Case Western Reserve University

NIH Research Projects · FY 2025 · 2000-08

A central question in neuroscience is how sensory stimuli in the environment are represented. The olfactory system is an attractive sensory modality to approach this question since the major excitatory pathways that connect receptor neurons, second-order mitral cells in the olfactory bulb, and tertiary neurons in olfactory cortex are well understood. However, intracellular recordings demonstrate that neural representations of odors in second-order neurons (mitral and tufted cells) do not result exclusively from feedforward input from receptor cells. Instead, the output of the olfactory bulb results from complex interactions between excitatory and inhibitory circuits. Relatively little is known about the neural circuits that generate inhibition onto principal cells. This proposal uses rodent brain slice recording methods to determine how local circuit pathways excite GABAergic olfactory bulb interneurons that shape the firing patterns in principal cells. Using both whole-cell intracellular recording and live 2-photon imaging methods, we will determine how the key synaptic pathways that enable sensory input to excite granule cells function. The proposed study will test the hypothesis that GABAergic granule cells are excited by two parallel synaptic pathways activated by sensory stimuli. This work also will define the different roles played by this newly discovered circuit and well-established dendrodendritic excitation. The proposed work also will reveal how bulbar local circuits enable glomerular-specific inhibitory coding in mitral and tufted cells. Defining the cellular mechanisms that generate sensory-evoked inhibition in the olfactory bulb, the overall focus of this proposal, is critical to understand how biological information is represented in the brain. The proposed studies also are significant as they represent an important step toward understanding the specific deficits in many major neurodegenerative diseases in which olfactory function is affected. In many of these diseases, sensory impairments occur early in the disease onset. Insights into the specific olfactory mechanisms affected in these diseases may lead to directly testable hypotheses regarding analogous mechanisms in the cortical areas responsible for the cognitive deficits commonly associated with neurodegenerative disorders.

NIH Research Projects · FY 2025 · 1999-07

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. This proposal describes our “Integrated Neural Engineering and Rehabilitation Training” program that produces biomedical engineering Ph.D. graduates who combine state-of-the-art expertise in neural engineering (an area of bioengineering) with a genuine appreciation of the practice and challenges of clinical rehabilitation. This T32 is centered in the Department of Biomedical Engineering at Case Western Reserve University but also includes the strong participation of several of our local medical centers. Our T32 is focused exclusively on predoctoral training - having trained nearly 100 students since 1999, 66 in the last 15 years. We request funding for 9 predoctoral positions per year for five years and have an institutional commitment to supplement tuition, stipend, and training resources. We expect to train up to 27 BME Ph.D. students for two years each over the proposed 5 years. Trainees enter with undergraduate training in engineering or a closely related discipline. They satisfy the rigorous requirements of the BME Ph.D. program and benefit from its existing features, while our T32 program adds value through highly collaborative and interdisciplinary research projects, a clinical immersion experience, and unique access to visiting seminar speakers. Over the next 5 years, we will create and pilot AI-in Education activities and continue oversight with our established external Advisory Committee comprised of academic leaders in rehabilitation and neural engineering, representatives of large and small companies in the stimulation and rehabilitation commercial space, and practicing neural/rehabilitation physicians. The specific objectives of our training program are: (1) Prepare our trainees for productive careers in rehabilitation and neural engineering; (2) Provide a rigorous engineering education that forms the basis for future innovation; (3) Provide specific expertise in the development and application of neural stimulation and interventions for overcoming neurological disorders; (4) Provide specific expertise in modeling and simulation; (5) Provide an extensive, hands-on clinical immersion experience that prepares each trainee for a translational career; (6) Provide specific expertise in the deployment and integration of Brain-Computer Interfaces; and (7) Provide real-world professional development training to enhance post-graduation success. We have assembled a distinguished group of mentors who serve in one of three roles: Research Training mentors who are the primary research advisors of the trainees, Associate Research Training Mentors who are content experts on T32 trainee committees, and Clinical Training Mentors from rehabilitation and surgical disciplines who ensure the clinical relevance of each trainee research project. Trainee project topics include electrode development, stimulation pattern design, neural motor control mechanisms, neural biomaterials, immunomodulation of the neuroinflammatory response, deployment of interventions to individuals with neurological disorders, neurorehabilitation, modeling and simulation, and brain-computer interfacing.

