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National Institute of Standards and Technology

The National Institute of Standards and Technology (NIST) is soliciting applications from eligible U.S. public school districts or U.S. accredited private educational institutions nominating middle school science teachers, who have successfully completed the NIST Summer Institute for Middle School Science Teachers (NIST Summer Institute), to participate in the NIST Research Experience for Teachers program (NIST RET or Program). The NIST RET will allow the selected teachers to participate in scientific research with NIST scientists and engineers at the NIST Campus in Gaithersburg, Maryland, that will encourage the teachers to inspire their students to pursue careers in fields of Science, Technology, Engineering, and Mathematics (STEM). The selected teachers will be required to attend the NIST RET during the summer of 2011 (exact dates to be decided by the teachers and scientists).

National Institute of Standards and Technology

The National Institute of Standards and Technology (NIST) is soliciting applications from qualified public school districts or accredited private educational institutions that are teaching students in the areas of Science, Technology, Engineering and Mathematics (STEM) at the middle school level (Grades 6-8). Such schools may offer instruction in general science fields including earth science, physical science, chemistry, physics, and/or biology. NIST will award funding that will support the attendance of middle school teachers in the NIST Summer Institute for Middle School Science Teachers (NIST SI), to be held July 6-19, 2010 to be held at the NIST Gaithersburg, Maryland, campus. The aim of the NIST SI is to increase teachers understanding of the subjects they teach, provide materials and resources to implement what they have learned at NIST in the classroom, enhance their enthusiasm for science, and provide them the opportunity to develop an on-going network with the scientists and engineers at NIST, who would be available for consultation even after the NIST SI has ended. The NIST Summer Institute is a hands-on workshop where middle school science teachers are able to take advantage of resources from the nation s standards and measurement laboratory, the National Institute of Standards and Technology. The workshop will provide teachers with instructional materials and ideas to use in their teaching, and will emphasize the measurement science done at NIST. The aim is to take a selection of the cutting-edge research at NIST and help the teachers translate this through hands-on activities into classroom-based learning modules. In addition to ideas and activities to incorporate into lesson plans, teaching tools are directly provided to allow the teachers to demonstrate to their students the activities that they select from this workshop. The program will provide a world-class opportunity for those teaching our nation's next generation of scientists to learn more about the subjects they teach and the research in those subjects at NIST, and offer a platform from which teachers can inspire their students to pursue STEM careers. Teachers representing successful applicants will be supported via a small stipend, awarded through their respective school district or private educational institution.

New Jersey Department of Education

STEM education initiative grants for NJ to expand science, technology, engineering, and mathematics programs in K-12 and postsecondary institutions.

NCI - National Cancer Institute

Summary: Patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) have limited treatment options and poor survival after relapse. While CAR T cell therapies have transformed the treatment of B-cell cancers, their application in AML has been hindered by the absence of safe, leukemia-specific surface antigens and the high toxicity profile of T cell therapies. Additionally, heterogeneous antigen expression on blasts promotes resistance and escape from therapies targeting a single surface marker. AML blasts, however, are susceptible to natural killer (NK) cell killing as they express stress ligands recognized by NK cell activating receptors. Thus, to overcome the challenges of antigen escape, manufacturing logistics, and toxicity, we have developed a first-in-class, cord blood (CB)-derived, off-the-shelf NK cell therapy engineered to express a T cell receptor (TCR) targeting PRAME, a cancer-testis antigen expressed in most AML and high-risk MDS cases but absent from normal hematopoietic stem cells. These PRAME-TCR/IL-15 NK cells co-express the full CD3 complex for TCR signaling, a costimulatory domain to enhance activation, and secreted IL-15 to improve persistence and metabolic fitness. This platform combines the intrinsic antitumor properties of NK cells with the antigen specificity of T cells. This is the first clinical trial to test a TCRengineered NK cell therapy targeting an intracellular antigen and builds on our prior success with CB-derived CAR NK cells s (NEJM 2020; Nature Medicine 2024). The protocol has received IRB and FDA approval (Protocol 2024-0196, IND 30518), and enrollment is ongoing. We have established a GMP-grade cryopreserved biobank of >30 billion PRAME-TCR/IL-15 NK cells, enabling immediate bedside delivery. Our central hypothesis is that that PRAME-TCR/IL-15 NK cells will show clinical activity with reduced toxicity in AML and that paired immune profiling and CRISPR-based functional genomics will reveal key regulators of therapeutic response and resistance. In Aim 1 we will conduct a Phase I/ II clinical trial to evaluate the safety and efficacy of PRAME-TCR/IL-15 NK cells NK cells in patients with R/R AML and high-risk MDS. In Aim 2 we will perform innovative correlative studies to track the fate and functional dynamics of the adoptively infused engineered TCR-NK cells in vivo, using advanced single-cell proteomic and transcriptomic approaches. In Aim 3, we will apply genome-wide CRISPR knockout screens to identify tumor-intrinsic and NK cell intrinsic regulators of therapy response and resistance, followed by in vitro and in vivo validation of top targets. This study represents a new class of immunotherapy, combining the innate safety, antitumor cytotoxicity and scalability of NK cells with the precision of TCR targeting. If successful, this platform could be extended to other PRAME+ cancers and reshape the landscape of allogeneic immunotherapy. Animal models are required to assess the in vivo persistence, trafficking, antitumor activity and safety of PRAME TCR-engineered NK cells in the physiologic context of disseminated AML. These dynamic interactions between tumor burden, tissue distribution, NK cell expansion and toxicity cannot be adequately modeled in vitro and are necessary to support translation of this therapeutic approach.

