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U.S. Mission to Italy

The U.S. Mission to the Republic of Italy s Public Affairs Section (PAS) is pleased to announce that funding is available through its Public Diplomacy Grants Program. This is an Annual Program Statement outlining funding priorities, strategic themes, and the procedures for submitting requests for funding. PA Italy invites proposals for programs that strengthen cultural ties between the United States and Italy through cultural and exchange programming that highlight shared values and promote bilateral cooperation. All programs must include a significant American cultural element, connection with American expert(s), organization(s), OR institution(s) in a specific field that will promote increased understanding of U.S. policy and perspectives. Priority Program Areas: American and Italian voices countering malign influencers and misinformation campaigns Promoting strong transatlantic relations; Creativity and innovation in education and the arts, and problem solving of issues of mutual interest to both countries; American Studies, particularly American History and Literature, to include university linkages; Promoting diversity and inclusion; Empowerment and prosperity through STEM education and entrepreneurship; American English Language Study; Media Literacy.

U.S. Mission to Chile

Funding Opportunity Description The Public Affairs Section of the Embassy of the United States (U.S. Embassy) in Chile is pleased to announce the availability of funding for public diplomacy programs with Chile. This initiative was developed to support projects proposed by U.S. and Chilean cultural, educational, and other non-profit organizations and/or individuals that fulfill U.S. Embassy goals and objectives: to promote greater understanding of the United States and to foster academic, cultural, and other people-to-people exchanges between the United States and Chile. The Public Affairs Section is particularly interested in projects that support increasing academic and cultural exchanges between the United States and Chile, increasing social inclusion, fostering entrepreneurship and innovation, expanding English language proficiency, cooperating in science and technology, and advancing excellence in journalism. We are looking for proposals with outstanding cultural, educational, and exchange merit that involve geographically, demographically, and socio-economically diverse audiences in Chile. In deciding which projects to support, the Public Affairs Section will give consideration to the full range and diversity of U.S. and Chilean non-profit organizations. Government agencies and for-profit institutions, such as those registered as commercial and/or private businesses are not eligible to receive funding. Preference will be given to U.S. and Chilean individuals and institutions with a proven track record of executing superior cultural and educational events and programs. Preference will be given to proposals that demonstrate the long-term sustainability of the project and in-kind and/or in-cash financial commitments from other funding sources. Priority areas for project funding are: Expanding English language proficiency (priority: reaching public schools, higher education students, and young professionals with an emphasis on improving conversational English and STEM fields); Increased social inclusion (priority: equal rights and opportunities for immigrants, LGBTI individuals, people with disabilities, indigenous communities, and racial minorities, as well as civic education); Fostering entrepreneurship and innovation (priority: projects that multiply the number of women and minority small business owners, including social impact investment and philanthropy); U.S.- Chile cooperation in science and technology (priority: renewable energy, women in STEM and regional initiatives); Increasing cultural exchanges between the United States and Chile (priority: reaching underserved audiences outside of Santiago); Increasing academic exchanges between the United States and Chile (priority: higher education students and the 100,000 Strong in the Americas initiative); Advancing excellence in journalism (priority: investigative journalism). Typical activities include: Speaking tours/public talks by U.S. experts or roundtable discussions by U.S. experts with counterparts in Chile; Activities that foster long-term student and academic collaboration between U.S. and Chilean universities, technical schools and community colleges; Joint U.S.-Chile conferences or meetings that produce concrete advances or other results; Projects that showcase a U.S. model or curriculum; Projects that include innovative uses of social media or virtual interaction to expand and amplify the impact; English language focused activities such as conversation clubs, coding camps, academic writing programs and English for specific purposes. Creative projects that advance one or more of the priority areas. Activities that are not typically funded include, but are not limited to: Social welfare projects, acts of charity, or international development projects; Investments that primarily benefit only one or a few businesses or individuals; Scholarships for the study of English outside of specific Department of State programs; Scientific research that does not include exchange of U.S. and Chilean researchers or students; Projects that are inherently political in nature or that contain the appearance of partisanship/support to individual or single party electoral campaigns; Exchange programs with countries other than the U.S. and Chile; Programs or exchanges focused on children under 16 years of age; Political party activities; and, Projects that support specific religious activities.

