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Department of Defense

National Defense Education Program (NDEP) Science, Technology, Engineering, and Mathematics (STEM) Consortia Request for Information (RFI) for the Office of the Under Secretary of Defense (Research & Engineering)

National Grid Foundation

Supports energy affordability, workforce development, STEM education, and environmental sustainability in National Grid service areas.

NASA Headquarters

OPPORTUNITY FOR THE USE OF THE INTERNATIONAL SPACE STATION BY DOMESTIC ENTITIES OTHER THAN U.S. FEDERAL GOVERNMENT AGENCIES 1.0 INTRODUCTION AND BACKGROUND The National Aeronautics and Space Administration (NASA) is operating a share of the United States accommodations on the International Space Station (ISS) as a national laboratory in accordance with Section 507 of the NASA Authorization Act of 2005 (P.L. 109-155) and to seek to increase the utilization of the ISS by other federal entities and the private sector. To facilitate and increase such utilization of the ISS, NASA is providing access to the ISS for the conduct of basic and applied research, technology development and industrial processing (collectively, R&D) to U.S. federal, state and local government entities, and to U.S. private entities (including, but not limited to, commercial firms, non-profit entities, and academic institutions) as part of the national laboratory. In preparation for the ISS post-assembly phase and during the post-assembly complete phase, NASA is seeking proposals from domestic entities other than U.S. federal government agencies for the conduct of R&D activities on the ISS as a national laboratory. NASA anticipates using its authority to enter into Space Act Agreements to support national laboratory activities, including providing necessary access to NASA facilities, personnel and technical information, however, there will be no provision of funds in connection with this opportunity. Respondents will be responsible for financing their own activities. Participation in this National Lab Opportunity will be contingent upon selection by NASA and negotiation of an appropriate Agreement between NASA and the proposer. Proposed activities should involve R&D, including, but not limited to, life sciences, sensors, communication equipment, engineering testbeds, spacecraft design and testing, or education and should demonstrate potential benefit to the public, such as development of future products and services contributing to U.S. industrial capacity and economic growth or improving STEM education. This opportunity is not exclusive; NASA, at its discretion, may negotiate with other parties for access to ISS under this opportunity. Response Date: This announcement is open through December 31, 2014. NASA will engage in ongoing review of proposals as received prior to the Response Date of December 31, 2014. NASA reserves the right to amend or withdraw this Announcement at any time prior to the Response Date. NASA will not issue paper copies of this Announcement. NASA reserves the right to select for Space Act Agreement negotiations all, some, or none of the proposals submitted in response to this Announcement. NASA provides no funding for reimbursement of proposal development costs. Material submitted in response to this Announcement will not be returned. It is the policy of NASA to safeguard all proposals as confidential and privileged information, as provided by law. NASA will not, without permission of the proposers, use the proposal contents for other than evaluation purposes. It is not NASA's intent to publicly disclose proprietary information obtained during this solicitation. To the full extent that it is protected pursuant to the Freedom of Information Act and other laws and regulations, information identified by a respondent as "Proprietary or Confidential" will be kept confidential. NASA may use contractor support personnel to assist in providing expertise regarding proposals. Any support contractor involved in the evaluation process shall be free of conflicts of interest, will be bound by appropriate non-disclosure agreements to protect proprietary and competition sensitive information. By submitting a proposal under this Announcement, the proposer is deemed to have consented to release of data in its proposal to NASA contractors supporting evaluation of proposals. 2.0 GENERAL INFORMATION Agency Name: NASA (National Aeronautics and Space Administration) Opportunity Title: Opportunity for the use of the International Space Station by Domestic Entities Other than U.S. Federal Government Agencies Response Date: Electronic Proposals must be received by December 31, 2014 at 4:30 P.M. EST via email to jason.c.crusan@nasa.gov. Proposals may be submitted at any time before the response date. Points of Contact: If you have any questions concerning this opportunity please contact: Marybeth Edeen Manager, ISS National Lab Office Telephone: 281-483-9122 Fax: 281-244-8292 Email: marybeth.a.edeen@nasa.gov Jason Crusan SOMD Agreement Manager 202-358-0635 202-358-3530 jason.crusan@nasa.gov Instrument Type(s): It is anticipated that awards under this Opportunity will be in the form of Space Act Agreements, executed under the authority of 42 U.S.C. 2473(c)(5). Selection Recommendation Committee: Government personnel from NASA, other Federal agencies, and NASA contractors may participate in the evaluation of proposals. All contractor personnel participating in the evaluation will be bound by conflict of interest provisions and appropriate non-disclosure requirements to protect proprietary information. Selection Notification Date: Selection for negotiations is anticipated to be within 60 days of receiving a proposal. Submission Instructions: All Proposals under this Announcement must be emailed to jason.c.crusan@nasa.gov. Paper submissions will not be reviewed. Proposals may be submitted at any time before the Response Date. You are encouraged to submit as early as practicable prior to the Response Date. Proposals received by the Government after the Response Date will not be accepted. If a proposer is concerned about information security during transmission NASA has the ability to accept secure transmission. Contact the Point of Contact for secure transmission requirements. Files can be submitted in MS Word, PDF, or RTF. 3.0 ELIGIBILITY INFORMATION All categories of domestic entities other than U.S. federal government agencies are eligible to submit proposals in response to this Announcement. NASA will not consider proposals which do not include a domestic entity as the lead proposer. 