NINDS - National Institute of Neurological Disorders and Stroke

Project Summary: Chronic pain, widely considered the United States’ #1 public health crisis, is the most common cause of long-term disability in the world, affecting more than 25 million people in the US and nearly one third of the world’s population overall. Current pharmaceutical treatment options are broadly ineffective and often contribute severe side effects, including anxiety, heart disease, liver disease, and/or addiction. To address the enormous unmet public health challenge of peripherally-mediated chronic pain, novel phenotypic screening tools and new, non-addictive chemical entities that serve as pain therapeutics are urgently needed. Here, we propose a new collaboration that aims to discover novel, non-opioid and non-addictive analgesics from marine microbial resources and advance them to enter the Pain Therapeutics Development Program (PTDP). Our proposal exploits a recently developed phenotypic assay, developed through the HEAL Initiative, that leverages human induced pluripotent stem cell (hiPSC) sensory neurons and glia cultured on multi-well microelectrode arrays (MEAs). This allows long-term and high- content characterization of sensory neuron electrophysiology under baseline (spontaneous) and evoked (thermal and electrical stimulus) conditions. This moderate throughput, pain-physiology-relevant system for hit identification represents a unique approach to compound screening that has yet to be applied to natural product-derived analgesic discovery outside of the preliminary data provided in this proposal. We will employ this unique assay to screen an existing library of purified and structurally characterized marine microbial natural products and extract fraction libraries generated from a diverse and chemically rich culture collection of marine bacteria. We further exploit a new approach called Small Molecule In Situ Resin Capture (SMIRC) to access chemical space that is not available using culture dependent techniques. The hiPSC assay will be used to identify high-priority hits and guide the isolation of active compounds, which will be structurally characterized and tested for toxicity and addiction phenotypes to inform prioritization. A carefully planned workflow, including collaboration with a small biotech company focused on analgesic lead optimization, will maximize the discovery potential of this program.

NIGMS - National Institute of General Medical Sciences

Project Summary My laboratory investigates epigenetic mechanisms in health and disease. In 1R01GM141349-01A1, we proposed to investigate the mechanisms by which the E3-ligase RING1B, a core member of the Polycomb Repressive Complex 1 (PRC1), positively regulates the expression of oncogenic pathways in breast cancer. In 1R01GM146409-01, we proposed to study how the epigenome is remodeled, and genome instability is regulated, by the loss of H3K36me and Polycomb complexes (PRC1/2) in head and neck squamous cell carcinoma (HNSCC). By converting both R01s to a MIRA-R35 under the unifying umbrella of “Non-canonical functions of Polycomb complexes,” we intend to continue working on the aims we proposed in both grants and expand our research program. New research programs include to determine the role of the RING1B paralog RING1A in gene regulation in breast cancer (both in the settings of sensitive and resistance to current therapies) and the identification and characterization of the first set of non-histone substrates of RING1A and RING1B. To address these questions, we will use multiple model systems including new and established breast and HNSCC cellular models, knock-in (KI) and knock-out (KO) cell lines, patient-derived organoids (PDO), xenografts (PDX), and orthotopic xenograft models, biochemistry and mass spectrometry assays. These efforts aim to unravel novel epigenetic mechanisms deregulated in cancer to develop novel targeted therapeutic strategies, encompassing potential combinations with anti-epigenetic compounds. We also propose another original research program aiming to decode the role of novel de novo missense mutations on PRC1 genes that drive neurodevelopmental disorders. This is particularly significant because the prevalence of neurodevelopmental disabilities in children has risen sharply in recent years, while their underlying causes remain largely unknown and insufficiently studied. To address this, we generated the first set of mouse models, along with human and mouse embryonic stem cells, engineered to carry PRC1 variants newly identified by us in individuals with neurodevelopmental disorders. Our research into genetic disorders not only will provide clinical insights but also reveal fundamental mechanisms by which chromatin regulates brain development and neuronal networks underlying cognition. Overall, our program will uncover fundamental mechanisms of gene regulation that profoundly influence cell identity, differentiation, and oncogenesis, while paving the way for precision medicine and enhanced interventions for cancer and developmental disabilities.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY The initiating factor for opioid use disorder often stems from comorbid neuropsychiatric conditions including anxiety, depression, and post-traumatic stress disorder. Experience of extreme or traumatic stress is often the underlying factor responsible for these neuropsychiatric conditions and, thus, investigation into the neural mechanisms by which stress impacts the brain is essential for determining the mechanisms responsible for the initiation of substance use disorders. Our preliminary data demonstrates that stress exposure leads to increased cytokine release and heightened activity of the noradrenergic locus coeruleus (LC), a key region responsible for the integration of stress signaling that projects norepinephrine to numerous downstream brain areas. The prelimbic cortex of the medial prefrontal cortex (PrL) is one such region that receives over 90% of its noradrenergic innervation from the LC and plays a major role in drug seeking and reward-related behaviors. Thus, the overall goal of this project is to establish the circuit mechanisms of stress-related norepinephrine release in the PrL and the role of these projections in oral oxycodone seeking behaviors. These experiments will use cutting edge techniques including chemogenetics, in vivo electrophysiology, and fiber photometry with GRAB sensors to monitor neuronal activity and transmitter release across this circuit in response to stress and drug stimuli. Three main experiments have been designed to address the hypothesis that stress-evoked increases in neuroimmune activity in the LC initiate neuronal activation and downstream NE release to mediate stress- induced drug seeking behavior. First, chemogenetic suppression of neuroimmune activity in the LC will be paired with in vivo electrophysiology during stress to monitor the impact of microglial reactivity on neuronal activity within this region (Aim1, K99). The second experiment will utilize GRABNE sensors in the PrL to determine the time-course of norepinephrine release in response to stress cues. These studies will also use adrenergic receptor antagonists microinjected into the PrL during stress-cue reinstatement to determine the mechanisms by which NE is acting in this region to impact drug seeking behaviors (Aim2, K99). The final experiment will use translationally relevant compounds to determine if the reversal of stress-induced neuroimmune reactivity can prevent the deleterious effects observed as a consequence of stress (Aim3, R00). Taken together, these studies will expand our understanding of the circuit mechanisms responsible for stress-related opioid seeking behaviors and determine the therapeutic potential of clinically available pharmaceuticals all while providing extensive training in innovative preclinical techniques. The combined technical training and career development opportunities supported by this application will facilitate further independent projects designed to address unanswered questions regarding the neural mechanisms responsible for opioid use to develop novel treatment targets for comorbid stress and substance use disorders.

NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases

Project Summary The purpose of this ‘A1 Single-Year NIAMS/NCI R13 Research Conference Grant’ is to host the highest impact scientific and mentoring conference on “Bone: Musculoskeletal Tumor Perspectives’ that will bring together translational and clinical investigators from diverse specialties. Musculoskeletal Tumor Society (MSTS) is the primary host organization that will partner with OREF, ORS, AAOS, and JOR. Musculoskeletal Oncology is a distinct hybrid clinical and research field that requires the solution to 3 distinct problems: ‘Diagnosing’ and ‘Treating’ molecular oncogenesis of MSK tissues and ‘Reconstructing’ afflicted tissue structures to restore limb function. Due to underlying oncological pathophysiology and massive skeletal defects, traditional orthopaedic treatments using trauma or arthroplasty disciplines were associated with high rate of complications. Furthermore, no cross-disciplinary research and mentoring endeavors on bone tumors have not been offered. Many bone and osteoclast-associated molecules were discovered from bone diseases and tumors such as the giant cell tumor of bone. The last AAOS-initiated R13 Conference was in 2017. There is a serious issue of discontinuation of clinician scientists and basic scientists who conduct cross-disciplinary research on bone and reconstruction science from a perspective of musculoskeletal tumors. There is an urgent need to host a R13 conference to offer mentorship for emerging investigators and to develop new collaborations. Our innovative meeting format features sessions addressing challenging clinical problems with plenary overview talks by experts on state-of the art techniques (spatial biology, artificial intelligence, novel signaling & targeted therapies, novel skeletal stem cells, RNA/DNA therapeutics, 3D printed custom device, and mixed reality). We will invite junior surgeon-scientists to present their innovative solutions in mentoring sessions where a panel of established investigators will critique proposed strategies and Specific Aims in a live multi-disciplinary “study section”. ESI selection criteria are based on one-page Specific Aims that summarizes clinical barriers, hypothesis-/technology-driven scientific and clinical investigation plans, and specific needs for mentorship. A meet-the-mentors session will be set up to foster multi-disciplinary collaboration among mentors and emerging surgeon-scientists, engineers, and basic scientists. In order to facilitate networking and matching mentors- mentees, the meeting phone Apps and website will list mentors and participants with well-prepared research ideas (Specific Aims) and other scientific abstracts. Two Specific Aims are Aim 1. Innovative Mentorship for Emerging Clinicians and Scientists; and Aim 2. Dissemination of Cross-Disciplinary New Knowledge and Techniques for New Collaborations and Enhanced Patient Care. A stand-alone R13 conference could be ideal but too costly for meeting space rent, audio/visual services, and support for young investigators. The R13 Conference will be strategically held immediately prior to the 50th MSTS Annual Meeting for cost reduction and improved participation from clinicians, scientists, allied health care workers, and industry R&D staffs.

National Energy Technology Laboratory

The U.S. Department of Energy (DOE) National Energy Technology Laboratory (NETL) intends to issue an Administrative and Legal Requirements Document (ALRD) on behalf of the DOE Office of Fossil Energy and Carbon Management (FECM) and in collaboration with U.S. Environmental Protection Agency (EPA), entitled IRA: Mitigating Emissions from Marginal Conventional Wells. NETL anticipates issuing the ALRD in August 2023 with an application availability period of 30 days. The ALRD will be funded by the Clean Air Act (CAA), as amended by the Inflation Reduction Act (IRA). DOE is partnering with EPA to make funds available to States for the purpose of working with operators to voluntarily and permanently plug marginal conventional wells on non-Federal lands, supporting environmental restoration of the well pad, and enhancing industry s and States capacities to monitor methane and other air pollutants from wells. If released, this ALRD is expected to make available up to $350 million for financial assistance in the form of grants to States via a formula. Note: The revised Notice of Intent (NOI) document (stemming from synopsis/version 5) can be found under the RELATED DOCUMENTS tab.