NIH Research Projects · FY 2026 · 1997-08

The mission of the Case Comprehensive Cancer Center (Case CCC), now in its 34th grant year, is to develop high-impact and comprehensive cancer research programs in an environment that fosters scientific discovery, spans prevention, facilitates early detection, stratifies risk, promotes therapies, and finds cures to ultimately improve lives across its communities. The Case CCC’s geographic outreach addresses the individual needs of patients in the catchment area. This approach empowers innovation and discovery in clinical care reflecting an unyielding commitment to impacting cancer care in the catchment area and worldwide. The Center coordinates all aspects of cancer research in Cleveland and Northern Ohio, including activities of the affiliate institutions of Case Western Reserve University, Cleveland Clinic, and University Hospitals. The Case CCC is organized around 6 Research Programs, 10 Shared Resources, and a clinical and behavioral cancer research infrastructure that prioritizes innovative translational research and investigator-initiated clinical trials that cut across the Research Programs. The Center promotes the education and training of the next generation of cancer-focused scientists and healthcare professionals and seeks to promote a research community distinguished by academic and organizational excellence. The Case CCC includes 288 full members from 8 schools and 46 academic departments who actively participate in Center activities which promote a transdisciplinary approach that facilitates discovery and clinical application. The cancer focus of the Center is exceptional, with over $87M in direct funding and over $30M in direct NCI funding. Institutional commitment is also exceptional, codified through an updated Memorandum of Understanding. The consortium members will provide over $220M of internal funds for cancer research in the next grant cycle. The Case CCC and its affiliate institutions have established an outstanding infrastructure that enables its members to improve the prevention, diagnosis, and treatment of cancer through discovery, implementation and dissemination, and collaborative transdisciplinary research while providing state-of-the-art care and treatment to cancer patients and their families. Case CCC members identify new therapeutic targets, make drug discoveries, develop new imaging tools, and pursue innovative clinical trials with novel small molecules and immune therapeutics. The core principles of the Case CCC are reflected in the updated Strategic Plan, including bi-directional engagement to build trust within the community. The Case CCC yields tangible benefits as an active partner with the NCI by supporting cancer relevant scientific research with direct benefit to patients and the general public.

NIH Research Projects · FY 2025 · 1997-04

Modified Project Summary/Abstract Section The RUSTBELT Center for AIDS Research (CFAR) is a close partnership between Case Western Reserve University and the University of Pittsburgh. The MPIs for the RUSTBELT CFAR are Dr. Jonathan Karn at CWRU, who has led the CWRU/University Hospital CFAR since 2008, and Dr. Sharon Hillier at the University of Pittsburgh, a leader in HIV prevention research. By combining the two complementary programs in Cleveland and Pittsburgh, a broader range of services and activities is offered. The research strengths in Cleveland and Pittsburgh will leverage complementary skills to increase the impact of our NIH-funded research through the development of regional interdisciplinary teams. The RUSTBELT CFAR has 242 members (216 Full; 41 Associate; 26 International) and an NIH-funded research base exceeding $45 million. The CFAR aims to: (1) provide scientific and administrative leadership to position it at the forefront of HIV research (Administrative Core A); (2) support new faculty development (Developmental Core B); (3) pursue innovative studies in the US with samples from HIV+ individuals in Uganda (Uganda Core C); (4) support advanced clinical research with access to extensive clinical cohorts, numerous tissue samples, cutting-edge clinical assays, and community outreach (Clinical Sciences Core D); and (5) develop and expand research infrastructure for innovative interdisciplinary HIV research (Viral Pathogenesis & Persistence Core E; Systems Biology and Biostatistics Core F). These highly interactive cores will provide access to advanced technologies, bioinformatics, and expertise, while actively developing new approaches shared between the two institutions. Two scientific strategic working groups, led jointly by mid-career investigators from each institution, will promote new research initiatives focused on HIV Across the Lifespan (HAL) and Ending the HIV Epidemic (EHE). The CFAR will focus more on HIV prevention in Cuyahoga County, one of 48 counties prioritized in the Presidential plan to end the epidemic, building on the success of AIDS-free Pittsburgh in Allegheny County. Strong institutional support from each university, along with active community engagement, provides a solid foundation for successfully implementing the research plan. In summary, through its scientific leadership, mentoring, pilot funding, core facilities, community outreach, and access to unique clinical specimens from Uganda, the RUSTBELT CFAR has positioned its investigators at the forefront of HIV/AIDS research.

NIH Research Projects · FY 2025 · 1997-04

ABSTRACT Overall Component The Visual Sciences Research Center (VSRC) at Case Western Reserve University (CWRU) requests continuing support for a P30 Core Grant for Vision Research. The VSRC was founded in 1996 and has undergone tremendous growth since the first P30 grant award in 1997 and subsequent grant renewals in 2002, 2007, 2011, and 2016. The CWRU P30 Core Grant has enhanced and expanded individual investigators’ programs, facilitated inter-investigator and inter-departmental collaborations, and helped bring new investigators within CWRU to the visual sciences, both junior and established. Our VSRC is now comprised of 36 PIs in 13 clinical and basic science departments from the two CWRU Schools and the CWRU College of Arts and Sciences. These investigators conduct innovative, impactful, and interdisciplinary research on fundamental mechanisms in the retina, causes and treatment of common retinal diseases as well as study normal and pathologic processes in the anterior segment of the eye. Our current NEI grant portfolio is diverse and encompasses many funding mechanisms. These include 14 eligible NEI R01s, 1 NEI UG1, 3 NEI R21s, 1 NEI T32, and 2 NEI F30 grants. In addition, our VSRC investigators hold 20 grants from other NIH Institutes. The VSRC is strongly supported by the CWRU School of Medicine, University Hospitals Cleveland Case Medical Center, and the CWRU Department of Ophthalmology and Visual Sciences, which provide significant funds for bringing new PIs to vision research, repair and purchase equipment, service contracts, a partial salary support of the core managers as well as on the seminar series and annual VSRC symposiums. We request support for the 3 resource Cores: 1) Specialized Animal Resources; 2) Molecular Biology and Genotyping; and 3) Analytical Services. All three Cores are expected to be heavily utilized and lead to successful accomplishment of the three unifying grant’s Specific Aims: 1) to enhance the capabilities and productivity of the eligible NEI R01 holders as well as other VSRC investigators by providing them with services, resources and facilities that are too costly for an individual laboratory; 2) to increase scientific interactions among the VSRC investigators by sharing resources and expertise; 3) to bring new investigators to vision research, both junior and established.