U.S. Mission to Tajikistan

Purpose of Public Diplomacy Grants: PDS Embassy Dushanbe invites proposals for programs that strengthen ties between the United States and Tajikistan in priority program areas (see below) in order to highlight shared values and promote bilateral cooperation. All proposed programs must include an American element, either through a connection with American expert/s, organization/s, or institutions/s, usage of American educational/informational resources, or any other activities that promote or contribute to increased mutual understanding between the people of the United States and people of Tajikistan. Competitive proposals will promote continued and sustainable cooperation between the people of the United States and Tajikistan even after the project concludes. Competitive proposals will include partnership with Tajik governmental bodies, and to organizations that have a demonstrated track record of implementing such programs. Examples of programs could include, but are not limited to: Academic or professional exchanges, lectures, seminars, trainings, speaker programs, or workshops; and Artistic, cultural, or sports workshops, masterclasses, joint performances, and/or exhibitions. PDS welcomes proposals that support one of the following priority program areas: TOPIC 1: Counter Gender-based Violence (GBV) Domestic violence (DV) and gender-based violence (GBV) remains a serious issue in Tajikistan and much of the world. In a USAID-funded survey in Tajikistan, 97% of men and 60% of women believed spousal abuse was justified. Cases of GBV and DV are underreported because victims wish to avoid humiliation, reprisal, or social stigmatization, or believe it may have been warranted. Further, authorities wishing to promote traditional gender roles frequently dismiss domestic violence as a family matter or only gave a warning or fine. Government resources for survivors are also limited. Project Audience(s) may include: Religiously or socially conservative communities, especially Tajik men (18-50 years old) High school students (14-18 years old.) Youth and emerging leaders (18-35 years old.) University teachers and students. Labor migrants and spouses of labor migrants. Tajik advocacy groups. Government bodies. Independent media including bloggers and vloggers Countering Gender-Based Violence Project Goal: Empower civil society and communities in Tajikistan to prevent and prosecute cases of Domestic Violence (DV) or Gender-Based Violence (GBV) through community-led initiatives. Project Objectives (may address one or more of the following): Messaging campaigns or awareness raising activities, such as sports diplomacy, should engage and target both men and women. Having men as the face of campaigns, or having men speak to men standing against GBV, demonstrates solidarity and emphasizes that eradicating gender-based violence is the collective responsibility of everyone, regardless of gender. Improve collaboration between civil society, independent media, and the government to identify and address gaps in existing laws and policies that criminalize GBV/DV, provide protections for victims, and establish legal frameworks for persecution. Raise awareness among vulnerable populations about laws, rights, and support services concerning early marriage, domestic abuse, harassment, divorce, alimony, and other civil rights. TOPIC 2: Promoting Women s Economic Empowerment and Entrepreneurship Due to the high rate of male labor migration and unemployment, more Tajik women are exploring ways to financially support their households and communities. However, women entrepreneurs' activities are highly dependent on the effectiveness of the business environment in the country. Moreover, the mountainous regions throughout the country challenge the development of entrepreneurship, as does lack of information, limited access to financing for starting a business, and other socio-economic conditions. Nevertheless, successful small business development creates new employment opportunities in Tajikistan and helps women support themselves and their families. Small businesses are fast becoming the main source of income for women in Tajikistan. Proposed projects should enhance women s participation, promotion, and longevity in the Tajik economy and ability to assume leadership positions. Projects should clearly support the protection of economic rights for women and increase respect for women s rights in society to improve their independence and proactive role in Tajik society. Project Audience(s) may include: Women from rural areas (including the spouses of labor migrants) and women entrepreneurs. Small businesses in rural areas. Business associations. Financial and government institutions. Tourism agencies (including guesthouse and small hotels). Community leaders and youth demonstrating leadership potential in these areas. Women s Economic Empowerment Project Goal: Increase the capacity of women from underserved, rural communities, including the spouses of labor migrants, to participate or increase their participation in the Tajik economy. Improve women's economic opportunities in Tajikistan by increasing the capacity of women to start, establish, or expand their own companies. Project Objectives (may address one or more of the following): Develop the business and technical skills of women in rural communities to increase employability, launch and/or improve their own businesses. Establish and conduct activities with a professional network for women from under-represented communities, including the spouses of labor migrants, to support mentorship relationships and collaborative initiatives among network members that go beyond the conclusion of project activities. o Projects could connect women s entrepreneurship in the development of tourism around newly recognized UNESCO heritage sites. o Increase awareness of tourism initiatives and employment opportunities centered around newly designated UNESCO heritage sites. o Projects could seek to increase participation of women from underserved and target communities in the fields of Science, Technology, Engineering, and Mathematics (STEM). Increase women s knowledge and understanding about their legal rights in society and how to advocate for the respect of those rights. o Increase women s knowledge and understanding about their legal rights in the workplace, including rights related to employment, equal pay, job security, and access to economic opportunities. o Equip Tajik women with the ability to advocate for the recognition and enforcement of these rights. Promote women s economic empowerment and entrepreneurship through support from start-up hubs, corporate social responsibility, and/or access to finance. Emphasis should be placed on strengthening chambers of commerce, entrepreneurs, and core private sector industries through interactions or linkages with U.S. counterparts. o Facilitate access to funding resources and financing opportunities for women entrepreneurs to launch and grow their businesses. o Strengthen organizational capacities of chambers of commerce to support business development of aspiring female entrepreneurs. o Facilitate interactions and linkages between women entrepreneurs, chambers of commerce, startup hubs, and private sector industries in Tajikistan and their U.S. counterparts. TOPIC 3: Sharing America with Tajikistan The United States values innovation, creativity, critical thinking, freedom of expression, democratic principles, economic growth, and security. The United States supports a sovereign and independent Tajikistan, which includes support for a well-informed, discerning public who can inoculate itself against disinformation. Both the United States and Tajikistan have rich cultural traditions as shown in literature and storytelling, theater and performing arts, film, music, dance, sport, and education. Educational, cultural, and other exchange activities are a great way to engage the public, especially at-risk youth and those with neutral views or misconceptions about the United States, in order to bridge our cultures, deepen understanding, and discuss topics of mutual importance. Proposed projects should strengthen understanding between the United States and Tajikistan and advance areas of mutual interest by leveraging the experiences and lessons learned from the United States, while respecting cultural differences. Project Audience(s) may include: Tajik audiences who have not had exposure to the United States before. Youth 16-35. Academia, professors, and teachers. Civil society, non-government organizations, and associations/organizations promoting shared values or areas of mutual interest. Information professionals (media outlets, managers, editors, journalists, influencers). Religious and community leaders. Entrepreneurs and business community advocacy organizations. National and subnational government officials. Project Goal: To share American values, such as freedom of expression, respect for human rights, and celebrate/promote respect for diversity and social inclusion, while also improving access to objective information and increase media literacy and critical thinking skills to analyze mis and disinformation aimed at the United States. Project Objectives (may address one or more of the following): Raise awareness about shared U.S.-Tajik values and partnerships through trainings, workshops, masterclasses, joint performances, or other projects by U.S. and/or Tajik experts. Increase access to American content by Tajik audiences (such as book translations) that promote U.S. democratic and rights-based values. Increase collaboration between local, state, and civil society actors/stakeholders on well-defined social issues affecting both the United States and Tajikistan by sharing U.S. models of government-community engagement, or by working with U.S. experts/peers. Increase the effectiveness of individuals, organizations, and coalitions working to advance and/or advocate for respect and the promotion of human rights. Strengthen the ability of Tajik media professionals to develop accurate and fact-based informational media campaigns through digital skills building and training initiatives based on U.S.-best practices. Increase production and publication of objective, fact-based and editorially diverse media content by Tajik media professionals. Increase critical thinking skills, especially for youth and publics with a neutral or view or misconceptions about the United States, to identify and critically analyze sources of misinformation and disinformation. In addition to the specific requirements listed above by program area, all proposals must: 1. Clearly indicate the primary activity area to which it is being submitted for consideration. 2. Focus on the key public diplomacy audiences and activities specified in the areas, provide programs for underserved geographic regions of Tajikistan, as well as non-elite schools (if applicable); 3. Clearly delineate how elements of their program will have a multiplier effect and be sustainable beyond the life of the grant; 4. Provide a traditional and/or social media plan for marketing program activities and outcome, if applicable 5. Identify the cities/districts in which activities will take place. 6. Identify specific outcomes to be achieved by the end of the grant period. 7. Identify any tools (surveys, beneficiary interviews, focus groups, etc.) that will be developed for Monitoring and Evaluation purposes. Applicants must also demonstrate competency to manage all financial aspects of the project, including participant costs and transparent arrangements of sub-grant relationships with partner organizations, if applicable.

