflammatory state. We propose cross-sectional imaging to assess BBB integrity, with neuropsychiatric assessments and immunophenotyping in 100 post-SARS-CoV-2 onset ME/CFS patients and 100 who have pre- pandemic ME/CFS patients. In addition, we will incorporate 100 participants as a control group of SARS-CoV-2 infected individuals who fully recovered without lingering symptoms from our team NIH-funded similar study in a Long COVID cohort. First, we aim to assess BBB integrity in post-pandemic ME/CFS (vs. pre-pandemic ME/CFS) and its contribution to neuropsychiatric conditions. BBB integrity will be evaluated with a non-contrast magnetic resonance imaging technique that uses water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST), to determine BBB permeability to small molecules. We have shown this to be sensitive to BBB change in mild cognitive impairment and are currently using this technique in other neuro-infectious diseases. Second, we aim to assess cross-sectional links between circulating soluble markers, PBMC-associated markers, and BBB permeability to small molecules in post SARS CoV-2 onset ME/CFS patients and pre pandemic ME/CFS. We hypothesize that both groups will exhibit similar levels of soluble markers promoting PBMC trafficking to brain and promoting monocyte activation, disruption of soluble markers that promote endothelial integrity & higher levels of cell-surface proteins that promote PBMC diapedesis into brain will be associated with higher PS values and greater alterations in the cognitive and psychiatric domains. Findings will inform next steps in the development of therapeutic approaches to minimize neuroinflammation in Long COVID.

NSF Awards · FY 2026 · 2026-04

Computational imaging aims to recover meaningful visual information about an object or scene from measurements collected by an imaging system. In many important applications, however, those measurements are indirect, incomplete, and noisy, making it difficult to determine the true underlying image. For example, many three-dimensional microscopy applications would need to recover cellular structure from measurements acquired over only limited views. In such settings, the data may be consistent with many plausible images rather than a single unique solution. Yet existing methods typically produce only one reconstructed image and do not capture this ambiguity. As a result, they cannot indicate whether the image is trustworthy, where uncertainty is concentrated, or what other plausible images may also explain the measurements, all of which are important for scientific and clinical decision-making. Developing the next generation of computational imaging methods therefore requires a shift from single-answer reconstruction to probabilistic approaches that characterize the full range of plausible solutions. To address the need, this project will develop a novel provable, flexible, and scalable framework that combines physical forward models with generative diffusion models for computational imaging. The framework will recover the full distribution of image solutions consistent with the measured data, rather than only a single reconstruction, thereby enabling principled uncertainty characterization. The research will pursue three integrated directions: (i) developing a rigorous posterior sampling framework for imaging inverse problems with theoretical guarantees; (ii) designing flexible algorithms compatible with nonlinear and partially unknown forward models; and (iii) creating scalable methods for high-dimensional imaging. The project will draw on emerging connections between sampling and optimization to develop new reconstruction algorithms together with convergence analyses, while also producing practical methods based on gradient updates, proximal operators, and neural field representations. In collaboration with domain experts, the investigator will apply the developed methods to intensity diffraction tomography for three-dimensional live-cell imaging, optical coherence tomography for free-motion four-dimensional eye imaging, and quantitative magnetic resonance imaging for stroke diagnosis. The resulting theory and algorithms will advance probabilistic imaging and improve the reliability of computational imaging in scientific and biomedical applications. 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 · 2026-04

With the support from the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Professor Younan Xia of the Georgia Institute of Technology and Professor Emmanouil Mavrikakis of the University of Wisconsin-Madison will develop a knowledge base for achieving robust, reproducible, and scalable production of colloidal nanocrystals. Colloidal nanocrystals with well-controlled properties are beneficial to the U.S. economy and society. For example, the nanocrystals have potential applications as advanced catalytic materials essential to energy conversion and environmental protection, as well as production of important chemicals and pharmaceuticals. The multi-disciplinary and collaborative nature of this project will offer a natural vehicle to enrich the education and training experiences of all participants. The results from this project will be adapted to enhance classroom teaching, including the development of demonstrations (both animations and experiments) related to the key concepts of chemistry and chemical engineering. Through an integration of experimental studies and computational modeling, three methods will be developed and validated for realizing nanocrystal synthesis under both steady-state kinetics and one-shot injection. In the first method, the dissociation equilibrium of a weak acid is leveraged to maintain its conjugate base (the actual reductant) at a constant and controllable level. Due to the dissociation equilibrium, the conjugate base will remain at a fixed concentration until all the added acid is consumed. In the second method, an insoluble salt precursor is used to ensure that the metal ion (the actual precursor) in the reaction solution will stay at a constant level. The third method borrows the concept of controlled release from drug delivery by loading the precursor or reducing agent in polymer beads. Under zero-order release, the precursor or reducing agent in the reaction mixture will exist at a low and constant concentration as it will undergo immediate consumption upon release from the beads. When the other reactant is used in large excess to stay at a constant concentration, these methods will enable the establishment of steady-state kinetics. Along with experimental inquiries, computational studies will be conducted to achieve a better understanding of the dissolution, dissolution, reduction, and growth mechanisms. 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 · 2026-04