4.0 PROPOSAL EVALUATION AND SELECTION 4.1 Evaluation and Selection Process All proposals will be initially screened to determine their compliance to the eligibility (section 3.0) and proposal instructions (section 5.0) of this Announcement. Proposals that do not comply may be declared noncompliant and rejected without further review. A submission compliance checklist is provided in section 5.0. This checklist provides proposers a list of the items that NASA will check for compliance before releasing a proposal for evaluation. Proposals deemed in compliance with this Announcement will be assessed against the evaluation criteria outlined in Section 4.2 by the Selection Recommendation Committee. Proposed collaborators should be aware that during the evaluation and selection process, NASA may request clarification of a specific point or points in a proposal. Such a request and the proposed collaborator's response shall be in writing. NASA reserves the right to suggest collaboration between proposers where it will enhance the effort, in which case proposers will be given the opportunity to accept or decline participation with other proposers prior to selection. The Selection Recommendation Committee members will conduct independent assessments of the proposals according to evaluation criteria outlined in Section 4.2. 4.2 Evaluation Criteria The evaluation factors below are of equal weighting during evaluation. Factor 1: Approach to Proposed Effort: The overall merit, rationale, feasibility, and suitability of the proposed effort or concept and its relevance to R&D that access to the ISS provides. Highest priority will be placed on an approach or concept that will create substantial increases in the current state-of-the-art. Describe how the proposer proposes to receive resulting data and/or samples from orbit. Factor 2: Level of Benefit to the Public: The proposed effort or concept's anticipated benefit to the public, in terms such as development of future products and services, and contribution to U.S. industrial capacity and/or economic growth. Factor 3: Level of Financial Commitment and Business Plan: The description of the level of financial commitments supporting the proposed efforts, including any third party financing required. Include a brief business plan for the proposed efforts or describe how the proposed efforts contribute to existing business plans. Identify the non-U.S. Government market potential for the R&D efforts. The proposed space activity is essential to product research, development, or processing, and is targeted to an addressable market. A roadmap exists; it includes the essential activities to bring the product to market beyond the development space activities. In addition, describe all cargo to be transported between Earth and the ISS that your proposed efforts require and how your business plan addresses meeting those requirements including any sample return and disposition of the on-orbit equipment/payloads. In addition, NASA reserves the right to assess information outside the proposal as it relates to the factors listed above. 4.3 Selection Factors As described in Section 4.1, the results of the proposal evaluations based on the criteria above and the subsequent Selection Recommendation Committee deliberations will be considered in the selection process. The Selection Recommendation Committee may take into account a variety of programmatic factors in deciding whether or not to select any proposals, including, but not limited to, available on-orbit resources, and compatibility to the ISS. The Selection Authority shall be the Associate Administrator for Space Operations. The Selection Authority will make the final selection of those approved for this opportunity after the completion of negotiations, depending on the outcome of the negotiations. 4.4 Selection Notification NASA will notify all proposed collaborators of the results of the evaluation and selection process. Selection does not guarantee a launch opportunity. Selection does guarantee NASA will provide the on orbit resources and trained crew to perform the experiment once it is on board. After the completion of the evaluation and selection process, NASA will begin negotiations with the selected proposer(s). The purpose of the negotiations is to define the terms and conditions of the Agreement supporting the participation of the proposers and to align the selected proposals with the anticipated on-orbit resource availability. All work will commence after the parties execute the Space Act Agreement. 5.0 PROPOSAL INSTRUCTIONS Proposals must comply with the following requirements. Page Limitations Proposal Section - Total Pages Proposal Cover Page - 1 Proposal Title Page - 1 Points of Contact - 1 Proposal Abstract - 750 words Proposal Detail - 10 Appendix Resumes - No Page Limit Additional Documentation - No Page Limit Pages in excess of the page limitations for each section will not be evaluated. A page is defined as one (1) sheet 8 x 11 inches using a minimum of 12-point font size for text and 8-point for graphs. There is no limit on appendix documentation. The intent is to allow proposals to include current documentation in its current format without having to alter any documents. The proposal must include the following sections, in this order: Proposal Cover Page: Solicited Proposal Application - Title of Announcement and Proposal Contact Information. An optional graphic image may be included. Proposal Title Page, with Notice of Restriction on Use and Disclosure of Proposal Information, if any. Points of Contact: List contact information for all Points of Contact including a Technical Point of Contact. Provide: a. Name b. Title c. Address d. Phone and Fax e. Email Proposal Abstract: Executive summary describing the prominent and distinguishing features of the proposal. Proposal Detail: The proposal shall contain sufficient information to enable reviewers to make informed judgments to assess the three criteria of the proposed effort. Proposal Appendix: * Resumes o Resumes may be included for key personnel. In general, resumes should be limited to no more than 1-2 pages each. * Additional documentation Include any documentation in the appendix that validates or supports the proposal Compliance checklist and required documents o The proposer is a domestic entity other than U.S. federal government agency o Proposal includes demonstration of the overall merit, rationale, feasibility, and suitability that access to the ISS provides o Proposal includes a description of the level of benefit to the public o Proposal includes a description of the level of financial commitment and business plan o Proposal includes a schedule for remaining development required before flight o Proposal includes a management/ project plan for remaining development o Proposal includes funding commitment letters demonstrating sufficient financial support for remaining development or financial milestones required to complete development