U.S. National Science Foundation

The National Science Foundation (NSF) invites investigators at U.S. organizations to submit proposals for Doctoral Dissertation Research Improvement Grants (DDRIGs) to the Arctic Sciences Section, Office of Polar Programs (OPP) to conduct dissertation-level research about and related to the Arctic region. The Programs that are currently accepting DDRIG proposals are the Arctic Social Sciences (ASSP), Arctic System Science (ARCSS), and Arctic Observing Network (AON) Programs. The goal of this solicitation is to attract research proposals that advance a fundamental, process, and systems-level understanding of the Arctic's rapidly changing natural environment and social and cultural systems, and, where appropriate, to improve our capacity to project future change. The Arctic Sciences Section supports research focused on the Arctic region and its connectivity with lower latitudes. The scientific scope is aligned with, but not limited to, research challenges outlined in the Interagency Arctic Research Policy Committee s five-year Arctic research plan (https://www.nsf.gov/geo/opp/arctic/iarpc/start.jsp). Given that this solicitation is designed to support early career scientists, this Program will also advance research capacity in Arctic sciences, promote workforce development in Science, Technology, Engineering, and Math (STEM). The Arctic Sciences Section coordinates with programs across NSF and with other federal and international partners to co-review and co-fund Arctic proposals as appropriate. The Arctic Sciences Section also maintains Arctic logistical infrastructure and field support capabilities that are available to enable research.

Arizona SciTech / Arizona Department of Education

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

U.S. National Science Foundation

Government and the nation face a talent shortfall in artificial intelligence (AI) and cybersecurity. The CyberAICorps Scholarship for Service (CyberAI SFS) program welcomes proposals that address AI and cybersecurity education and workforce development. CyberAI refers to using AI in cybersecurity as well as providing security and resilience for AI systems. The Scholarship Track provides funding to establish, or to continue, scholarship for service programs with integrated AI and cybersecurity components (CyberAI). Scholarship recipients must be U.S. citizens or lawful permanent residents and work after graduation in the AI or cybersecurity mission of a government organization for a period of at least the length of the scholarship. The Innovation Track supports projects that enhance preparation of AI and/or cybersecurity professionals. Projects may expand existing educational opportunities, curricula, degree programs, educational pathways, methods and interventions, and partnerships among institutions of higher education, government, and employers. Two statutes authorize this program: 15 USC 7442 (cybersecurity) and 42 USC 18993 (AI). CyberAI SFS aligns with the Executive Order 14277 to prioritize AI within scholarship for service programs. CyberAI is managed by NSF s Directorate for STEM Education in collaboration with the U.S. Office of Personnel Management (OPM) and U.S. Department of Homeland Security (DHS).

Fort Worth Symphony Orchestra

To support a series of summer community concerts, to be presented in multiple venues and in connection with STEM-based partnership programs.

ASME Foundation

Supports mechanical engineering education, STEM programs, and innovation through grants and fellowships.

NIA - National Institute on Aging

ABSTRACT The ASPIRE: Alzheimer’s Summer Program Inspiring Research Engagement (T35 mechanism) at the Krieger Klein Alzheimer’s Research Center at Rutgers is designed to inspire and prepare medical students to pursue careers in bridging ADRD research and clinical care. This summer program offers 10-week, full-time immersive research experiences to 10 medical students per summer, under the mentorship of 10 accomplished scientists. These mentors, with active NIH funding portfolios and proven mentoring success, ensure trainees receive high-quality guidance and sufficient resources. The program will establish internal and external advisory committees to ensure optimal learning goals for the students in ADRD research. Participants will engage in research projects spanning epidemiological observational studies, lifestyle and medication clinical trials, data analyses of "big data" (including “omics” and medical chart data), digital health innovations, and basic science (animal, cellular/molecular, neural stem cell and human postmortem tissue systems studies). This hands-on experience will be complemented by exposure to data science and biostatistics through dedicated meetings with a program biostatistician, equipping students with basic yet practical analytical skills essential for addressing complex challenges in ADRD research. The program emphasizes the responsible conduct of research, including practices that enhance rigor and transparency in human subjects and animals research. Students will also participate in the ADRD Translational Work in Progress series, engaging in open discussions and critiques of scientific materials such as grant aims and hypothesis development. This interactive environment motivates critical thinking, collaboration, and scientific communication skills. Internal and External Advisory Committees, each including world-class researchers in neurodegeneration and ADRD, will meet annually to monitor program progress and provide recommendations for improvement. This oversight ensures alignment with the highest standards of mentorship while maximizing each student’s research experience. The program culminates in a symposium where trainees present their research findings, further refining their scientific communication skills. By exposing medical students to ADRD research early in their clinician careers, the program addresses the critical need for developing future physician-scientists dedicated to ADRD, a condition that disproportionately affects older adults, the fastest-growing segment of the U.S. population. The program aims to cultivate future leaders who will advance innovative research, ultimately promoting state-of-the-art, compassionate care for ADRD patients and improving health outcomes for the rapidly growing geriatric population.