ABSTRACT Sinus node dysfunction (SND) is a significant heart rhythm disorder that affects both young patients with congenital heart conditions and adults due to aging or secondary complications from other heart diseases. For symptomatic patients, pacemaker implantation is often required, particularly in children, where it frequently indicates worsening heart function and poor clinical outcomes. Despite its high prevalence, the underlying causes and progression of SND remain poorly understood. A major challenge in advancing treatments is the lack of a reliable human model that effectively replicates the sinoatrial node and its dysfunction. This project aims to address this gap by utilizing human cardiac pacemaker organoids derived from iPSCs to model SND. We hypothesize that integrating nonmyocytes into these organoids plays a crucial role in accurately mimicking the sinoatrial node and the progression of SND. By applying constant or cyclic mechanical strain, we will simulate the disease environment to better understand its mechanisms. These organoids will mirror the cellular diversity of the native sinoatrial node, offering a rigorous platform to explore the etiology of SND. The ultimate goal is to identify key molecular targets that could lead to novel therapies, reducing the need for permanent pacemaker implants and improving patient outcomes.

NIH Research Projects · FY 2026 · 2026-04

PROJECT SUMMARY/ABSTRACT Parental opioid misuse presents a critical public health challenge, with strong evidence linking opioid misuse among parents to adverse outcomes for both parents and their children. Engagement in drug treatment with medications for opioid use disorder (MOUD) is a key strategy for improving outcomes in families affected by opioid misuse, as MOUD has been shown to improve child permanency and reduce child mortality. Despite this, many parents who misuse opioids and have dependent children (PWUO-DC) face significant barriers to initiating and sustaining MOUD. Social networks are a powerful, yet understudied, influence on MOUD engagement among PWUO-DC. These networks may offer essential support or present barriers to treatment engagement. The overarching goal of Dr. Lauren Dayton’s research career is to identify and leverage social network dynamics to improve the health and well-being of PWUO-DC and their children. The proposed K01 career development award will equip Dr. Dayton with the training and pilot data needed to become an independent investigator focused on developing network-based recovery models tailored for PWUO-DC. This exploratory sequential mixed-methods study, guided by the Implementation Mapping Framework will address key gaps in the literature by pursuing three research aims: 1) Examine how drug-free network members support PWUO-DC engagement and retention in MOUD and identify barriers to providing support; 2) Characterize the composition and functions of social networks of PWUO-DC to identify factors associated with their engagement in MOUD; and, 3) Develop and component-test an intervention that mobilizes drug-free network members to support MOUD engagement among PWUO-DC. The training plan addresses the additional methodological and content skills Dr. Dayton needs to develop as an independent investigator aiming to improve the health and well-being of PWUO-DC and their children. The four training areas are: (1) drug treatment models, (2) family-focused substance use research, (3) implementation science, and (4) ethical research with families affected by opioid misuse. She will be mentored by a multidisciplinary team of senior investigators with strong NIH-funded research and mentorship experience, and supported by a robust institutional environment with deep expertise in substance use, implementation science, and ethics. This research aligns with NIDA’s Strategic Objective 2.4: Advance the science of recovery support, by exploring social network stigma and other barriers to MOUD engagement and advancing the development of network-based support strategies. Findings from this study will identify strategies to mobilize PWUO-DC’s drug-free network members to improve MOUD engagement, which can inform scalable, family-based recovery interventions and improve the health outcomes of families impacted by opioid misuse.

NSF Awards · FY 2026 · 2026-04

This REU Site award to Johns Hopkins University, located in Baltimore, MD, will support the training of 12 interns for 10 weeks during each summer from 2026 to 2028. Research is conducted in various labs of the Rosetta Commons located throughout the United States and abroad. It is anticipated that a total of 36 students, primarily from schools with limited research opportunities, will be trained in the program. Students will learn how interdisciplinary, collaborative research is conducted, and all will present their work at scientific conferences. Upon completion of the REU program, students will have gained an understanding of how to investigate biological problems from a structural perspective; experienced computational molecular design including artificial intelligence approaches; acquired a solid foundation in research methodologies in biochemistry, biophysics, computational biology, machine learning, and molecular engineering; gained skills to collaborate with other scientists and engineers in other laboratories globally; and gained a deeper appreciation for the contributions that improved technology in these areas can make to society. The program will be assessed using the SALG URSSA questionnaire through Qualtrics. The NSF ETAP system will be used to register participants (https://www.nsfetap.gov/). Students will be tracked after the program to determine their career paths. The training students will receive is aligned with the NSF priorities in Biotechnology, Quantum Information Science and Artificial Intelligence. The research uses computational methods for prediction of the structure of biomolecules (which underlies their behavior and function) and the design of new biomolecules (important for materials, nanotechnology, and biotechnology). Example research projects include “Antibody engineering by deep learning,” “Protein design using generative methods,” “Enzyme design through quantum active site modeling and diffusive scaffold generation,” and “Cracking the human immune repertoire using AI.” The training program consists of a one-week bootcamp where students learn computer coding and structural biology, eight weeks of research in distributed labs (across the US and abroad), and a final week together at the annual Rosetta Conference. One training module includes quantum mechanical approaches for active site design, and one mentor’s research focuses on enzyme design, which can begin from quantum calculations of transition states. During the research period, students will complete an independent research project under the mentorship of a host lab, participate in weekly virtual journal clubs, prepare research proposals, and prepare a poster for presentation at the conference. All participants complete the Responsible Conduct of Research course. REU applications are reviewed and chosen by an admissions committee consisting of Rosetta Commons members at all career levels. 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 · 2026-04