NINDS - National Institute of Neurological Disorders and Stroke

SUMMARY The National Neurotrauma Society (NNS) is committed to the promotion of neurotrauma research by enhancing communication, providing a forum for scientific exchange, and increasing national and international support for neurotrauma research and clinical advances. The society holds an Annual Symposium to provide a forum for researchers, clinicians, and trainees from around the world to meet and discuss the latest breakthroughs in traumatic brain injury (TBI) and spinal cord injury (SCI) research. The 43rd Annual Neurotrauma Symposium, jointly sponsored by the NNS and the American Association of Neurological Surgeons/Congress of Neurological Surgeons (AANS/CNS) Joint Section on Neurotrauma and Critical Care will be held in Milwaukee, WI, June 14- 17, 2026. Two of the historic strengths of the Neurotrauma Community are training/mentoring and collaboration. One of our primary goals is to promote and retain our top trainees. Another key goal is improving outcomes in our neurotrauma patients, which is best addressed by working together, whether locally or in a multi-institutional setting, and to continue to push our field forward. To this end, the theme for the 2026 NNS Symposium is “Brainstorming for Breakthroughs.” NNS Symposia have a history of bringing together scientists, clinicians and healthcare providers, trainees, and individuals with lived TBI or SCI experience who are dedicated to the study of neurotrauma to translate knowledge generated by research into improved patient care. The centerpieces of the Symposium are our travel awards, poster competition, data blitz oral presentations, workshops and activities designed and supported by the Training, Education and Mentoring (TEAM) Committee that foster participation and active engagement of trainees and young investigators. NIH funding for previous NNS Symposia has been focused on these trainee opportunities and provided invaluable support to reach graduate students, postdoctoral researchers, residents, and young investigators. This application seeks funding to support 40 pre-and-postdoctoral trainees to present their ongoing work, attend scientific sessions, and to network with peers and faculty. In addition, we request support for our Local Scholars program that seeks to attract new undergraduate students to the Society by supporting 30 undergraduate trainees from local host-city Universities with a background in STEM and neuroscience. Our aims are to; 1) provide a strong scientific program focused on “Brainstorming for Breakthroughs,” highlighting recent transformative discoveries in neurotrauma research, and 2) enhance training, education and mentorship of trainees and early-career faculty. This will include trainee development through workshops, mentor:mentee events, breakout sessions, poster competition, Local Scholars program and platform presentations.

U.S. National Science Foundation

The U.S. NSF Directorate for Technology, Innovation and Partnerships (NSF TIP) partners across sectors to advance three primary focus areas accelerating technology translation and development, fostering regional innovation and economic growth, and preparing the American workforce for future high-wage jobs in STEM fields. The translation of research to practice ensures that the insights and innovations developed through scientific study and experimentation have tangible, positive impacts for the Nation. These impacts include improving the quality of life, promoting economic and job growth, ensuring national security, and maintaining global competitiveness. Indeed, scientific and engineering breakthroughs have the potential to address critical societal challenges in industries such as aerospace, agriculture, communications, education, energy, healthcare, national security, and transportation but the translation of discoveries and innovations from the laboratory to society often takes many forms including non-linear pathways. The NSF TTP program was developed with several goals in mind: To identify and support use-inspired research and translational activities enabling a continuum from foundational research to practice; To develop partnerships and collaborations between institutions of higher education and other entities (e.g., industry, state/local/national government agencies, philanthropies, open-source ecosystems, for-benefit, for-profit and non-profit organizations, international organizations, etc.); To promote and advance the education and training of students and postdoctoral researchers, encouraging the participation of all Americans in STEM including innovation and entrepreneurship; and To identify future customer needs and opportunities and bring these to the forefront in the conduct of use-inspired research and translational activities. The NSF TTP program offers three tracks that represent different starting points or stages in moving discoveries and innovations from the laboratory to practice: NSF TTP-Explore (NSF TTP-E) is a pilot track that is likely to be the first step for researchers seeking to translate their basic research to practice. To be eligible for the NSF TTP-E track, proposers must have an active, eligible, NSF research award (see Eligibility Information for further details). TTP-E is designed to encourage current, eligible NSF awardees to intentionally pursue applications of their research with the potential for societal impact. The NSF TTP-E track provides the opportunity to obtain an extension of the initial award period of a current NSF award for up to two years in order to offer investigators an opportunity to explore adventurous, high-risk, use-inspired research and initial translational activities as the starting point for translation that was not covered by the original research award. NSF TTP-Translate (NSF TTP-T) starts with use-inspired research and initial translational activities and further matures the idea(s), iterates and improves the solution(s), and lowers the barrier(s) to effective translation of research from lab to practice. NSF TTP-Partner (NSF TTP-P) supports translational efforts that demand one or more partnerships for technology development and deployment. Here, strategic partnerships with stakeholders beyond U.S. institutions of higher education are essential ingredients for success and may include industry partners, government entities at all levels, philanthropies, international organizations, or other groups associated with large scale productization and distribution. The NSF TTP-P track requires an NSF-Catalyzed Partnership with an organization that will assist in the translation to practice. In addition to the Principal Investigator (PI), NSF TTP-P proposals must include a co-PI or Senior/Key Personnel who is a member or employee of the NSF-Catalyzed Partner. Partnerships with U.S. institutions of higher education are valued, but NSF TTP strongly prioritizes NSF-Catalyzed Partnerships that are able to help bring the product, process, or service to the market, potentially through licensing agreements, startup or small business formation, incorporation into an existing open-source ecosystem, development into standards setting arrangements, etc.

National Aeronautics and Space Administration

National Space Grant College and Fellowship Program - Opportunities in NASA STEM FY 2020 – 2024

National Aeronautics and Space Administration

This Cooperative Agreement Notice is a multi-year award thataims to contribute to NASA s mission, Office of STEM Education priorities,Co-STEM goals, Mission Directorate collaborations, and state based needs. The multi-year award will be available to allSpace Grant Consortia who will work with the Office of STEM Engagement tofulfill these objectives. Through thecombined efforts of the Space Grant Consortia, this program will 1) enablecontributions to NASA s work, 2) build a diverse, skilled future workforce, and3) strengthen understanding of STEM through powerful connections to NASA. The program will focus on providingopportunities for students to engage with NASA s aeronautics, space, andscience people, content, and facilities in support of a diverse future NASA andaerospace industry workforce, as well as, providingopportunities for students to contribute to NASA s aeronautics, space, andscience missions and work in exploration and discovery through MissionDirectorate collaborations. Everyinstitution that intends to submit a proposal to this NRA, including theproposed prime award or any partner whether an education institution, and otherorganizations that will serve as sub-awardees or contractors, must be registered in NSPIRES. Electronicsubmission of proposals is required by the due date and must be submitted byan authorized official of the proposing organization. Such registrationmust identify the authorized organizational representative(s) who will submitthe electronic proposal. All principal investigators and other participants(e.g. co-investigators) must be registered in NSPIRES regardless of submissionsystem. Potential proposers and proposing organizations are urged to accessthe system(s) well in advance of the proposal due date(s) of interest tofamiliarize themselves with its structure and enter the requested information.Electronic proposals may be submitted via the NASA proposal data systemNSPIRES. Additional programmatic information for this NRAmay develop before the proposal due date. If so, such information will be addedas a Frequently Asked Question (FAQ) or formal amendment to this NRA and postedon http://nspires.nasaprs.com. It is the proposer s responsibility to regularly check NSPIRESfor updates to this NRA. P oint of Contact Name: Erica J. Alston Title: Deputy Space GrantProgram Manager Phone: 757-864-7247 E-mail: SGCFP@nasaprs.com