NCATS - National Center for Advancing Translational Sciences

PROJECT SUMMARY/ABSTRACT Vici syndrome (VS) is a rare pediatric genetic disorder characterized by profound developmental delay, seizures, immunodeficiency, cardiomyopathy, and progressive motor decline, with a median survival of just 42 months, This devastating disorder is caused by pathogenic variants in the EPG5 gene, which encodes a critical regulator in autophagy. Loss of EPG5 function results in the accumulation of toxic intracellular material and progressive cellular dysfunction. VS is a member of a broader class of diseases known as 'Congenital Disorders of Autophagy' (CDAs), in which core components of autophagy are defective. There are essentially no treatment options for children with VS or other CDAs. We hypothesize that agents that induce pharmacological enhancement of autophagy in VS and other CDAs represent a viable therapeutic strategy. In collaboration with VS families, we have developed and characterized critical preclinical models for VS for therapeutic discovery and validation, including patient-derived induced pluripotent stem (iPS) cells and novel genetically engineered mouse models. These Epg5 mutant mice recapitulate a range of neurological phenotypes seen in VS including biochemical deficits in autophagy, progressive motor dysfunction, and a strong molecular and cellular signature indicative of neuroinflammation. In parallel, we have established a novel engineered iPS cell-based platform for high throughput cell-based screens, which has identified rapamycin-related class of compounds (rapalogs) as enhancers of autophagy in the VS cells. This project will evaluate the therapeutic potential of the rapalog everolimus, an FDA-approved drug with over 14 years of safety data, including well-described use in pediatric populations, leveraging the VS mouse models for in vivo preclinical proof-of-principle studies. In Aim 1, we will define the pharmacokinetics (PK) and pharmacodynamics (PD) of everolimus in the VS mouse model, optimizing dosing regimens to sustain autophagy induction in vivo after extended use. In Aim 2, we will assess the ability of everolimus to slow or halt disease progression in vivo using the VS mouse model. Neurological function and inflammatory response in the VS animal model will be monitored during longitudinal treatment with everolimus. Phenotypic monitoring will include whole animal behavioral assays of motor function and molecular and histological biomarkers of neuroinflammation in various CNS tissues. Successful completion of this project will provide critical preclinical data supporting the repurposing of everolimus for clinical proof of concept in VS patients. Our multidisciplinary team, combining expertise in drug discovery, preclinical disease modeling and analysis in mice, clinical treatment of VS patients, and rare disease research, is well-positioned to advance this therapeutic strategy toward clinical translation in partnership with highly engaged VS families.

NEI - National Eye Institute

Project Summary Retinal ganglion cells (RGCs) send visual information from the retina to the brain via the optic nerve. Their degeneration underlies several major eye diseases affecting vision, including glaucoma, hereditary optic neuropathies, and ischemic optic neuropathies. Normally, RGCs do not regenerate; thus, RGC loss in these diseases is not reversible. One potential strategy for replenishing lost RGCs in patients is to reprogram stem cells and/or glial cells to functional RGCs. Knowledge about how RGCs are generated during embryonic development will greatly facilitate such efforts. During development, RGCs originate from naïve proliferating retinal progenitor cells (RPCs). Key transcription factors functioning at the different stages of RGC differentiation have been identified, and the mechanisms by which these transcription factors interact with enhancers to regulate target genes and promote RGC formation are being unraveled. These transcription factors likely interact with other factors to carry out their functions, but this is a much understudied area. The current proposal focuses on the factors that interact with Atoh7 to promote RGC formation. Atoh7 is a bHLH proneural transcription factor that is specifically required for RGC genesis. Atoh7 activates downstream genes by binding to E-box sequences in the target gene enhancers. However, multiple proneural bHLH transcription factors are expressed in the developing retina, and they are all capable of binding to similar if not identical E-boxes, yet only Atoh7 is capable of efficiently promoting RGC genesis. Using both ex vivo and in vivo assays, we have now shown that the differences between Atoh7 and other related bHLH transcription factors such as Neurod1 in promoting RGC formation lie within the bHLH domain. We have further narrowed down the responsible differences between Atoh7 and Neurod1 to six amino acid (a.a) residues. The locations of these six a.a. residues suggest that they likely provide interfaces for interaction with additional protein patterners, indicating a likely mechanism for Atoh7 to promote RGC differentiation. Our current proposal aims to identify these interacting proteins and characterize their functions. We will achieve our aims using proximity biotin labeling with our newly generated knock-in Atoh7 allele that expresses a fusion protein of Atoh7 and the biotin ligase BioID2. Our preliminary results demonstrate that this is a very feasible approach. Our specific Aims are: 1) To identify proteins interacting with Atoh7 in the developing retina and to characterize the specificity of the interactions. 2). To investigate the function of Atoh7 interacting proteins in RGC genesis. The proteins we will identify that are associated with Atoh7 will provide new research directions regarding how RGC specific gene regulation is achieved and how the RGC lineage is established. The findings will be significant not only for understanding the fundamental process of retinal cell differentiation but also for guiding efforts to regenerate RGCs to treat related retinal diseases.