National Institutes of Health

The purpose of this funding opportunity announcement (FOA) is to encourage the submission of applications for research to enhance animal stem cells as model biological systems. Innovative approaches to isolate, characterize and identify toti-potent and multi-potent stem cells from nonhuman biomedical research animal models, as well as to generate reagents and techniques to characterize and separate those stem cells from other cell types is encouraged. Studies involving human subjects are not allowed under this FOA. Because the nature and scope of the proposed research may vary from application to application, it is anticipated that the size and duration of each award may also vary. The total amount awarded and the number of awards will depend upon the numbers, quality, duration, and costs of the applications received. Mechanism of Support. This FOA will use the NIH Exploratory/Developmental (R21) grant mechanism and runs in parallel with a FOA of identical scientific scope, PA-07-303, that solicits applications under the R01 grant mechanism. Funds Available and Anticipated Number of Awards. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications. Budget and Project Period: The total project period for an application submitted in response to this funding opportunity may not exceed two years. Direct costs are limited to $275,000 over an R21 two-year period, with no more than $200,000 in direct costs allowed in any single year.The R21 is not renewable. Eligible Organizations: Public/State Controlled Institution of Higher Education; Private Institution of Higher Education; Hispanic-serving Institution; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); Alaska Native and Native Hawaiian Serving Institutions; Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education); Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education); Non-domestic (non-U.S.) Entity (Foreign Organization); Small Business; For-Profit Organization (Other than Small Business).

Food and Drug Administration

<p>The purpose of this program is to support new approaches that can be applied to facilitate therapeutic development in ultra-rare pediatric and adult cancers, including molecularly-defined subsets of more common cancers.&nbsp;</p><p><br></p><p>Specific areas of interest include, but are not limited to, the following examples:</p><p>• Development of infrastructure for a coordination network and data repository for patient-level data across institutions and internationally to support drug development and regulatory decision-making for one or more ultra-rare cancers.</p><p>• Investigations to explore opportunities to develop and validate early clinical endpoints and other novel efficacy endpoints for evaluation of treatments for ultra-rare cancers.</p><p>• Development and implementation of a collaborative multi-stakeholder effort to support generation and use of real-world data leveraging a registry framework for use in development of new therapies for pediatric patients with diffuse midline glioma (DMG) (including diffuse intrinsic pontine glioma, DIPG).&nbsp;</p><p>• Innovative approaches to identify new biologically-driven opportunities for clinical development of previously approved drugs or biologics (hereafter referred to as drugs), including drugs for which development has been discontinued, in ultra-rare cancers.</p><p>• Research to develop novel approaches to preserve the availability of drugs for which commercial developers have discontinued adult development that have strong potential in ultra-rare cancers but lack financial incentives for commercial development</p><p>• Development of methods to incorporate use of telemedicine and/or pragmatic trial design elements&nbsp;(e.g., collecting laboratory and/or imaging data from local facilities) for patient assessments to facilitate enrollment of patients with ultra-rare cancers</p><p>• Development of nanoparticle-based delivery approaches for therapeutic nucleic acids targeting onco-fusion transcription factors in metastatic tumor animal models using targeted bioPROTAC degradation or genomic editing strategies. Successful efforts should demonstrate effective delivery and expression in-vivo to tumor cells, and downregulation of the target transcription factor protein while minimizing off-target effects and limiting sequestration of the nanoparticle by the liver, spleen, and lungs.</p><p>• Research to exhaustively characterize the plasma-membrane protein expression (surfaceome) of an ultra-rare cancer and the presumed healthy tissue of origin, as well as the resident-tissue stem cells, by single-cell transcriptomics and proteomics. These studies, and available correlative database analyses, should be designed to identify possible combinatorial signatures of plasma membrane proteins unique to the ultra-rare tumor. Tumors of interest include Sclerosing epithelioid fibrosarcoma and atypical teratoid rhabdoid tumors (ATRT).</p><p><br></p>

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Summary Obesity is characterized by visceral fat accrual and lipid spillover to liver and heart, driven largely by systemic insulin resistance. Key drivers of obesity are excessive feeding and reduced energy expenditure. Consequently, understanding the mechanisms that control feeding and/or energy expenditure will help develop strategies to combat obesity and metabolic diseases. At the whole organismal level, the central nervous system (CNS), in particular the hypothalamus and hindbrain, sense signals of nutrient availability and coordinate energy metabolism. While cell-types in the arcuate and their functions are well-characterized, how different cell-types and neuronal populations in the paraventricular nucleus of the hypothalamus (PVH), a deep-seated region in the hypothalamus, coordinate peripheral energy metabolism remains poorly studied. In particular, it is unclear how the PVH integrates physiological nutrient-related cues to control peripheral energy and lipid metabolism, and how these processes are disrupted to cause obesity and insulin resistance. My studies using brain-wide imaging of c-Fos, a defined neuron activation marker, revealed that dietary triglycerides administered via an oral gavage activates diverse regions across the brain, with greatest activation in discrete regions of the hypothalamus, including the PVH. Comparative bulk-RNA sequencing of multiple regions with the greatest response to lipids revealed Zinc Finger and BTB Domain Containing 16, a transcription factor required for stem cell maintenance and cell differentiation, as a key ubiquitously upregulated gene in response to corn oil gavage, including the PVH. Based on hypothalamic single-nuclei RNA sequencing, and PVH spatial transcriptomics, we reveal that this lipid-driven induction of ZBTB16 expression occurs in a small cluster of a poorly-characterized PVH neurons. On this basis, I hypothesize that these lipid-responsive PVH neurons play a role in regulating systemic lipid metabolism. Consistently, my preliminary studies in a small group of mice revealed that deletion of ZBTB16 in these PVH neurons leads to weight gain and adiposity when compared to controls. Taken together, in this K01 Mentored Research Scientist Career Development Award, I will test the hypothesis that lipid-driven induction of ZBTB16 in these novel PVH neurons facilitates energy expenditure in peripheral fat depots and maintains energy balance; and that sustained high fat diet feeding alters the activity of these neurons to cause obesity. I will test this hypothesis via three specific aims: Aim 1 will characterize the changes that occur in these poorly studied PVH neurons as mice transition from lean to obesity states; Aim 2 will determine the role of ZBTB16 in PVH neurons in the pathophysiology of obesity; while Aim 3 will evaluate the effect of stimulation of these PVH neurons on the reversal of obesity phenotypes. I expect that the completion of these studies will not only reveal novel roles of an uncharacterized neuronal population in combating obesity, but this K01 grant will also serve as a critical mechanism for my career development into an independent neuroscience-focused obesity researcher.