U.S. National Science Foundation

This program aims to establish a national network of learning environments and resources for science, technology, engineering, and mathematics (STEM) education at all levels. The program has four tracks: Pathways projects are expected to provide stewardship for the content and services needed by major communities of learners; Pathways II projects are expected to move beyond the major stewardship goals and use Stage II support to ensure the expansion and stability of an original Pathways effort; Services projects are expected to develop services that support users and resource collection providers by enhancing the impact, efficiency, and value of the NSDL network; and Targeted Research will focus on investigating the educational impact of networked digital resources. The existing NSDL Resource Center will provide collaboration assistance across all projects; undertake strategic partnership development on behalf of projects particularly with respect to non-academic entities; coordinate and, in some cases, perform thematic research and evaluation studies related to the program; synthesize findings across the portfolio; and disseminate findings of the accomplishments of the NSDL program. The NSDL Technical Network Services project operates NSDL's infrastructure and NSDL.org; provides technical support for NSDL tools, services, and collections management; supports Pathways and other NSDL projects in contributing resources and collections to NSDL; and engages the NSDL community in identifying priorities for services developments. In FY2010, the program will accept proposals for large grants in 1) the Pathways track, 2) Pathways - II, 3) specific sub-tracks of Services, and 4) Targeted Research. In all tracks, the program will also accept proposals for small grants that extend or enhance results from existing services, collections, or targeted research activity to enlarge the user audience for the NSDL network or improve capabilities for the user.Technology-intensive projects that explore specific topics that have immediate applicability to collections, services, and other aspects of the development of the NSDL network should seek small grant support under the Services section of the program. In addition the program particularly encourages proposals for small grants from institutions and organizations new to NSDL that look to establish partnerships with existing Pathways project activities.

NC Department of Public Instruction

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

Washington Headquarters Services

This is an open NFO, applicants may apply to this posting or subsequent amendments for specific STEM activities. See the Related Documents tab for the full NFO, and amendments announcing new funding opportunities. The Department of War (DoW) Office of the Under Secretary of War for Research and Engineering (OUSW(R&E)) seeks innovative applications on mechanisms to implement and research the effectiveness of STEM education, outreach, and/or workforce initiative programs, here onto referred as STEM activities. In response to this NFO, the Department intends to release amendments and solicitations, such as Industry Days, Opportunity Days, etc., detailing funding opportunities through award(s) in STEM activities. These activities include, but are not limited to: STEM Education and Outreach Support for STEM Education at Two-Year Institutions/Community Colleges (2YI/CCs) Manufacturing Engineering Education Program Education and Workforce Development aligned to the DoW Critical Technology Areas STEM Scholarship Programs Strategic Partnerships Program Evaluations, Assessments, Data Analytics and Visualizations Other NDEP Congressional Initiatives and Programs As funding becomes available, NFO amendments or Industry Day/Opportunity Day announcements detailing opening and closing dates for topics of interest will be posted. In response, applicants may be asked for a mandatory white paper submission, emailed to osw.ndep.dowstem@mail.mil. Refer to the amendment for formatting the email subject line. Use of the white paper is intended to determine which efforts are of merit preparatory to submission of a full application as described in Section IV. Applicants will be selected from the white paper submissions to be invited by the Government via email to submit a full application on Grants.gov for evaluation and possible award consideration. White papers that fail to address the areas listed in the Program Description of the NFO amendment or Industry Day/Opportunity Day announcement will not be evaluated and will not receive an invitation to submit a full technical application. White paper submissions will only be accepted in response to active NFO amendments or Industry Day/Opportunity Day announcements. In addition to the submission requirements outlined in Section IV, all responses should address items in the specific NFO amendment or Industry Day/Opportunity Day announcement.

National Institutes of Health

The NEI uses UG1 cooperative agreement awards to support investigator-initiated clinical vision research projects, including multi-center clinical trials, human gene-transfer, stem cell therapy trials, epidemiological studies, and other studies that are complex, high resource, or that require increased oversight due to elevated safety considerations.These collaborative clinical vision research projects would address chronic diseases across the lifespan through research on the burden of eye and vision conditions, their causes, diagnoses, prevention, treatment, and rehabilitation. These projects are multifaceted and of high public health significance, requiring careful oversight and monitoring by National Institutes of Health (NIH) staff. The intent of this funding opportunity announcement is to provide a collaborative framework for the following components: Chair's Grant, Coordinating Center, and Resource Center(s).