NHLBI - National Heart Lung and Blood Institute

Graft versus host disease (GVHD) is the major complication associated with allogeneic hematopoietic stem cell transplantation (HSCT). A critical element of the pathophysiology of GVHD is the failure to reconstitute the regulatory T cell compartment which has been shown to be important for the mitigation of GVHD severity. Re- establishment of an effective regulatory network to counterbalance the pro inflammatory milieu by enhancing regulatory T cell (Treg) survival and suppressive capability therefore remains a major challenge in the field. In preliminary studies, we have demonstrated that the interleukin 27 (IL-27)/IL-27 receptor (IL-27R) signaling pathway plays a critical role in the regulation of CD4+ Treg survival and suppressive capability, and that blockade of IL-27 or the IL-27R results in significantly reduced GVHD lethality, increased CD4+ Treg reconstitution, stabilization of Foxp3 expression, and an increase in CD4+ Treg mitochondrial fitness. In addition, our studies have uncovered a previously unappreciated role for the lysosomal glycoprotein, gamma interferon lysosomal thiol reductase (GILT), by revealing that the regulation of IL-27/IL-27R signaling in CD4+ Tregs is mediated by downstream expression of this glycoprotein. Based on these studies, the overall goal of this proposal is to delineate mechanistic pathways by which absence of IL-27R signaling in CD4+ Tregs promotes their survival, enhances their suppressive capability, and alters the alloreactive donor T cell repertoire. Our overall hypothesis is that signaling through the IL-27R regulates CD4+ Treg survival and that blockade of this pathway augments Treg reconstitution and enhances metabolic fitness. Studies in Specific Aim 1 will delineate mechanistic pathways by which blockade of IL-27R signaling in CD4+ Tregs enhances their ability to prevent GVHD-induced lethality. To address this question, we will employ genetically modified murine models to examine the functional relevance of the mTor and autophagy pathways in mediating the suppressive effects of CD4+ IL-27R/ Tregs as well as determine the effect of IL-27R signaling blockade on mitochondrial metabolism. Experiments in Specific Aim 2 will define the role of GILT in the regulation of CD4+ Treg survival and functional suppressive capability and determine the extent to which absence of GILT phenocopies what is observed with CD4+ IL-27R/ Tregs. We will also delineate the effect of lysosomal expression of GILT on mitochondrial function and oxidative phosphorylation in CD4+ Tregs. Studies in Specific Aim 3 will characterize how absence of IL-27R signaling in CD4+ Tregs alters the alloreactive and regulatory T cell repertoires during GVHD. To address this question, we will employ newly developed bioinformatic pipelines that utilize both single cell paired alpha/beta T cell receptor RNA sequencing and single cell RNA transcriptomics to provide integrated clonal definition and transcriptional profiles for donor T cells residing in GVHD tissue sites. The overall objective of these studies is to develop new insights into the pathophysiology and regulation of GVHD that will foster the development of clinically relevant strategies to mitigate this complication in allogeneic HSCT recipients.

NEI - National Eye Institute

PROJECT SUMMARY Gene therapy for the treatment of autosomal recessive disorders by supplementation with wild-type (WT) copies of the affected gene has been tested in FDA-approved trials. However, strategies for treating autosomal dominant (ad) disorders, which require the removal of a gain-of-function allele through precise genomic repair, have been tested preclinically but have not been evaluated in human subjects. In this proposal, we aim to overcome long standing obstacles to the treatment of RPE65 D477G dominant disorders using autologous induced pluripotent stem cell (iPSC) transplantation. The central hypothesis is that patient-derived iPSC RPE (iRPE) grafts repaired by CRISPR in vitro are a therapeutic option to treat RPE disorders. We will use allele- specific CRISPR-edited RPE65 D477G iRPE to confirm functional repair and differentiation in Aim 1a, and the genomic integrity will be validated via WGS in Aim 1b. The therapeutic potential of iRPE transplantation will be assessed when transplanted into a retinitis pigmentosa preclinical mouse model, Rpe65rd12;Prdcscid. By comparing phenotypes induced by transplantation of repaired iRPE vs. control RPE lines, we will assess whether in vitro CRISPR-repaired iRPE halts disease development in the context of an ad disorder. Our objective is to identify ways to leverage patient stem cells as a tissue source for regenerative medicine. Aim 2 will determine whether patient iRPE repaired in vitro functionally integrate into the retinal circuitry of live mice and rescue vision. Lastly, Aim 3 will determine whether transplanted iRPE is safe and nontumorigenic through long-term analysis.

Avangrid Foundation

Supports STEM education, sustainability, and community development programs in NYSEG, RG&E, and CMP service areas.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT ABSTRACT Reported penicillin allergies affect over 10% of patients (greater than 34 million patients in the United States), yet over 95% of affected patients can tolerate penicillin. These largely inaccurate labels are termed penicillin allergy labels (PALs). PALs are associated with increased utilization of second-line antibiotics, multidrug- resistant infections, and mortality. Guidelines recommend PAL evaluation as a part of antimicrobial stewardship programs, and the recent development of clinical decision rules facilitates PAL testing in a variety of clinical settings. Removing the label, or “delabeling” through penicillin allergy evaluation immediately improves utilization of first-line antibiotics. Patients who have received hematopoietic stem cell transplants (HCTs) are likely particularly vulnerable to harms associated with PALs, as they are immunocompromised, with a high incidence of infection- and disease-related complications that are affected by antibiotic selection (e.g., multidrug-resistant infections, graft-versus-host disease). Yet, to date, there have been few efforts to understand and address PALs in this high-risk population, despite evidence that PALs are a widespread and modifiable driver of poor outcomes in the general population. To address this gap in actionable knowledge, we will quantify risks associated with having a PAL at the time of HCT, and use implementation science framework to guide a qualitative study to inform an intervention. Aim 1 will utilize data from the Center for International Blood and Marrow Transplant Research (CIBMTR), a National Institutes of Health-supported research organization, to investigate whether having a PAL at the time of HCT increases the risk for bloodstream infections, graft-versus-host disease, and mortality. Aim 2 will examine preferences for, barriers to, and facilitators of PAL evaluation in the transplant center using the integrated- Promoting Action on Research Implementation in Health Services (i-PARIHS) framework. Aim 3 will evaluate the acceptability and feasibility of a pharmacist-led strategy using the clinical decision rule PEN-FAST to guide a penicillin allergy testing approach at Yale New Haven Hospital, which performs 170+ HCTs yearly. The PI, Ami Belmont, MD, is an allergist and immunologist, with relevant experience in health services and drug allergy epidemiology research. Her committed mentorship team brings expertise in clinical epidemiology, data registries, implementation science, qualitative and mixed methods, clinical trials, drug allergy, stem cell transplantation, and infectious disease to support the interdisciplinary training and study aims. The advanced training proposed in this award will support Dr. Belmont to develop expertise in advanced clinical epidemiology, implementation science and mixed methods, and clinical trials. Upon completion of this award, Dr. Belmont will be prepared to successfully transition to an independent Physician-Scientist focused on developing novel, scalable strategies to promote antibiotic allergy testing and optimization of first-line antibiotic utilization to improve patient outcomes among high-risk populations, including patients undergoing HCTs.