Abstract People with HIV (PWH) who use methamphetamine (METH) experience disproportionately high rates of neurocognitive impairment and chronic neuroinflammation, even with suppressive antiretroviral therapy. Microglia are central to these CNS complications, yet the molecular mechanisms by which METH exacerbates HIV-induced microglial dysfunction remain poorly understood. A major limitation in the field has been the lack of integrative, systems-level studies capable of identifying key molecular regulators of neuroinflammation and viral persistence in the context of HIV and substance use comorbidity. Our preliminary studies implicate MECOM (MDS1 and EVI1 complex locus protein), a stress-responsive transcriptional regulator, as a potential mediator of METH-induced microglial reprogramming under HIV infection. We observed that METH alters HIV replication and cytokine production in iPSC-derived microglia, with persistent effects following their integration into brain organoids. Bulk transcriptomic analyses revealed MECOM upregulation under HIV/METH co-exposure, suggesting a role in neuroimmune dysregulation. This proposal combines integrated transcriptomic and proteomic (multi-omics) analyses with advanced human-derived models, including iPSC-derived microglia, neuroimmune organoids, and HIV-infected humanized NOG-hIL34 mice, to map and validate MECOM- associated networks. We will first define MECOM-regulated signaling pathways and protein interaction networks in HIV-infected microglia exposed to METH using integrative transcriptomic and proteomic analyses. Building on these findings, we will then determine the functional consequences of MECOM deletion in human-derived in vitro models and in HIV-infected humanized mice. By uncovering how METH alters MECOM-dependent signaling in HIV-infected microglia, this study will provide new mechanistic insight into HIV-associated neuroinflammation and identify candidate molecular targets to mitigate CNS complications in PWH with comorbid substance use.

NIH Research Projects · FY 2026 · 2026-04

Project Summary Phenomenal neurochemical changes occur during human brain maturation. These changes are both heterogenous across different brain regions and heterochronous for different metabolites during this period of growth. Investigating the neurometabolic trajectory of the healthy developing brain will help establish biomarkers for dysfunctional development and brain injuries. With high prevalence of cardiometabolic risk factors among women of reproductive age in the U.S., understanding the effects of these risk factors on infant brain oxidative stress and neurotransmission becomes critical. Key neurometabolites of interest include neurotransmitters and neuromodulators such as glutamate (Glu), gamma-aminobutyric acid (GABA), aspartate (Asp), and N- acetylaspartylglutamate (NAAG), antioxidants such as glutathione (GSH) and ascorbate (Asc), indicators of mitochondrial dysfunction lactate (Lac), and neuronal integrity N-acetylaspartate (NAA). Magnetic resonance spectroscopy (MRS) is the only non-invasive tool that can measure these metabolite levels in vivo. MRS techniques incorporating imaging (MRSI) extend spatial coverage and allow the spatial distribution of brain metabolites to be mapped. However, a lack of motion-immune advanced MRS/MRSI techniques for infants and young children to map multiple metabolites simultaneously has resulted in limited knowledge of neurochemistry of early brain development. This knowledge gap directly results from the technology gap, which must be prioritized to determine the neurometabolic trajectory of the developing brain. This project will help address these gaps using two approaches: i) determining the neurometabolic trajectory of the developing brain localized to a single voxel in the bilateral thalamus from 0-15 months of age and determining the effect of maternal cardiometabolic risk factors to the developing neurometabolic trajectory, both of these using the publicly available HEALthy Brain and Child Development (HBCD) study MRS data; and ii) by developing an advanced multi-metabolite edited MRSI technique with robust motion correction for the pediatric population that will enable mapping of the spatial distribution of neurometabolites across the developing brain. This Pathway to Independence Award will be supported by excellent career development resources at Johns Hopkins University, and training from a mentoring team of world experts in the field of pediatric and neurodevelopmental research, advanced edited MRS, and motion-correction methods for MRI. This project will generate novel motion-robust tools to study metabolic processes in pediatric populations and also leverage the HBCD study data to advance the understanding of pediatric neurobiology, potentially indicating biomarkers for deviations from healthy brain development.