National Institutes of Health

<p>The NEI uses UG1 cooperative agreement awards to support investigator-initiated clinical vision research projects, including multi-center clinical trials, human gene-transfer, stem cell therapy trials, epidemiological studies, and other studies that are complex, high resource, or that require increased oversight due to elevated safety considerations.</p><p>These collaborative clinical vision research projects would address chronic diseases across the lifespan through research on the burden of eye and vision conditions, their causes, diagnoses, prevention, treatment, and rehabilitation. &nbsp;These projects are multifaceted and of high public health significance, requiring careful oversight and monitoring by National Institutes of Health (NIH) staff.&nbsp;&nbsp;</p><p>The intent of this funding opportunity announcement is to provide a collaborative framework for the following components: Chair's Grant, Coordinating Center, and Resource Center(s).</p>

NIDA - National Institute on Drug Abuse

Individuals with cocaine use disorder frequently experience competing motivations that simultaneously push them to seek out cocaine and push them to not engage in such behavior. Such competing motivations may stem from both a desire for the rewarding nature of the drug and a desire to avoid adverse consequences associated with the drug use. However, the neural systems that mediate decision making under such circumstances are not well understood. The long-term goal of our laboratory is to elucidate the neural systems and networks that underlie the competing motivations for cocaine-seeking behavior, using rat models of cocaine seeking. Our prior work has identified important corticolimbic circuitry involved in the extinction of cocaine seeking after drug self-administration, but such behavioral procedures do not create a simultaneous “in-the-moment” motivational competition. Therefore, for the present proposal, we developed a novel behavioral paradigm in which rats undergo trial-based cocaine self-administration. At the beginning of each trial, a discriminative stimulus (DS) indicates whether an active lever press will produce cocaine or, alternatively, a footshock. After rats acquire this task, they then undergo “competition” tests that consist of DS- cocaine trials, DS-shock trials, and competition trials in which both DS’s and both consequences occur. These procedures will enable us to probe the neural circuits that mediate the decision of whether to engage in cocaine seeking despite a negative consequence (i.e., the competition trials). Prior work has identified the insular cortex as a critical region for drug craving, yet the studies on this region within rodent models, including our own, have been somewhat limited and frequently conflicting. Other evidence reports that the insular cortex is important for decision making “under risk”, suggesting that the previous work examining this region in cocaine seeking did not use the best behavioral models for elucidating its function. Therefore, the present proposal will use our newly developed competing motivations cocaine-seeking model to examine the neural circuits centered on the anterior portion of the insular cortex. In particular, our studies will use temporally precise manipulations of specific inputs to this region and outputs from this region during this task to identify those pathways’ roles during different aspects of the task. Moreover, we will also use neural measures with strong temporal resolution to relate activity in these pathways as well as across a larger network of brain regions to develop a more sophisticated understanding of how these regions communicate during the task. Thus, the proposed studies will provide converging lines of evidence for how these circuits and networks promote and inhibit cocaine seeking depending on the specific circumstances facing the animal.

NHLBI - National Heart Lung and Blood Institute

Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of death in patients with epilepsy. SUDEP mechanisms are not understood, although there is evidence to implicate apnea, autonomic dysfunction, and cardiac arrhythmias. Genes encoding voltage-gated sodium channel subunits are high SUDEP risk genes. Loss- of-function variants in SCN1A are linked to the Developmental and Epileptic Encephalopathy (DEE) Dravet syndrome (DS). Importantly, SCN1A is expressed in both heart and brain. Thus, we proposed that cardiac arrhythmias contribute to the mechanism of SUDEP in channelopathy-linked genetic epilepsies. We have shown evidence for altered cardiac myocyte sodium current density, calcium handling, and action potentials (APs), as well as cardiac arrhythmias in mouse models of DEE. We also showed that induced pluripotent stem cell (iPSC)- derived cardiac myocytes derived from DS patients have substrates for arrhythmias. DS patients also often display disordered breathing, suggesting dysfunctional neural control of respiration may underly SUDEP risk. Importantly, no mouse or iPSC model can completely replicate the human DS phenotype. Because mouse cardiac APs are very different from humans, we used human iPSC-cardiac myocyte models to investigate cell autonomous effects of SCN1A haploinsufficiency, however, cells in 2-dimensional culture cannot replicate complex cardiac tissues, cardiovascular changes, or cardiac autonomic innervation. From the control of breathing standpoint, mouse metabolic adaptability makes them more resistant to hypoxia and prolonged apneas than humans. Thus, we developed a transgenic rabbit Scn1a DS model because rabbits more closely replicate human cardiac and respiratory physiology than mice and, unlike iPSCs, provide a complete organism to translate to the clinical setting. The goal of this proposal is to use DS rabbits to test the hypothesis that Scn1a haploinsufficiency results in altered cardiac and brainstem excitability in addition to generalized seizures, leading to cardiac arrhythmia, altered heart rate variability (HRV), and impaired respiratory pattern generation in the brainstem. We will test our hypothesis by addressing three Aims: 1. To determine whether DS rabbits have cardiac arrhythmias and altered HRV in addition to seizures and to determine whether acutely isolated ventricular and atrial cardiac myocytes have altered excitability. 2. To determine whether DS rabbits have altered regulation of respiration, including changes in the pattern of respiratory motor output, altered patterns of dorsolateral pontine respiratory-related neuronal activity in an intact pontomedullary respiratory circuit, and altered excitability of and GABAergic synaptic transmission onto brainstem dorsolateral pontine neurons. 3. To determine whether intracerebroventricular administration of a TANGO antisense oligonucleotide targeting Scn1a haploinsufficiency can alter brainstem respiratory-related neuronal activity, HRV, or cardiac arrhythmias secondary to autonomic dysfunction in DS rabbits.