NINDS - National Institute of Neurological Disorders and Stroke

Project Summary/Abstract The objective of this R21 application is understand how axon guidance genes contribute to the neuropathogenesis of amyotrophic sclerosis (ALS) and frontotemporal dementia (FTD), two devastating neurodegenerative disorders that lie on either end of a clinical disease spectrum. Among more than 40 different genes implicated in ALS/FTD, X-linked mutations in the ubiquitin (Ub) chaperone UBQLN2 cause diverse neurologic phenotypes, ranging from pure ALS with or without FTD, to primary lateral sclerosis and spastic paraplegia. ALS/FTD-associated mutations in UBQLN2 promote its aggregation; however, the mechanisms whereby UBQLN2 mutations instigate neurodegeneration in ALS/FTD are unclear. Our group employs a “fly to human” approach in which genetic modifier screens in Drosophila yield candidate UBQLN2 toxicity pathways that are then tested for phenotypic modulation in inducible pluripotent stem cells (iPSC)-derived motor neurons (iMNs) containing ALS-associated mutations in UBQLN2. One key to these studies has been the development of a combinatorial UBQLN2 mutant (UBQLN24XALS) harboring four different clinical mutations that further reduce its solubility, providing a sensitized system for the identification of UBQLN2 modifier pathways in flies and iMNs. Unbiased genetic screens identified the Unc-5 and Frazzled (Fra) axon guidance genes as determinants of UBQLN24XALS toxicity in flies. Fra is an attractive netrin receptor that promotes the movement of neuronal axons toward netrin ligands while Unc- 5 binding to netrin promotes axonal repulsion. Unc-5 and Fra also function as neuronal dependence receptors that promote apoptotic cell death in the absence of ligand binding. Suppression of human Unc- 5 orthologs UNC5B and UNC5C, or the Fra ortholog DCC (deleted in colon carcinoma) suppressed toxicity phenotypes in human inducible motor neurons (iMNs) harboring a UBQLN24XALS knockin mutation, suggesting that UNC5 and DCC are conserved mediators of UBQLN2 neurotoxicity. Based on these findings we propose that UNC5 and DCC signaling plays a deleterious role in ALS/FTD-UBQLN2 and further hypothesize that aberrant UNC5-DCC signaling may be a disease driver in both genetic and sporadic forms of ALS/FTD. These ideas will be tested using iMN models and a novel humanized UBQLN24XALS knockin mouse model that recapitulates histopathologic and behavioral features seen in UBQLN2-ALS/FTD patients. The objectives of the proposal are to: (i) Define the mechanism of UBQLN2 toxicity suppression by UNC5 and DCC inhibition; and (ii) Test whether UNC5 signaling contributes to neurodegenerative phenotypes in 4XALS mice. Successful completion of these aims will provide mechanistic insights into ALS/FTD-UBQLN2 and prompt further study of UNC5, DCC, and their netrin ligands as therapeutic targets for the treatment of ALS/FTD.

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary Pseudomonas aeruginosa (Pa) is an opportunistic and increasingly antibiotic resistant Gram-negative bacterium that is one of the major causes of chronic nosocomial infections in the United States. The colonization of Pa within a host is often linked to the bioavailability of nutrients, such as iron, and Pa has multiple iron acquisition pathways that allow it to adapt readily to the variety of environments it may encounter within a human host. Pa responds to these dynamic environments commonly through the use of two-component signal transduction systems (TCSs) that are important mediators of signal transduction and allow pathogens to detect chemical and/or physical changes in the environment in order to control basic cellular processes. Previous studies have identified a biofilm and quorum sensing TCS known as BqsRS (also known as CarRS) that regulates biofilm formation and decay in Pa through the sensing of extracytoplasmic Fe2+ and Ca2+. Among its targets, the BqsRS TCS is known to regulate rhlAB and rhlC, critical genes for rhamnolipid production and biofilm formation that are also known to be connected to iron homeostasis and antibiotic resistance. Moreover, the deletion of either bqsR or bqsS in PAO1 results in a significant increase in biofilm formation but reduced biofilm dispersion, the latter of which is important for downstream infections. These observations highlight the importance of the BqsRS TCS to Pa virulence, but there is a foundational lack of understanding regarding the structure, the selectivity, and the mechanism of this system. The ultimate goal of this proposal is to generate a mechanistic and functional understanding of BqsRS at atomic, molecular, and organismal levels in order to exploit this system as a means of reducing or stemming the virulence of opportunistic pathogens such as Pa. The objectives of this exploratory grant are to determine the structural and molecular characteristics of BqsRS, to define how these properties govern BqsRS metal selectivity and function, and to examine a new role of the BqsRS system in regulating the Feo system in P. aeruginosa. Ultimately, the accomplishment of this exploratory grant will deliver fundamental mechanistic insight into a critical metal-sensing TCS and lay the groundwork for future studies that may be designed to target this system and its homologs for additional bacterial exploits.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY Lung injury can lead to improper repair and regeneration, promoting chronic diseases like emphysema and fibrosis. Following severe injury, basal stem cells migrate into the alveolar niche, displacing local AT2 progenitors and creating a “stem cell collision,” where basal cells outcompete AT2 cells, disrupting normal tissue repair. This impairs the AT2 cells’ ability to restore homeostasis through euplastic regeneration. Our preliminary data suggests that this basal cell invasion generates an injury-induced tissue niche (iTCH) comprised of basal stem cells and Pdgfra+ alveolar fibroblasts (AF1s), which are activated during injury and establish a signaling feedback loop, including Notch and Wnt pathways. In mice, AF1 cells are the primary mesenchymal response to injury, differentiating into AF2 cells. This differentiation is unidirectional, with minimal AF2 proliferation or AF1 reversion. We also found that basal cell invasion is regulated by Trp63 expression and Sox2, which suppress basal cell expansion after injury. Notably, iTCH formation is controlled by Notch signaling in AF1s, not basal stem cells. Loss of Notch signaling in AF1s disrupts iTCH formation and prevents dysplastic repair, a feature observed in human fibrotic diseases, including post-COVID-19 fibrosis. In contrast, chronic diseases such as COPD show altered Wnt signaling. These findings suggest that aberrant signaling in iTCHs could serve as a biomarker for lung diseases. We hypothesize that an emergent niche after acute injury determines whether tissue repair is dysplastic or euplastic by rewiring signaling pathways between lung cell lineages. The study aims to further investigate these pathways to better understand the mechanisms of lung repair.