U.S. National Science Foundation

The main goal of the S-STEM program is to enable academically talented, low-income students to pursue successful careers in promising STEM fields. Ultimately, the S-STEM program seeks to increase the number of academically promising low-income students who graduate with an S-STEM eligible degree and contribute to the American innovation economy with their STEM knowledge. Recognizing that financial aid alone cannot increase retention and graduation in STEM, the program provides awards to institutions of higher education (IHEs) not only to fund scholarships, but also to adapt, implement, and study evidence-based curricular and co-curricular[a] activities that have been shown to be effective in supporting recruitment, retention, transfer (if appropriate), student success, academic/career pathways, and graduation in STEM. To be eligible, scholars must be domestic low-income students with academic ability, talent, or potential and demonstrated unmet financial need who are enrolled in an associate, baccalaureate, or graduate degree program in an S-STEM eligible discipline. Proposers must provide an analysis that articulates the characteristics and academic needs of the population of students they are trying to serve. NSF is particularly interested in supporting the attainment of degrees in fields identified as critical needs for the Nation. It is up to the proposer to make a compelling case that such a field serves a critical need in the United States. [a] an activity at a school or college pursued in addition to the normal course of study. S-STEM Eligible Degree Programs Associate of Arts, Associate of Science, Associate of Engineering, and Associate of Applied Science Bachelor of Arts, Bachelor of Science, Bachelor of Engineering and Bachelor of Applied Science Master of Arts, Master of Science, and Master of Engineering Doctoral (Ph.D. or other comparable doctoral degree) S-STEM Eligible Disciplines Disciplinary fields in which research is funded by NSF, including technology fields associated with the S-STEM-eligible disciplines (e.g., biotechnology, chemical technology, engineering technology, information technology, etc.). The following degrees and disciplines areexcluded: Clinical degree programs, including medical degrees, nursing, veterinary medicine, pharmacy, physical therapy, and others not funded by NSF, are ineligible degrees. Programs for STEM teacher certification or licensure currently covered by the Robert Noyce Teacher Scholarship program (NOYCE) are ineligible for S-STEM funding. Business school programs that lead to Bachelor of Arts or Science in Business Administration degrees (BABA/BSBA/BBA) are not eligible for S-STEM funding. Masters and Doctoral degrees in Business Administration are also excluded. Proposers are strongly encouraged to contact Program Officers before submitting a proposal if they have questions concerning degree or disciplinary eligibility. The S-STEM program particularly encourages proposals from 2-year institutions, predominately undergraduate institutions, and urban, suburban, and rural public institutions.

U.S. National Science Foundation

NSF invests in scientific discoveries, technological breakthroughs, and transformative innovations that strengthen economic growth, enhance security, and improve the lives of Americans and people around the world. Our ability to support that mission requires a robust scientific and engineering (S&amp;E) enterprise in the United States that allows scientists to innovate at the frontier. In addition to funding scientists, America needs next-generation scientific instrumentation that allows scientists to pursue new innovations. In many fields, it is critical that this new scientific instrumentation is developed in the United States. In support of this mission, NSF is initiating a pilot emphasis area for its SBIR/STTR programs to invest in startups and small businesses that are specifically developing enabling technologies that include next-generation instrumentation, novel experimental platforms, and other scientific equipment to advance the frontiers of scientific discovery and strengthen the American scientific and engineering enterprise. This encompasses novel instrumentation necessary for the coming era of AI-driven discoveries. This pilot will prioritize investing in the necessary infrastructure to support entirely new fields of scientific discovery, making new technological breakthroughs and transformative applications possible. Through this approach, NSF will continue to lead in propelling the scientific enterprise to new frontiers. This pilot emphasis area for the NSF SBIR/STTR programs funds across enabling technology areas and market sectors in alignment with the above goals; the programs do not solicit specific technologies for the purpose of procuring goods and services for the agency from startups and small businesses. NSF will continue to invest in other deep-tech ventures through the historic NSF SBIR/STTR programs available here. Funding opportunities are available through the NSF SBIR/STTR programs: Phase I, Phase II, Fast-Track, and Supplements. Each company can receive up to $2.0 million for R&amp;D. Separately, NSF welcomes Strategic Breakthrough proposals, upon recommendation from the Program Officer, for Phase II awardees. NSF takes no equity and awardees keep full ownership of their company and intellectual property. Expanding Participation in STEM and Gold Standard Science: NSF prioritizes cutting-edge discovery science and engineering research, advancing technology and innovation, and creating opportunities for all Americans. NSF also expects the highest standards of scientific rigor, integrity and adherence to tenets of Gold Standard Science in proposals, as appropriate for the field of science and research modality.

U.S. National Science Foundation

The NSF STEM K-12 program in the Division of Research on Learning in Formal and Informal Settings (DRL) in the Directorate for STEM Education (EDU) supports fundamental, applied, and translational research that advances STEM teaching and learning and improves understanding of education across the human lifespan and a range of formal and informal settings.