NIH Research Projects · FY 2026 · 2026-04

During suppressive antiretroviral therapy (ART), HIV-1 persists in long-lived resting memory CD4+ T cells of children and young adults with perinatal HIV-1 as both intact and defective proviral genomes. The intact, replication-competent proviruses contribute to the latent reservoir and are a lifelong barrier to cure. In perinatal HIV-1, the reservoir is established early and shaped by unique immunologic factors. A growing body of evidence suggests that while defective proviruses cannot contribute to rebound in the absence of ART, these proviruses are transcriptionally and translationally active, potentially leading to adverse immune effects. However, the frequency, composition, and potential immunologic effects of defective proviruses across pediatric age groups remain poorly understood. In this proposal, we aim to characterize the defective proviral reservoir in children and young adults living with perinatal HIV-1 by determining the abundance and sequences of proviruses that are maintained for years despite ART and assessing their ability to produce viral mRNA and proteins. This project leverages well-characterized, bio-banked peripheral blood mononuclear cell (PBMC) and plasma specimens from pediatric HIV-1 cohorts to systematically characterize the landscape of defective proviruses in perinatal infection from infancy through adolescence. Our hypothesis is that in longstanding treated perinatal HIV-1, defective proviruses are transcriptionally and translationally active and drive persistent residual HIV-1 viremia during ART, promoting immune activation and exhaustion despite replication incompetence. Defective proviruses may also serve to produce decoy viral proteins that elicit autologous neutralizing antibodies, thereby reducing the efficacy of autologous neutralization of the latent reservoir. We propose three specific aims. In Aim 1, we will quantify and characterize intact and defective proviruses across pediatric age groups using near full-length single genome sequencing. In Aim 2, we will assess the transcriptional activity of defective proviruses following ex vivo stimulation in co-culture for HIV-1 mRNA analyses and their correlation with immunologic and clinical measures, including markers of immune activation and exhaustion. We will then compare it to sequences from low level plasma viremia to determine whether defectives are the source. In Aim 3, we will perform the quantitative viral outgrowth assay (QVOA) with the ultrasensitive p24 Simoa assay to identify if high- and low-level p24 producing wells are harboring intact or defective proviruses. We will then determine whether env-pseudotyped virus derived from intact or defective proviral sequences can be neutralized with autologous plasma IgG. By integrating molecular virology and immunology profiling in a pediatric context, this study will generate novel insights into the role of defective proviruses in HIV-1 persistence in children. Our findings will inform the design of age-specific cure strategies and contribute to the broader goal of ART-free remission in children with perinatal HIV-1 towards a life free of co-morbidities.

NSF Awards · FY 2026 · 2026-04

Safe, affordable, and long-lasting batteries are essential to the U.S. energy infrastructure. Aqueous zinc batteries use a non-flammable electrolyte and earth-abundant materials, which makes them a strong candidate for grid storage. However, they have a relatively short lifetime. This CAREER project will conduct experiments to control metal growth at the battery’s anode so that batteries remain stable over long periods. The research will yield design principles that explain how electrolyte additives delay battery degradation. Outcomes from the project will benefit other battery systems (e.g. Li, Na, Mg). The findings will impact related fields such as electrocatalysis and corrosion science. The project will integrate research with education by training students in advanced materials science and electrochemistry. Through research-driven mentoring and outreach activities (e.g. differentiated instruction, hands-on modules, and scaffolded mentoring pipelines), the project will help prepare a skilled workforce capable of addressing pressing energy challenges. This project will establish a predictive mechanistic framework connecting additive chemistry, electrodeposited zinc structures, and their interfacial evolution during electrochemical cycling. The project will pursue three objectives: (1) determine how liquid-liquid and liquid-solid molecular interactions modify surface energies and direct growth pathways; (2) reveal how electric field strength governs ion diffusion and deposition kinetics; and (3) identify how atomic arrangement and defect populations influence dendrite initiation and interfacial reactions. Engineered zinc anodes will serve as model platforms to interrogate structure-property relationships. Operando characterization combined with cycle-resolved post-mortem analysis will track structural, morphological and chemical evolution from early to extended cycling, enabling identification of degradation onset and mechanisms. By correlating additive chemistry with growth behavior and long-term stability, the project will transform additive selection from empirical practice to mechanism-guided design. The resulting chemistry-structure-property relationships are expected to provide transferable principles for controlled electrodeposition across a broad class of metal systems, advancing the scientific foundation of next-generation rechargeable batteries. 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 · 2026-04