OD - NIH Office of the Director

Project Summary. We request a BD FACSDiscover S8 Cell Sorter to bring advanced image-based and spectral sorting capabilities to UCLA, enabling high-throughput analysis and isolation of cells based on spatial features, intracellular localization, and cell-cell interactions—capabilities not possible with conventional flow cytometers. Housed in the Broad Stem Cell Research Center and supported by the David Geffen School of Medicine, the instrument will serve NIH-funded investigators across fields including immunology, oncology, developmental biology, and biomedical engineering. The S8’s real- time imaging enables sorting of nanovial compartments based on direct tumor–immune cell contact, spatial RNA localization such as XIST nuclear foci, or the presence of phase-separated RNA droplets in live cells. Its spectral flow cytometry allows flexible, high-parameter panels for identifying rare hematopoietic stem cell subsets, profiling nanoparticle uptake, and assessing complex immune activation signatures without extensive compensation. These features directly support cutting-edge projects such as nanovial-enabled T cell functional screening and sorting based on secreted cytokines, growth or reporter activation. Together, these capabilities will allow researchers to interrogate rare and dynamic cell states with unprecedented precision, advancing efforts to understand and treat cancer, autoimmune diseases, infections, developmental disorders, and enabling next-generation gene and cell therapies.

Best Buy Foundation

Funds teen tech centers and STEM programs preparing youth from underserved communities for tech careers.

NIDCD - National Institute on Deafness and Other Communication Disorders

Human pluripotent stem cells (hPSCs) have been demonstrated to be powerful tools to study human biology and diseases, especially for which human tissue is difficult to access to and biopsy is challenged to obtain. Inner ear is one of organs that is nearly impossible to access without causing damages. Moreover, it is rare to obtain human inner ear biopsy. However, inner ear disorders, including hearing loss and vestibular dysfunction, are one of the most common sensory disorders. Although animal studies have advanced our understanding in hair cells, the underlying cellular processes may differ from those of human. A human cell-based model is therefore needed to progress our understanding of inner ear and the development of therapeutic strategies. Recently, stem cell-derived three-dimensional (3D) inner ear organoids have been reported to mimic certain aspects of inner ear development and disease pathologies in vivo. Despite this potential, there are limitations in the 3D inner ear organoid system to faithfully recapitulate some developmental processes, e.g., morphogen gradients that are critical for proper patterning. Therefore, we first propose to develop an innovative microphysiological system featuring a microfluidic chip that can precisely establish desired morphogen concentration gradients to which large size, 3D organoids are subjected on-chip (Aim 1). We will mediate BMP, WNT, and SHH signaling pathways to model dorso-ventral patterning in otic vesicles as a proof of concept. Results will assist us to understand how to induce the proper dorso-ventral patterning such that a similar strategy can be applied to effectively induce ventralization in the hPSC-based inner ear organoid system. As many inner ear disorders stem from malfunction of or damages in hair cells, we then propose to understand regulatory processes for the hair cell formation with special focus on epigenetic regulatory mechanisms, which is poorly understood, using the hiPSC-derived 3D inner ear organoid system (Aim 2). We propose to generate comprehensive epigenetic and transcriptomic regulatory networks for nature occurring hair cell differentiation and post-damage-induced hair cell regeneration using single cell (sc) muti-‘Omic approaches. Furthermore, we will validate the findings from sc multi-‘Omic approaches by testing the effects of the identified regulatory enhancer regions and genes in hair cell regeneration using CRISPR/dCas9-based assays (Aim 3). This will allow us to mimic epigenetic regulation of gene expression during hair cell formation. This project is not only improving the technology for the organoid system, but also providing the first step towards systematically advancing our knowledge of the role of epigenetics in human hair cell formation and, ultimately, developing therapeutic strategies for damaged hair cells.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY/ABSTRACT Cardiac IKr is a critical repolarizing potassium current shaping the human ventricular action potential. It is conducted by heteromeric assemblies of the human ether-à-go-go-related gene (hERG1) 1a and 1b subunits. These subunits are encoded by alternate transcripts of the hERG/KCNH2 gene and differ only in their amino- terminal regions. hERG1a/1b heteromerization is vital for normal CM function, as the imbalance of subunit expression and/or function results in cellular pro-arrhythmic behaviors. hERG1a/1b assembly is mediated by the co-translational association of the encoding mRNAs in HEK293 cells, cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs), and human myocardium. Evidence suggests that interaction between the nascent proteins is not required for the co-translational complex assembly. This grant's preliminary findings indicate that this complex assembly occurs post-transcriptionally and is promoted by direct interactions between hERG1a and 1b mRNAs governed by their secondary structures. In preliminary studies, RNA binding proteins DDX3X and DDX5 were identified as part of the complex, and purified DDX3X promoted hERG1a/1b mRNAs' association in vitro. In the K99 phase, I will define the mRNA structural features promoting the co-translational association and determine the affinity and energies of the RNA/RNA interaction using in vitro systems, isothermal calorimetry (ITC), mutagenesis, hybrid protein-RNA immunoprecipitation (RIP), and live-cell imaging. I will also determine whether DDX3X and DDX5 affect hERG1a and 1b mRNAs stability, translation, and association in hiPSC-CMs using qPCR, electrophysiology, Western Blot, ribosome profiling, RIP, and single molecule fluorescent in situ hybridization (smFISH). I will use quantitative ITC and in vitro reconstitution approaches to determine the specificity, affinity, and energies of the interaction between purified DDX3X and DDX5 with hERG1a and 1b mRNAs. I will also evaluate if DDX3X and DDX5 promote the association of the mRNAs in in vitro systems. In the R00 phase, I will determine whether the stability, translation, and association of hERG1a and 1b mRNAs are impaired in arrhythmias associated with type 2 long QT syndrome (LQT2). I will use hiPSC-CM disease models to evaluate half-life, translation rate, and association of the mRNAs with qPCR, ribosome profiling, RIP, and smFISH. These experiments will contribute to understanding ion channel biogenesis and elucidate molecular mechanisms underlying LQT2 related arrhythmias. This proposal is designed to fulfill my short-term goals of expanding my skills in cardiovascular research and biophysics and transitioning into the independent phase of my career. This will ultimately allow me to obtain my long-term purpose of linking RNA and ion channel biophysics to translational cardiovascular research.