NEI - National Eye Institute

SUMMARY/ABSTRACT Neuro-epithelial interactions in corneal disease and repair, Elmira Jalilian (PI) Diabetes mellitus (DM) is a critical global health issue currently affecting 415 million adults and projected to exceed 640 million by 2040. Diabetic corneal neuropathy, defined by progressive nerve fiber loss in the cornea, occurs in approximately 50% of patients with DM. If these patients experience corneal damage, the regenerated corneal epithelium fails to recover full functionality, leading to further corneal complications. The reduced nerve density and impaired functionality of the remaining nerve fibers leads to disruption of corneal epithelial homeostasis (CEH) and the hindering of reparative processes essential for preserving corneal integrity. A key mechanism regulating CEH and repair is the interaction between corneal epithelial cells (CECs) and corneal nerves (the V1 ophthalmic branch of trigeminal nerves or TgV1s). Despite the recognized role of TgV1s in regulating ocular surface integrity through neurotrophic factors, these factors have not been able to fully explain the neuronal contribution to CEH and repair. In the field of ocular biology, there is growing interest in extracellular vesicles (EVs) as novel mediators of cell-cell communication. While the majority of EV-related research in corneal biology has centered on the therapeutic potential of mesenchymal stem cell (MSC)-derived EVs, there are few studies probing the role of cell-type-specific (CTS) EVs in regulating corneal health and disease. Our preliminary data demonstrated that healthy TgV1s secrete functional EVs. When these TgV1 EVs were internalized by CECs, the expression of proteins involved in proliferation, migration, and cell-cell adhesion were increased in vitro, and sequencing data from TgV1 EV-treated CECs showed a uniquely modulated transcriptional program compared with either untreated CECs or MSC EV-treated CECs. In vivo, TgV1 EV-treated corneas exhibited enhanced epithelial cell adhesion, barrier integrity, greater epithelial thickness, more uniform morphology, and stronger epithelial–stromal attachment. Therefore, we hypothesize that TgV1 EVs have selectively-enriched molecular cargo, targeted to CECs, that facilitates CEH and repair. We further hypothesize that TgV1 EVs are compromised in DM, and multi-omics analyses will specifically identify functional pathways altered by hyperglycemia-associated DM. In Aim 1 we will characterize TgV1 EVs from both healthy and DM mice and study their functional effect on both CECs (in vitro) and the epithelium (in vivo). Our in vitro studies will assess cellular proliferation, differentiation, adhesion, and barrier function. Our in vivo studies will examine the effect on corneal epithelial wound healing (nonpathologic) and non-wounded corneas (by blocking EV uptake), followed by histological and anatomical assessments. In Aim 2 we will conduct molecular studies (transcriptomic and proteomic) on TgV1 EVs (healthy and DM) and CECs (healthy and hyperglycemic, before and after introduction of TgV1 EVs) to identify regulatory mediators that promote or degrade epithelial homeostasis and repair. This research will advance our understanding of the crucial role of CTS EVs and pave the way for the development of novel therapeutics targeting EV-mediated mechanisms in corneal and other ocular diseases.

NIDCR - National Institute of Dental and Craniofacial Research

PROJECT SUMMARY/ABSTRACT Deep tooth injuries and inflammation affect millions of Americans, often progressing into pulp necrosis and treated by removing, i.e. devitalizing, and replacing the dental pulp tissue with artificial materials. Vital pulp therapies (VPTs) have the potential to promote cell signaling that stops the infection and restores pulp health, but their effectiveness is limited once pulpitis is established. This is largely due to the large gap in knowledge of what signaling cascades regulate the immune response to defend the pulp versus promote tertiary dentino- genesis to repair the damage. Studies have demonstrated that sensory axons sprout during infection and injury and communicate with immune and stem cell populations during tissue healing. Insights into how neurons pro- tect and enable dentin repair can therefore create therapeutic strategies that harness this axis to heal, rather than remove, the dental pulp tissue. The long-term goal of this project is to understand the cellular mecha- nisms that protect teeth via immune and mineralizing cell responses to inflammation and damage. The applica- tion objective is to determine the role of calcitonin gene-related peptide (CGRP) in activating immune and min- eralizing cells during tooth healing, i.e. reparative dentinogenesis. Our central hypothesis is that neuronal-de- rived CGRP regulates the function of neutrophils & monocytes, surviving odontoblasts and odontoblast progen- itors via its receptor, receptor activity modifying protein 1 (Ramp1), during reparative dentinogenesis. The ra- tionale for this project is that a detailed scientific framework of cellular crosstalk during reparative dentinogene- sis is likely to identify cell-specific mechanisms that sustain and enhance tooth health. The central hypothesis will be tested with the following specific aims: 1) Determine the cell-specific effects of CGRP signaling after deep dentin trauma; 2) Identify the role of CGRP signaling in regulating inflammation and subsequent tertiary dentinogenesis after direct pulp capping procedures; and 3) Evaluate the effect of increased RAMP1 expres- sion and/or exogenous CGRP on promoting pulp healing and homogeneous mineralized tissue barrier for- mation after direct pulp capping. In aim 1, direct pulp capping will be performed on mice with conditional dele- tions of the CGRP receptor, RAMP1, in immune or mineralizing cells. The dentin pulp complex will be analyzed throughout the healing period of 1-56 days for inflammatory and mineralization responses. For aim 2, a model of pulpal inflammation will be created with an initial shallow injury on molars with lipopolysaccharide applied. This will be drilled out and restored 24 hours later, followed by a similar timeline of investigations into pulpal responses. The last aim proposes to enhance RAMP1 and therefore the ability to respond to CGRP released during injury and inflammation to establish whether this can promote pulp healing and tissue barrier formation. The research proposed in this application is innovative because it provides a clinically relevant model of deep dentin damage and repair with which to study cell-specific repair mechanisms. The proposal is significant be- cause it is expected to identify cellular mechanisms that sustain tooth vitality to advance the development of next-generation VPTs.

NINDS - National Institute of Neurological Disorders and Stroke

PROJECT SUMMARY The Neuroscience, Developmental, and Regenerative Biology Prefreshman Research Experience (NPRE) Program at the University of Texas at San Antonio (UTSA) is designed to increase the retention and success of first-year STEM students through early research engagement, structured mentorship, and academic support. First-year STEM majors are at the highest risk of leaving STEM fields, before they have the opportunity to participate in undergraduate research. The NPRE Program addresses this by offering an 8-week research experience during the summer prior to students’ freshman year, followed by continued mentorship, professional development workshops, and academic resources throughout their freshman year. The NPRE Program is a two-phase initiative that supports students at critical transition points in their undergraduate careers. Phase I provides hands-on laboratory experience, graduate and faculty mentorship, a seminar series, and scientific communication training, allowing students to develop critical thinking and research skills before entering college. Phase II ensures continued support by offering monthly development workshops, structured study hall sessions, mentorship check-ins, and paid research opportunities for students who remain in their Phase I labs, sustaining engagement and persistence in STEM. The University of Texas at San Antonio and NDRB Department are committed to broadening participation in STEM. Data from our pilot programs demonstrate the effectiveness of early research engagement, with two-thirds of NPRE students continuing research beyond their first summer and 93% persisting in STEM degrees. By integrating research, mentorship, and structured academic support at the earliest stages of undergraduate education, the NPRE Program provides a scalable model for improving STEM retention and developing the next generation of scientists.