PROJECT SUMMARY The proposed fellowship aims to prepare the applicant, Ananya Bhaktaram, for a career as a leading mixed methods researcher who examines the influence of social and spatial factors on social relationships and health. To develop the skillset necessary to become a leading expert, Ms. Bhaktaram proposes to investigate social and spatial factors that influence social connectedness and mental health, substance use, and HIV- related behaviors and outcomes in people living with HIV (PLWH) and populations highly affected by HIV (PHAH). Ms. Bhaktaram will conduct the proposed research while engaging in individualized mentorship, by a team of complementary experts to target the following training objectives: 1) Build competence in qualitative methodologies, and mixed methods approaches; 2) Enhance expertise in theory-driven geospatial analysis; 3) Advance expertise in advanced quantitative methods; 4) Cultivate a strong foundation in research ethics; 5) Engage in professional development opportunities to ensure success as an independent researcher. The proposed research is highly relevant for addressing mental health, substance use, and HIV comorbidities among PLWH/PHAH. Loneliness and social isolation have comparable levels of risk to health and premature death as smoking and obesity. Social connectedness is an important comorbid risk factor for poor/worse HIV- related outcomes, as social connections can serve as protective factors by acting as sources of resource and instrumental support. PLWH/PHAH report higher levels of loneliness and social isolation. Gaining insight into the social and spatial factors that influence social connectedness will allow for better assessment of future intervention points to improve mental health, substance use, and HIV-related comorbidities. To address these gaps, the proposed research will use data collected by Dr. Carl Latkin’s (Sponsor) research team at the Lighthouse to 1) Assess associations between social connection, mental health, substance use, and HIV-related behaviors and outcomes in PLWH/PHAH; 2) Explore social and spatial dynamics that characterize, facilitate, and hinder social connectedness among PLWH/PHAH; 3) Examine the relationship between spatial factors, social connectedness, HIV, and mental health related outcomes. Findings from this study will provide insight into the social and geographic factors that influence loneliness and social isolation to inform measurement and targeted strategies for preventive interventions, while offering conceptual insight that can improve the understanding of the distinct pathways of loneliness and social isolation. The proposed research aligns with Goals 2 and 3 of the NIMH’s Strategic Plan by providing conceptual and contextual evidence to understand mental illness trajectories and enhance prevention strategies to improve mental health, substance use, and HIV comorbidities in PLWH/PHAH.

NSF Awards · FY 2026 · 2026-04

This award will support a workshop to bring together principal investigators supported by NSF Trailblazer Engineering Impact Award program, also known as NSF Trailblazer. The principal investigators are thought leaders on topics ranging from biotech and robotics – areas of national need that are important for U.S. leadership in high technology. Over the two-day event, the principal investigators will brainstorm future research directions in high technology areas important for the U.S. The workshop will also include students of principal investigators and involve them in the visioning process. These discussions will promote a culture of creativity and risk-taking that align with the NSF mission to advance U.S. leadership in science and engineering. The Trailblazer Engineering Impact Award (NSF Trailblazer) Workshop will bring together current awardees of the NSF Trailblazer program for two days of structured dialogue and collaboration. The workshop will provide a dedicated forum for sharing transformative research directions, exchanging lessons learned, and exploring convergence opportunities across diverse engineering domains that address national research needs in emerging technologies, particularly in diverse areas of bioengineering, hazards & resilience, quantum science & computing, semiconductors, and robotics. Through presentations, interactive sessions, and collaborative activities, participants will collectively articulate emerging themes and future research visions aligned with the goals of the NSF Trailblazer program. By amplifying communication and collaboration within this unique community, the event will accelerate the translation of bold ideas into impactful directions and inform future priorities for transformative engineering. Outputs such as a collaboratively authored perspective document and recorded sessions will extend the reach of these discussions, promoting a culture of creativity and risk-taking that aligns with the NSF mission to advance U.S. leadership in science and 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.

NSF Awards · FY 2026 · 2026-04

Food production relies heavily on fertilizers. Most fertilizers are based on ammonia. Its production occurs at high temperature and pressure. This generates a significant amount of carbon dioxide. Some bacteria can fix nitrogen in the atmosphere. They convert it into ammonia. The natural process is slow, and the bacteria do not secrete much of the ammonia. Electrical stimulation can increase ammonia production and secretion in these bacteria. This CARRER project will use experiments and computations to understand how electrochemical stimulation works. Results will guide development of a low cost, low energy process that can be implemented on individual farms. The project involves a collaboration with the Baltimore Polytechnic High School. The process developed will be tested by high school students in their on-campus garden The roles of electrochemistry and biology in promoting nitrogen fixation must be unveiled to provide a path forward for decentralized bioelectrochemical ammonia production. The project is designed to unravel the regulatory mechanisms controlling the rate of ammonia production in nitrogen-fixing bacteria in response to exogenous electrochemical stimuli. The goal is to accelerate the development of small-scale bioelectrochemical production of nitrogen-based fertilizers directly in the field. A combination of experimental characterization and metabolic modeling will be used to correlate nitrogen fixation, electroactivity, and other key metabolic functionalities to identify how and why electrochemical stimuli facilitate biochemical ammonia synthesis. A reactor will be designed to take advantage of this process. Once the reactor is constructed it will be tested at a local high school. It will be used to generate ammonia that is used to fertilize plants in their garden. High school students will be trained to operate the equipment. They will also learn about the science and engineering behind the reactor. This project is expected to demonstrate a novel hybrid system for biomanufacturing. This could become the basis for the design of novel biomanufacturing utilizing bioelectrochemical processes. 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 · 2026-04