U.S. National Science Foundation

The Biological Anthropology Program seeks to advance scientific knowledge about the processes that have shaped biological diversity in living and fossil humans and their primate relatives through support of basic research on human and primate evolution, biological variation, and interactions between biology, behavior and culture. The program supports a portfolio of research that demonstrates engagement with biological anthropological and evolutionary theory; includes diverse and interdisciplinary methods in field, laboratory and computational settings; encompasses multiple levels of analysis (e.g., molecular, organismal, population, ecosystem) and time scales from the short-term to evolutionary; and considers the ethical implications and societal impacts of the research. The program also supports a wide range of broader impact activities as part of research grants, including research outcomes with inherent benefit to society, efforts to broaden participation in science, technology, engineering, and mathematics (STEM) training, research and outreach activities and other evidence-based activities developed within the context of the mission, goals and resources of the organizations and people involved. The program contributes to the integration of education and basic research through support of dissertation projects conducted by doctoral students enrolled in U.S. universities. This solicitation specifically addresses the preparation and evaluation of proposals for Doctoral Dissertation Research Improvement Grants (DDRIG). Dissertation research projects in all of the subareas of biological anthropology are eligible for support through these grants. These awards are intended to enhance and improve the conduct of dissertation research by doctoral students who are pursuing research in biological anthropology that enhances basic scientific knowledge.

NHLBI - National Heart Lung and Blood Institute

Project Summary Trabecular bone marrow contains two anatomically distinct yet functionally interdependent niches that support hematopoietic stem cells (HSCs): the endosteal niche, which promotes dormancy and self-renewal of long-term HSCs, and the vascular niche, which supports actively cycling short-term HSCs and ongoing hematopoiesis. These compartments coordinate bone remodeling and hematopoiesis, but the mechanisms underlying their integration remain poorly understood due to the anatomical inaccessibility of the bone cavity and the lack of physiologically relevant preclinical models. This proposal aims to develop a biomaterials-integrated bone–marrow microphysiological system (MPS) that recapitulates the structural and functional interdependence of the bone and marrow compartments and enables dynamic analysis of HSC behavior. The platform integrates two advanced biomaterials: demineralized bone paper (DBP), an osteoid-like matrix that supports osteoblast mineralization and osteoclast-mediated remodeling, and an inverted colloidal crystal (ICC) hydrogel scaffold that mimics the sinusoidal architecture of marrow and supports stromal–hematopoietic interactions. The central hypothesis is that integrating these components within a silicon-based perfusion chip will enable high-fidelity modeling of dynamic bone marrow niche processes with precise experimental control and microscopic access. Aim 1 will establish the bone–marrow MPS by seeding BMSCs and osteoblasts into their respective biomaterials, validating niche-specific stromal phenotypes, and recapitulating bone remodeling. CD34⁺ HSCs will then be introduced to assess how integrated versus separated configurations of the bone and marrow compartments differentially regulate HSC behavior. Aim 2 will validate the bone–marrow MPS by recapitulating autologous HSC transplantation scenarios following preconditioning. Donor-matched bone–marrow MPS units will be established, and HSCs derived from a different donor will be introduced with and without fractionated irradiation. By comparing HSC engraftment outcomes, the MPS’s ability to replicate known features of clinical transplantation will be demonstrated. This human-relevant bone–marrow MPS platform will provide new insights into bone–marrow crosstalk, preconditioning regimens, and HSC processes. It offers a scalable, high-resolution system for studying hematopoiesis, transplantation biology, and therapeutic interventions—aligned with NIH priorities in the NOSI: Bold New Bioengineering Research for Heart, Lung, Blood, and Sleep Disorders.