U.S. National Science Foundation

In 2016, the National Science Foundation (NSF) unveiled a set of Big Ideas, 10 bold, long-term research and process ideas that identify areas for future investment at the frontiers of science and engineering (see https://www.nsf.gov/news/special_reports/big_ideas/index.jsp). The Big Ideas represent unique opportunities to position our Nation at the cutting edge of global science and engineering leadership by bringing together diverse disciplinary perspectives to support convergence research. As such, when responding to this solicitation, even though proposals must be submitted to the Directorate for STEM Education (EDU) / Division of Equity for Excellence in STEM (EES), once received, the proposals will be managed by a cross-disciplinary team of NSF Program Directors. The INCLUDESInitiative is a comprehensive, national effort to enhance U.S. leadership in science, technology, engineering, and mathematics (STEM) discovery and innovation, focused on NSF s commitment to ensuring accessibility and inclusivity in STEM fields, as communicated in the NSF Strategic Plan for Fiscal Years (FY) 2022 - 2026. The vision of the INCLUDES Initiative is to catalyze the STEM enterprise to work collaboratively for inclusive change, resulting in a STEM workforce that reflects the Nation s population. More specifically, the INCLUDES Initiative seeks to motivate and accelerate collaborative infrastructure building to sustain systemic change to broaden participation in STEM fields at scale.Significant advancement of the INCLUDES Initiative's goalswill result in a new generation of STEM talent and leadership to secure the Nation s future and long-term economic competitiveness. With this solicitation, NSF offers support for five types of projects that connect and contribute to the National Network: (1) Design and Development Launch Pilots, (2) Collaborative Change Consortia, (3) Alliances, (4) Network Connectors, and (5) Conferences. The INCLUDES National Network is a multifaceted collaboration of agencies, organizations, and individuals working collectively to broaden participation in STEM. The INCLUDES National Network serves as a testbed for designing, implementing, studying, refining, and scaling collaborative change modelsand is composed of: INCLUDES funded projects Other NSF funded projects Subcommittee on Federal Coordination in STEM Education (FC-STEM) agencies Scholars engaged in broadening participation research and evaluation, and Organizations that support the development of talent from all sectors of society to build an inclusive STEM workforce. All INCLUDES funded projects must operationalize five design elements of collaborative infrastructure - (1) shared vision, (2) partnerships, (3) goals and metrics, (4) leadership and communication, and (5) expansion, sustainability, and scale- to create systemic change that broadens participation in STEM.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

PROJECT SUMMARY/ABSTRACT Telomere biology disorders (TBDs) are a group of rare, inherited conditions characterized by critically short telomeres resulting in a wide spectrum of clinical manifestations, including bone marrow failure and cancer predisposition. Therapy options for bone marrow failure in patients with TBDs are limited to androgen therapy and hematopoietic stem cell transplantation, which are associated with significant challenges, toxicities, and variable rates of success. Recent findings emerging from multiple independent studies have established a critical role for the pyrimidine nucleoside deoxythymidine (dT) in human telomere maintenance and have demonstrated that upregulation of nucleoside metabolism by dT supplementation in vitro leads to telomere elongation. Dr. Helen Reed has developed collaborations across Boston Children’s Hospital (BCH) with the goal of answering the following questions: 1) By targeting telomere maintenance can pyrimidine nucleosides serve as a therapy for patients with TBDs? 2) What biologic effects do pyrimidine nucleosides have in vivo among patients with TBDs? To answer these questions, she has proposed an investigator-initiated, single-center phase I clinic trial with the following objectives: 1) Assess the safety and tolerability of enteral nucleoside therapy in patients with TBDs and 2) Investigate the clinical and biologic effects of enteral nucleoside therapy. In addition to evaluating the primary and secondary endpoints of safety/tolerability and changes in peripheral blood counts, respectively, this phase I trial also proposes biologic correlative studies investigating nucleoside therapy’s effect on peripheral blood lymphocyte telomere lengths, bone marrow cellularity, and clonal hematopoiesis. The results of this research will form the basis of future investigations including efficacy trials and mechanistic studies of nucleoside therapy in patients with TBDs. Dr. Reed has completed significant preliminary work toward study activation including protocol development, FDA IND authorization (FDA IND #173750), and BCH IRB approval. Dr. Reed is an Instructor in Pediatrics at Harvard Medical School with appointments in the Division of Hematology/Oncology at Boston Children’s Hospital and Dana-Farber Cancer Institute. Dr. Reed is dedicated to improving the outcomes of patients with telomere biology disorders and other inherited bone marrow failure disorders with the goal of becoming an independent clinical investigator and clinical trialist. While she has a strong track record in clinical research, she requires further training in clinical trial design and conduct in order gain deeper expertise to support the development of future trials in a rare disease space. Her co-mentors, Dr. Akiko Shimamura and Dr. Suneet Agarwal, and her scientific advisory committee bring a considerable wealth of experience in translational research and early phase clinical trial design in hematology/oncology. This mentorship team, along with the dynamic scientific environment at Boston Children’s Hospital, will position Dr. Reed well for a successful, independent career in patient-oriented research in inherited bone marrow failure syndromes.

