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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

NDEP STEM Open NFO

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

<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>

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).

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.

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.

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.

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.