NIEHS - National Institute of Environmental Health Sciences

Proposal Abstract Traditionally, live animals have been used to assess the toxicity of candidate chemicals in pharmaceutical drug development. However, animal tests are increasingly scrutinized for being time- consuming, costly, and ethically challenging. This has driven demand for non-animal alternative tests, or new approach methodologies (NAMs). The recent FDA Modernization Act 2.0 supports this shift by permitting the adoption of validated NAMs in place of animal tests for safety assessments and regulatory approval of human trials. NAMs can serve as first-tier screening tools to identify potentially toxic drugs, allowing only those with no apparent toxicity to proceed to animal testing if necessary. This tiered approach could significantly reduce live animal use. To achieve this goal, rigorous validation of individual NAMs according to international standards is essential to ensure regulatory acceptance. The proposed project aims to establish validated NAMs for developmental and reproductive toxicity (DART) assessment using morphogenesis models derived from pluripotent stem cells. My lab has previously developed these morphogenesis models from mouse and human stem cells, which recapitulate key morphological and molecular events of early embryogenesis in vitro. In published studies, we showed that these models exhibit significant morphological and gene expression changes in response to chemicals known to cause birth defects or miscarriages. To validate these models as NAMs for DART assessment, we will apply the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline, which provides a list of reference drugs with comprehensive in vivo toxicokinetics data, such as rodent plasma concentrations linked to embryotoxicity and non-embryotoxicity. These data can serve as benchmarks to evaluate the effectiveness of NAMs in predicting embryotoxic drug concentrations in alignment with in vivo results. To accomplish our objective, we propose three Specific Aims. Aim 1 is to examine the impact of embryotoxic drug exposures on the gene expression profiles in the mouse morphogenesis model. Aim 2 is to enhance detection capabilities through molecular augmentation of the mouse morphogenesis model. Aim 3 is to examine the response of a human stem cell-based morphogenesis model in reference to available rodent toxicokinetics data. This project is significant in its potential to establish validated NAMs as non-animal alternatives for preclinical DART assessments. It is innovative in its use of advanced stem cell technology to model embryological processes, facilitating precise concentration-specific analyses aligned with high international standards.

NIA - National Institute on Aging

Peripheral artery disease (PAD) is a progressive condition marked by the narrowing and blockage of arteries supplying the legs, often leading to debilitating leg pain and significant walking impairment known as claudication. While standard therapies exist, their effectiveness is limited, and there remains a critical need for treatments that enhance limb perfusion and function while reducing reliance on costly interventions. Recent clinical trials have suggested that stem cell therapy may hold promise for PAD treatment, yet results have been mixed, with ongoing barriers regarding the optimal cell type, delivery method, and therapeutic targeting. In this proposal, we overcome these barriers by using an autologous cellular preparation (adipose stromal vascular fraction, or SVF), and by targeting the inflow collateral vessels and employing a novel access and delivery strategy to enhance perfusion. We have developed and validated a minimally-invasive porcine model of hindlimb ischemia (percutaneous catheter-based coil occlusion of the iliofemoral and popliteal arteries) which recapitulates key aspects of human PAD and can be a platform for PAD therapy development. We have demonstrated that transvenous periarterial administration (around the porcine aortic trifurcation) of SVF increases long-term arterial inflow to the ischemic hindlimb and improves treadmill performance with respect to sham-treated ischemic hindlimbs. The objective of our proposal is to compare regenerative, cell-based regimens for PAD treatment (including SVF and SVF-derived exosomes) in a clinically relevant animal model of hindlimb ischemia whose size, anatomy, physiology, and comorbidities closely mirror those of human PAD patients. Our central hypothesis is that: (i) delivery of SVF into the peri-arterial region of the aortic trifurcation, in our porcine hindlimb ischemia model, will increase arteriogenesis and improve hemodynamic and functional endpoints more effectively than either intra-arterial SVF delivery or sham treatment; and (ii) SVF vs. SVF-derived exosomes, delivered peri-arterially in the same model, will provide equivalent benefits on the same endpoints. We will test this central hypothesis in three Specific Aims: Aim 1 will compare the effect of transvenous/peri-arterial (aortic trifurcation region) SVF delivery vs. intra- arterial SVF delivery on arteriogenesis, hindlimb perfusion, treadmill performance, and histological endpoints in our porcine model of hindlimb ischemia; Aim 2 will compare the effect of transvenous/peri-arterial (aortic trifurcation region) delivery of SVF vs. exosomes derived from SVF on arteriogenesis, hindlimb perfusion, treadmill performance, and histological endpoints; and Aim 3 will investigate the mechanisms by which SVF or exosomes delivered to the retroperitoneum around the aortic trifurcation drive arteriogenesis. Successful performance of this research proposal should lead to development of arterial inflow-enhancing therapies which would be useful in PAD patients, particularly ones who are not fit, not appropriate, or not willing to undergo a major revascularization procedure.