NIDCD - National Institute on Deafness and Other Communication Disorders

Project Summary Our ability to taste is facilitated by maintenance of different types of cells within taste buds that are specialized to detect diverse taste modalities. Taste bud cells undergo rapid turnover, which likely reflects the harsh environment in which they exist, yet we retain constancy in our taste perception. Previous studies of postmortem tissue using tritiated thymidine or nuclear analogs have reported a proposed average half-life of 8 days for Type II taste bud cells, and 22 days for Type III circumvallate taste bud cells by labeling the proliferating stem cell population. This method allows reporting of population-level lifespan averages for specific cell types but not individual cell variability for specific cell types. Lifespan variability within a specific cell type is likely influenced by both intrinsic factors, such as genetics, and extrinsic factors, such as the environment. These factors may not only shape differences in cell longevity but also influence how taste bud cells are replenished over time in taste buds. The overall hypothesis for this project is that Type II and Type III taste bud cells have distinct lifespans, each with short-lived and long-lived subpopulations, and that cell loss drives differentiation both under normal conditions and after taste bud injury. To test this, longitudinal in vivo two-photon laser scanning microscopy will be used to repeatedly image the same taste buds over time, tracking individual cell populations as cells enter, mature, and disappear from the taste bud. This approach will allow tracking of the full life cycle of individual Type II and Type III taste bud cells, revealing how their lifespans vary and how environmental factors influence their turnover. The goals of this project are: 1) to determine the time it takes for K14+ progenitor cells and Shh+ postmitotic precursor cells to differentiate into Type II and Type III taste bud cells; 2) to determine the lifespan of mature Type II and Type III taste bud cells; and 3) to determine the timing of Shh+ postmitotic precursor cell entry and differentiation into taste buds after taste bud injury. To achieve this, I will integrate sparse cell genetics, time- lapse in vivo imaging, and two-photon laser scanning microscopy, utilizing innovative automated quantification methods for analysis. If our hypotheses are correct, then this would indicate that differences in the time K14+ progenitor cells and Shh+ postmitotic precursor cells spend in early stages may contribute to variability in mature Type II and III taste bud cell lifespans; that subpopulations of taste bud cells exist for specific cell types; and that homeostatic drive regulates cell number differentiation both under normal conditions and after taste bud injury. This is the first step in investigating the regulatory mechanisms that govern taste bud cell turnover and maintain taste perception.

Ohio Department of Education and Workforce

STEM education initiative grants for OH to expand science, technology, engineering, and mathematics programs in K-12 and postsecondary institutions.

NCI - National Cancer Institute

PROJECT SUMMARY/ABSTRACT Acute myeloid leukemia (AML) is a devastating disease with only 30% 5-year overall survival. As a blood cancer, AML appears poised to benefit from the revolution in engineered cellular therapies and bispecific antibodies. However, a lack of disease-specific targets has resulted in significant toxicity and lack of efficacy at clinically tolerable doses. The tumor necrosis superfamily member CD70 has attracted attention as a possible target to overcome these limitations, given its expression on AML and lack of or >20 fold lower expression on all normal tissues. However, current anti-CD70 CAR-Ts have shown only modest efficacy in AML models. Here, my long-term goal is to develop a new therapeutic approach to overcome these hurdles. The core hypotheses of this proposal is that 1) I can use computational engineering to create a best-in-class, naturalligand based CAR-T capable of clearing even CD70-low AML blasts and leukemic stem cells, and in parallel 2) develop a multifunctional anti-CD70 T cell therapy capable of secreting multiple T-cell-engager (TCE) antibodies in the LSC niche. Success here will define new classes of cellular therapy with curative potential in AML. This work may also outline a new therapeutic strategy use across cancers, to eliminate heterogeneous tumor in the microenvironment while sparing normal cells. To achieve these objectives, I have assembled a multidisciplinary mentorship team with complementary expertise, which includes Dr. Arun Wiita (mentor), Dr. Kevin Shannon (co-mentor), and advisory members Dr. Alexander Marson, Dr. Ansuman Satpathy, and Dr. Catherine Smith. My goal is to establish myself as an academic hematologist with a laboratory-based research program dedicated to translating cutting-edge cellular engineering technologies to solve clinically relevant problems in malignant hematology. This proposal outlines a comprehensive 5-year mentored career development plan that will provide me the essential knowledge and scientific training necessary to successfully become an independently-funded investigator. The training plan includes acquiring various new skills in cutting-edge techniques including murine cancer models and single cell biology and analysis interrogating T cell:tumor cell immunology, as well as enhancing skills in bioinformatics and R programming skills. Murine (vertebrate) studies are required as it is well known in the cell therapy field that in vitro assays are not predictive of therapeutic efficacy in human patients. UCSF provides an exceptional research environment, equipped with cutting-edge technologies and a range of leaders across multiple disciplines in addition to those on my advisory panels, in relevant fields including immunology, cellular engineering, and translational leukemia research. UCSF provides state-of-art facilities and world-renowned faculty, including those at Gladstone Institute for Genomic Immunology, UCSF Cell Design Institute (focused on cell engineering), the UCSF Center for Synthetic Immunology, the Living Therapeutics Initiative, and the UCSF Helen Diller Family Comprehensive Cancer Center.