NIH Research Projects · FY 2025 · 1993-06

PROJECT SUMMARY/ABSTRACT Ensuring that the next generation of cancer researchers is developing not only the skills to perform high-caliber basic research, but also a deep appreciation for the disease as clinicians see it, is critical for bridging the divide between bench and bedside. To address this need, we developed the current iteration of our NCI-funded T32, entering its 25 year, named the Cancer Biology Training Grant (CBTG). The CBTG draws on 50 Case Comprehensive Cancer Center (Case CCC) research mentors to train 3 postdocs and 1 predoc. The Case CCC is a matrix Cancer Center based at Case Western Reserve University (CWRU) linking all cancer-related research efforts across three institutions: CWRU, University Hospitals (UH), and the Cleveland Clinic (CC). Distinguishing features of the current CBTG application include: (i) a highly supportive environment, as Case CCC earned an “Exceptional” rating at its most recent CCSG renewal in 2018; (ii) innovative training program comprised of four major pillars: Mentored Research, Career Enhancement activities, a Clinical Perspective, and a robust Curriculum; (iii) Mentors that provide a wealth of opportunities for cancer biology training, interconnected through programmatic activities across the Center; and (iv) a highly selective trainee pool together with productive research careers for those appointed to the program. Many activities for appointees are T32-specific/selective, including robust grant-writing and reviewing experience, mentoring of undergrads in our summer undergraduate research program (CanSUR), an IDP Dinner with the PD and AD, attendance at Junior Faculty Mentoring sessions, experience organizing a retreat, and attendance at the Cancer Biology Training Consortium (CABTRAC) annual meeting. Clinical Perspective elements include a Case CCC Bench-to-Bedside Retreat, monthly Cancer Biology Trainees’ Seminar Series (with clinical fellows and K12 faculty), attendance at an Interdisciplinary Tumor Board, Clinical Case Report presentations to undergrads, and shadowing of physician- scientists. Taken together, training in the CBTG will provide the fundamental skills necessary for outstanding careers in biomedical cancer research, together with a deep appreciation of the challenges and complexity of cancer in the clinical setting.

NIH Research Projects · FY 2026 · 1986-04

The Multicenter Network of Neonatal Intensive Care Units (NRN) was established in 1986 to rapidly design, conduct, and publish studies in high priority areas. Case Western Reserve University (CWRU) is one of only two centers that has been part of the NRN, and contributed to its impact on the health of infants, since 1986. We enthusiastically look forward to the prospect of continuing our participation in the NRN. We will demonstrate that we continue to unquestionably meet all the requirements for inclusion as a clinical center. Our personnel are unparalleled in their expertise and productivity, as evidenced by our high enrollment rates and follow-up rates which typically exceed 90%. Our dedicated personnel recruit 24/7 including nights, weekends, and holidays. Our medical and nursing staff wholeheartedly believe that patient care is improved through research, encourage families to participate, and are committed to rigorous adherence to protocols. As the only level III/IV NICU in our health system with essentially no back transport, high risk mothers and infants are concentrated at our center and we are ideally poised to enroll and follow high risk mothers and infants in clinical trials. This includes an ideal setting for antenatal consent or consent in the first 24 hours after birth. Our team has a proven track record for recruiting and retaining diverse populations, and a long-standing commitment to research that will improve NICU care for all infants. We have a full complement of pediatric subspecialists who are supportive of the NRN and enthusiastic to participate in trials. CWRU investigators have shown themselves to be collaborative with other centers, and have assumed leadership roles in the NRN. We have set the standard for long term follow-up. CWRU has consistently enhanced the productivity of the NRN in every cycle by mentoring new centers to enable them to rapidly implement NRN procedures and protocols. The NRN has strong support from the CWRU School of Medicine, University Hospitals Rainbow Babies and Children’s Hospital (RBC) and MacDonald Women’s Hospital, The Departments of Pediatrics and Reproductive Biology, and the Divisions of Neonatology and Maternal Fetal Medicine. In the next cycle of the NRN we will continue to lead and innovate.

Other NSERC · FY 2024

brain, spinal cord, motor cortex, cerebellum, muscle, locomotion, neural recordings, electromyography, optogenetics, movement