PROJECT SUMMARY Vascular calcification serves as the primary risk factor for predicting cardiovascular events. It involves arterial calcification, an actively regulated process mediated by cells, resembling physiological biomineralization but with impaired resorption. The vessel wall contains “calcifying vascular progenitor cells” that react to pro- calcific signals such as inflammation or infection. They then differentiate into osteoblast-like cells, which produce minerals and matrix in the vessel wall. The bulk of progenitor cells within the vasculature reside in the microanatomic progenitor niche, the tunica adventitia. Under normal conditions, these progenitors regulate vascular homeostasis and remodeling. The identity, location, function, and regulatory mechanism of adventitial progenitor cells in vascular calcification remain poorly studied. Further, uncovering the niche- specific role of adventitial progenitors in vessel calcification will guide the development of targeted therapeutic strategies. Recently, our integrated transcriptomic study on normal human blood vessel adventitia discovered a cell surface marker to typify adventitial progenitor cells. This previously undescribed marker in adventitial cell biology is Endothelial Protein C Receptor (CD201). CD201-expressing progenitor cells are spatially localized in the outer layer of the adventitia, and their expression level dictates the osteogenic potential of these cells. These recent observations raised questions regarding their role in the progression of vascular calcification and are comprehensively investigated in the present K99/R00 proposal. To achieve this, integrated spatial transcriptomics and single-cell RNA sequencing-based transcriptomic mapping of the human calcified vessel with implications of CD201+CD34+ adventitial cells in calcification will be initially performed. Additionally, reporter mice with nephrectomy-induced calcification will be also examined (Aim 1, K99 Phase). Secondly, a detailed in vitro functional characterization of FACS purified CD201High/Low cells from human calcified and healthy vessels will be performed, along with CD201 cell ablation in mouse calcification model to determine the functional role of the cell in calcification (Aim 2, K99 Phase). Lastly, the underlying signaling mechanism regulating CD201-expressing cells to be pro-calcific is investigated by CRISPR/Cas9 gene knockdowns, genetic mice calcification models, and integrated transcriptomics (Aim 3, R00 phase). Completing the proposal will greatly improve the knowledge of adventitial progenitor cell-mediated vessel calcification. The proposed research and training plan aligns with my long-term research objective. It will also significantly contribute to my scientific and career goals of establishing an independent research career in blood vessel resident stem cells and their role in vascular pathology.

NIH Research Projects · FY 2026 · 2026-04

The order Rickettsiales comprises arthropod-associated, obligate intracellular bacteria that are constrained to grow within a eukaryotic host as a result of substantial genome reduction. Their obligate intracellular lifestyle imposes challenges in culturing, genetically manipulating, and imaging these species. As a result, our understanding of fundamental aspects of rickettsial cell biology is limited. The Rickettsiales include a growing number of important human pathogens, however, and a mechanistic understanding of growth and cellular organization would potentiate therapeutic strategies to control rickettsial disease. Within the Rickettsia genus, the Spotted Fever Group (SFG) includes tick-borne human pathogens that cause diseases ranging from mild to life-threatening. Among the SFG bacteria, Rickettsia parkeri causes a relatively mild disease and presents a tractable model for probing the cell biology of this group. Interestingly, despite its reduced genome and lack of obvious morphological polarity, R. parkeri and other Rickettsiales encode putative cell polarity factors, including the polar organizing protein PopZ. We hypothesize that R. parkeri and other Rickettsiales exploit cell polarity to promote their intracellular growth and interactions with a host and that PopZ is important for establishing cell polarity in this group. Here, we propose to identify the suite of polar proteins in R. parkeri and functionally characterize PopZ’s role in growth and host interactions. In Aim 1, we will leverage proximity labeling to comprehensively identify the polar protein repertoire in R. parkeri and will validate putative polar proteins. In Aim 2, will leverage a transposon mutant of popZ to characterize the function of PopZ in fundamental events during R. parkeri growth and interactions with a host cell. Completion of this project will provide foundational knowledge on the mechanisms and function of cell polarity in an important tick-borne, obligate intracellular pathogen that may aid in the design of new antibacterial therapeutic approaches.