NHLBI - National Heart Lung and Blood Institute

Summary: Hematopoietic stem cells (HSCs) are vital for sustaining blood lineages and homeostasis in adulthood. While HSC transplantation is a highly effective treatment for bone marrow disorders and blood cancers, its availability is often limited by the shortage of HLA-matched donors. To address this limitation, extensive efforts have been dedicated to developing differentiation strategies for the de novo generation of engraftable HSCs from human pluripotent stem cells (hPSCs), including induced pluripotent stem cells (iPSCs). However, hematopoietic cells derived from hPSC often show limited engraftment capability and sometimes skewed lineage potential, suggesting that essential cues for full functional HSC specification are missing during critical developmental windows. During hematopoietic development, definitive HSCs and HSC-independent progenitors arise primarily in the aortic-gonad-mesonephros (AGM) region. These hematopoietic stem/progenitor cells (HSPCs) originate from hemogenic endothelial cells (HEs) through a process of endothelial-to-hematopoietic transition (EHT), within arterial endothelial cell (aEC) enriched environment. While the requirement of the arterial program in AGM-like HSPC development is recognized, the cellular niche signals guiding cell fate acquisition and HSPC generation remain elusive, especially in humans. This project aims to investigate the role of arterial vascular niche in regulating AGM-like HSPC emergence utilizing autologous endothelial cells derived from iPSCs. We hypothesize that autologous hPSC-derived aECs provide critical niche cues to direct HE fate, promote EHT, and enhance engraftable HSPC generation. We developed a chemically defined, feeder-free monolayer system that recapitulates two distinct waves of primitive and definitive hematopoiesis. In Aim 1, we will characterize the niche effect of autologous aECs on definitive hematopoiesis by investigating whether the niche function requires cell-cell contact, elucidate the molecular mechanism underlying aEC niche function by single-cell RNA sequencing, and develop a new WAS-RUNX1-GFP reporter system to track HE fate, EHT, and HSPC emergence in real time. In Aim 2, we will determine whether aEC- primed HSPCs contain long-term engraftable HSCs by transplantation in immunodeficient mice, and evaluate their self-renewal and multilineage reconstitution capacities. In Aim 3, we will investigate the role of ephrin B2 (EFNB2), a specific gene for arterial specification and Notch signaling target, in aEC niche function by siRNA knockdown, overexpression, and inhibition with specific peptides. Our study will provide mechanistic insights into how the aEC niche regulates human AGM-like HSPC development from iPSCs and offer an in vitro model for the broader understanding of arterial niche signaling in human hematopoiesis.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Project Summary Distinct stomach epithelial cell types, all arising from a common multipotential progenitor (stem cell), serve essential digestive or barrier functions. Defects in the fractions or properties of these cells are associated with various prevalent human disorders, including pre-neoplastic conditions. Pit (surface mucous), isthmus (epithelial self-renewal), neck (deep mucous), and chief (zymogenic) cells –each with distinctive morphology, functions and gene products– are precisely zonated along the long axis of gastric corpus glands. Informed by other self-renewing tissues –such as blood and intestine– and by growing appreciation of epithelial plasticity, each zonated cell type is regarded as a “committed” terminal product of a unidirectional cellular hierarchy that originates in proliferative isthmus cells and retains some capacity to “dedifferentiate”. However, we detect modest transcriptional or epigenetic distinction among the zonated cells and their phenotypes inter-convert readily in vitro and in vivo in response to specific cues: BMP signaling for pit cells and canonical Wnt signaling for neck/chief cells. Our preliminary data therefore suggest the radically different view that pit, neck, and chief cell properties are not hard-wired in the conventional sense of cell “determination”, but represent reversible, signal-responsive phenotypes within a continuum of native cell states directed by finely graded signals from specific sub-epithelial cells. Of mechanistic note, PDGFRA+ sub-epithelial mesenchymal cells positioned near pits are enriched for BMP expression, while Wnt/Rspo mRNAs localize in similar cells positioned near chief cells at the gland base; niche-derived NRG1 concentrates near the isthmus zone. We propose that isthmus cell replication and overt phenotypes of surface and deep corpus gland cells reflect the summation of these sub-epithelial signals. Challenging classical views of a gastric cell hierarchy, this project examines epithelial cell properties with respect to specific niche signals. Mechanistically, two Specific Aims address each side of this paracrine dialogue to decipher the epigenetic basis (Aim 1) and regulatory logic (Aim 2) of the mouse gastric corpus. In Aim 1, five discrete sub-Aims will collectively delineate determinants of zonated corpus epithelial cell properties. We will define how extracellular signals modulate groups of phenotype-restricted cis- regulatory enhancers to generate distinct phenotypes and test whether pit-biased (KLF4) and neck-biased (CREB3L4) transcription factors are required for these effects. Three sub-Aims in Aim 2 will define how key signaling components in the mesenchymal niche act individually and in combination to effect precise zonation. We will determine how individual BMPs, Wnt/Rspo signaling, and NRG1 together influence epithelial zonation and restrict cell replication to the isthmus. Significant gaps in knowledge currently limit actionable insights into gastric mucosal homeostasis, metaplasias, cancer, and other disorders. This project aims to narrow that gap via mechanistic investigation of a dynamic epithelium that continuously renews itself while generating specialized cellular phenotypes in response to an exquisitely graded mesenchymal niche.

National Institutes of Health

The NIH Research Education Program (R25) supports research education activities in the mission areas of the NIH. The overarching goal of this NIH Science Education Partnership Award (SEPA) program is to support educational activities that increase understanding of biomedical research among pre-college (pre-kindergarten to grade12) individuals, and to encourage awareness of and continued interest in careers in science, technology, engineering, and mathematics (STEM).

National Institutes of Health

The NIH Research Education Program (R25) supports research education activities in the mission areas of the NIH. The overarching goal of this NIH Science Education Partnership Award (SEPA) program is to support educational activities that increase understanding of biomedical research among pre-college (pre-kindergarten to grade12) individuals, and to encourage awareness of and continued interest in careers in science, technology, engineering, and mathematics (STEM).

NiSource Foundation

Supports STEM education, workforce development, and community safety programs in NIPSCO and Columbia Gas service areas.