NCI - National Cancer Institute

PROJECT SUMMARY Our overall goal is to develop a human bone marrow organoid culture method that sustains both normal and leukemic hematopoiesis. A historic inability to culture hematopoietic stem cells (HSC), progenitors, and leukemic blasts beyond days to weeks has hindered fundamental investigations and therapeutic development for hematopoietic pathologies. Notably, a complex bone marrow microenvironment vitally sustains HSC and their leukemic derivatives, containing diverse endothelium, mesenchymal stem cells and osteoid, and providing an essential niche during homeostasis and neoplasia. Conceivably, prior culture systems have been limited by insufficient recapitulation of the structurally and cellularly complex bone marrow microenvironmental niche. In response, we developed an air-liquid interface (ALI) primary bone marrow organoid (BMO) system for acute myeloid leukemia (AML) that propagates intact fragments of bone marrow, preserving osteoid, vascular, and mesenchymal niche components in native spatial orientations. When generated from normal bone marrow, BMO maintain hematopoietic stem cells (HSC) and expand progenitors for >60 days (longest examined), support erythroid, myeloid (including neutrophils) and megakaryocyte differentiation, while BMO transplantation rescues lethally irradiated mice. When applied to leukemia, ALI BMO allow ex vivo expansion of human AML blasts from intact fragments of PDX or primary human bone marrow biopsies, preserving histology, surface markers and mutations for >60 days (longest examined), and undergo successful in vivo transplantation. Our proposal responds to PAR-22-242: Bioengineering Research Grants (BRG), that requests “promising tools, methods and techniques”, “design-directed research” and “organoids that closely mimic physiological conditions”. To exploit this broadly enabling leukemia organoid method, Aim 1 conducts BMO-based live imaging of the bone marrow microenvironment in AML BMO during homeostasis and drug treatment to obtain spatially and time-resolved insights into interactions between AML blasts and the bone marrow microenvironment and modulation by therapies. Aim 2 pursues AML BMO as a tool to define and functionally test AML microenvironmental paracrine signals that are evaluated by pharmacologic blockade for effects on leukemic blasts. Lastly, Aim 3 develops human leukemic BMO as a drug evaluation platform, creating human AML BMO from transplanted PDX models and patient core biopsies, and multiplexing for drug testing, which is correlated to therapy effects on conventional short-term cultures, PDX and prospective clinical outcomes. Importantly, Aim 3 develops methods to enable non-expert institutions to receive live or cryopreserved AML PDO, and to create these cultures themselves. We pursue these goals via a synergistic team of the Multi-PIs Calvin Kuo and Kathy Sakamoto, and Co-investigator Ravi Majeti, towards developing a primary human AML organoid method that leverages a fully native bone marrow microenvironment, with application to studies of leukemia pathogenesis, therapy and precision medicine, and broad potential extension to hematologic diseases in general.

Pennsylvania Department of Education

STEM education initiative grants for PA to expand science, technology, engineering, and mathematics programs in K-12 and postsecondary institutions.

National Institutes of Health

-Purpose. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), invites applications to understand how endogenous pancreatic beta cells are made by studying pancreatic development, with the goal of making pancreatic islets in culture, to explore the potential of animal or human stem/progenitor cells (embryonic or adult; if human embryonic, only NIH-approved human embryonic stem cell lines may be used) as a source for making pancreatic islets, and to determine the basic mechanisms underlying beta cell regeneration in the adult as a basis for producing new cellular therapies for diabetes. This Funding Opportunity Announcement (FOA) is intended to stimulate the application of advances made in developmental biology, stem cell biology, and diabetes to develop new strategies for diabetes therapy, either through cell replacement or regeneration. This FOA is intended to intensify investigator-initiated research, to attract new investigators to the field, and to encourage interdisciplinary approaches to research in this area. -Mechanism of Support. This FOA will utilize the NIH Research Project Grant (R01) award mechanism. -Funds Available and Anticipated Number of Awards. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications received.

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary/Abstract This proposed research project focuses on understanding the pathogenesis of papillomavirus infection in WHIM syndrome and how one can use the mechanisms to develop curative treatment to alleviate papillomavirus infection in WHIM syndrome. The proposed studies will form the foundation for a future research program that focuses on investigating underlying mechanisms of papillomavirus pathogenesis in WHIM and developing curative treatment for them to alleviate papillomavirus-related malignancies. Research: Mouse papillomavirus (MmuPV1) models high-risk human papillomavirus (HPV) infection and associated cancers in mice. This project will use MmuPV1 and a WHIM mutation knock-in mice to understand keratinocyte-intrinsic mechanism of WHIM mutation contributing to papillomavirus pathogenesis, as well as to test whether reversing leukopenia caused by the mutation will clear infection. To determine if rescuing leukopenia is sufficient to clear pre-existing infection, CRISPER/Cas9 will be used to inactivate WHIM allele in hematopoietic stem cells and test if edited hematopoietic stem cell transfer can cure or slow down papillomavirus-induced disease in infected unconditioned WHIM hosts. MmuPV1 and WHIM mutant mice become powerful pre-clinical disease model for WHIM patients and can provide informative data guiding future clinical testing. In addition to pre-clinical testing, this model will also be used to answer whether there is crosstalk between myeloid cells and lymphoid cells that are contributing to infection clearance. This question has been raised from a reported case of chromothriptic cure of WHIM syndrome where the patient spontaneously cleared warts with only recovered myeloid cell count while remained lymphopenia. It is hypothesized that mutation corrected myeloid cells can interact with lymphoid cells bearing WHIM mutation, recruiting them to infected sites to overcome lymphoid cell shortage to clear viral infection. In addition to immune cells, this project also aims to understand how WHIM mutation contributes to papillomavirus life cycle in infected keratinocytes. This project will use in vitro culture of primary mouse keratinocytes derived from WHIM mice and investigate how WHIM mutation affects newly infected MmuPV1 entry, maintenance and amplification. Drugs targeting affected pathways will be tested in vivo to determine if current approved drug for WHIM syndrome is sufficient to treat papillomavirus-related malignancies. The data generated by proposed studies will provide insights into how current CXCR4 inhibitor works, and help design strategies to cure papillomavirus-related malignancies, which is a significant cause of fatality in WHIM syndrome.