NIH Research Projects · FY 2026 · 2026-04

Project Summary/Abstract Decision making is a core cognitive process underlying myriad behaviors in day-to-day life. While great strides have been made in uncovering elements of the neural processes underlying decision making, key questions remain, especially related to the type of complex multi-attribute decisions that are common in the real world. Our novel task isolates each piece of information related to the value of options and requires subjects to view these attributes of options one at a time. Because of this design, we can monitor attention throughout and study the neural responses at each stage. This task also presents the distinct advantage of being viable for both human subjects and non-human primates. Already, we have gained key insights from recordings of neuronal activity in the pre-supplementary motor area (preSMA) of macaques performing the task. We found that preSMA neurons encode action value signals that accumulate information about the options. We also discovered that the focus of attention plays a key role in the value estimation process in these neurons. Attention both uniformly enhances the activity of neurons when the option in their preferred spatial position is attended and increases the gain of value representation in these neurons. With fundamentally the same task, we have collected data from patients undergoing intracranial recordings as part of their treatment for medically intractable focal epilepsy. With broad coverage of the brain across the population of patients, we have been able to identify a number of brain regions involved in different aspects of the task. Now, we can combine the advantages of both data sets to make additional progress. First, in Aim 1, I will implement a computational model for Attention Modulated Multi- Attribute Decisions (AM-MAD) consistent with the observed activity patterns in the preSMA data. This model will allow us to test the hypothesis that the observed forms of attentional modulation of value representation serve to prevent premature choices by allowing attended options to overcome inhibition. In Aim 2, broader networks for value estimation and option selection will be identified from the human sEEG data using a set of dimensionality reduction tools. This approach should reveal whether similar attentional modulation of value representation is present in corresponding areas in humans, as well as how these factors influence activity in other areas. Finally, in Aim 3, I will use new tools that have been developed for causal inference and are ideally suited to multi- channel intracranial recordings. This will allow us to study the flow of information through large-scale networks in the brain and test whether regions that show activity changes related to specific aspects of the task are directly interacting, e.g. whether activity in premotor areas is driven by both attention- and value-encoding frontal areas. With this additional information, the AM-MAD model will be refined with more detail about value and attention- related inputs. Together, this will serve to both advance our understanding of the neural mechanisms of attention in multi-attribute decision making and establish a set of tools that will be broadly applicable for studying cognitive processes across species and recording modalities.

NIH Research Projects · FY 2026 · 2026-04

Project Summary: Clathrin-mediated endocytosis (CME) is an essential pathway used by all eukaryotes for the transport of extracellular cargo into the cell. By controlling many of the signals that are transmitted between cells, CME is a key component in the development of organisms and neurotransmission. Although the basic mechanism of clathrin-coated vesicle formation is known, the process is sensitive to membrane composition and mechanics, and the concentrations, interactions, and chemical modifications of dozens of cytoplasmic proteins and cargo receptors. Thus key outstanding questions remain: how does cargo control the nucleation and growth of clathrin-coated structures, thus ensuring proper uptake in response to changing stimuli from the external environment? While formation of clathrin-coated structures in cells is clearly linked to cargo levels, this coupling is not retained in vitro, where structures assemble without any cargo present. Establishing the mechanisms and frequency whereby clathrin-coat remodeling can drive productive vesicle formation is critical to understanding when cargo is internalized in healthy or diseased cells. The problem is a natural target for biophysical modeling because the fundamental structure of the problem (the clathrin cage) is known, but predicting how cargo uptake depends on the lipid and cargo composition and the mechanical properties of the membrane is difficult because of the nonlinear coupling between protein assembly and mechanics. Our proposed work will determine when and how lipid and cargo binding will control nucleation and growth of clathrin coated structures. We will address an open question on how curved vesicles can emerge from initially flat lattices in time. Our simulations will predict responses and rescue from PIP2 and cargo inhibition, where clathrin-coat formation effectively terminates in cells, with experimental tests from our expert collaborators. We will quantify the role of clathrin polymerization forces and cooperativity in controlling nucleation on membranes, as well as how it responds to changes to membrane rigidity. We will work with our experimental collaborators to iteratively refine our model against new conditions. The impact of this proposal will be a validated model of CME that can be used to predict cargo receptor uptake in response to external stimuli and environmental changes that directly alter the plasma membrane. The methods and mechanistic insights from this work on CME will transfer to other pathways like cell division, intracellular trafficking, and viral budding, where proteins must similarly sense the membrane environment to ensure assembly at the right time and place.

NIH Research Projects · FY 2026 · 2026-04

SUMMARY Infections can have a significant negative impact on a person’s health even long after the pathogen is cleared from the host. Borrelia burgdorferi (Bb) the causative agent of Lyme disease causes persistent, non-resolving infections in laboratory mice. Previous work has identified significant immune suppression in infected mice, explaining the lack of bacterial clearance. This study is to explore our unexpected finding that Bb infection of mice causes a “leaky gut syndrome”, including endotoxemia, changes to the gut microbiome and fecal short- chain fatty acids. The mice demonstrate extensive hyper-gammaglobulinemia, including increased autoreactive IgG that appear resistant to antibiotic treatment and they lack the ability to generate robust T-dependent antibody responses, suggesting significant long-term effects on humoral immunity that may not resolve with the removal of the pathogen. The objective of this proposal is to define the impact of Bb infection-induced changes in gastrointestinal barrier function and microbiota on immune system health. Specifically, we will test our hypothesis that Bb infection-induced gut barrier dysfunction, dysbiosis, and endotoxemia result in prolonged immune dysfunction, affecting immune system health and the induction of protective immunity. Specific Aim 1 is to define the impact of Bb infection-induced gut barrier disruption on immune system health, testing the extent to which Bb infection-induced changes to the gut barrier alone contribute to Bb infection-induced alterations in immune homeostasis and its impact on Bb growth. Specific Aim 2: will determine the effects of Bb infection-induced changes to the gastrointestinal microbiome on host immune function. To separate effects of Bb infection from those of Bb-induced alterations to the microbiome, we will conduct fecal matter transfer experiments to assess effects on endotoxemia, gut permeability, hyper-IgG induction, T-dependent humoral immunity, and the ability to control early Bb dissemination. In Specific Aim 3 we aim to explore the impact of Bb infection on the host metabolome and how this in turn affect immune system health. This will be done by comprehensively measuring Bb-induced changes to the metabolome and assess these changes for their impact on immune homeostasis and immune system health. Thus, the study aims to pursue an innovative new concept of what may underlie the ineffective immune responses to Bb. Expected results would provide significant mechanistic insights and data in support of future human clinical studies and the development of therapeutic approaches that could reduce the effects of infection on short and long-term health.

NSF Awards · FY 2026 · 2026-04

Non-technical description Every living cell is surrounded by a very thin membrane barrier that keeps most large and water-soluble molecules out of the cell. The membrane protects the cell, but it also makes it hard to deliver useful cargo molecules, such as drugs, into cells. Short molecules called cell penetrating peptides can sometimes carry cargo across this barrier, but most known examples work inefficiently and tend to trap their cargo inside internal compartments where the cargo cannot do its job. Recently, researchers discovered a new class of peptides that behave differently. These peptides can move directly across the cell membrane and deliver cargo molecules with much higher efficiency and without entrapment. The goal of this project is to understand how these unusual direct delivery peptides cross cell membranes and why they work better than earlier examples. The team studies how the peptides interact with the lipids that make up cell membranes and how the chemical complexity of real cell membranes affects the interactions. The team develops laboratory membrane systems that closely mimic natural cell membranes to study the interactions in detail. By uncovering the rules that allow peptides to cross membranes directly, this work helps scientists design new molecules to deliver useful cargos into cells. The project also supports the training of undergraduate and graduate students in interdisciplinary research and shares results through publications and outreach activities that introduce students to the science of cell membranes and biomaterials. Technical description The plasma membrane of a cell prevents most hydrophilic macromolecules from entering the cytosol. Classical cell penetrating peptides such as tat and penetratin can deliver these cargos, but they rely on endocytosis. This pathway is inefficient and often traps the cargo inside intracellular vesicles where they are degraded. Recently discovered direct delivery peptides perform much better and use a different mechanism. These peptides can deliver many kinds of cargo to the cytosol at low concentrations and with high efficiency. Current evidence suggests that they cross the plasma membrane by direct translocation, but the molecular basis of this process is still unclear. The goal of this project is to identify the peptide structural features and peptide–lipid interactions that allow efficient direct plasma membrane translocation. The central hypothesis of this work is that these peptides adopt flexible conformations that promote strong interactions between arginine side chains and lipid headgroups at the membrane surface, along with cooperative interactions involving aromatic residues. To test this idea, the team carries out systematic structure–activity and mechanistic studies that compare classical cell penetrating peptides with direct delivery peptides under the same experimental conditions. Plasma membrane lipids are isolated from plasma membrane–derived vesicles and used to build customizable lipid mixtures that reproduce the chemical complexity of biological membranes. The team measures peptide binding, translocation efficiency, structural dynamics, and peptide–lipid interactions in these systems and relate those properties to delivery activity. These studies define the molecular principles that allow efficient membrane translocation and guide the design of new peptide-based delivery materials that can transport a wide range of cargos into living 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.

NIH Research Projects · FY 2026 · 2026-04

Clonal expansion is a process where latently infected CD4+ T cells proliferate in response to their cognate antigen. It is thought that this process contributes significantly to the size of the HIV reservoir and therefore disrupting this mechanism could have a huge impact on the number of latently infected cells. We observed a significant decline in the number of expanded CD4+ T cell clones in an elite suppressor who received chemoradiation for lung cancer and have shown that we can recapitulate this in vitro by stimulating CD4+ T cells from this patient with a combination of cognate antigen to induce proliferation, and either chemotherapeutic or antiproliferative agents to selectively kill the dividing antigen-specific CD4+ T cells. If successful in other individuals, a two- step process of vaccination of individuals with cognate antigen and short-term treatment with chemotherapeutic or antiproliferative agents may be part of a strategy to reduce the size of the reservoir.