To encourage and advance team science between clinical and basic science faculty, Case Western Reserve University School of Medicine and University Hospitals (UH) jointly funded five research teams engaged in new and promising scientific studies.
The Collaborative Science Pilot Awards, a program supported by the CWRU-UH Joint Strategic Leadership Committee, recently awarded each team $50,000 with the possibility of receiving additional funding as substantial research progress is made and scientific milestones are met.
Established two years ago, the awards program aims to inspire innovative research projects across Case Western Reserve and UH. The awards leverage the evolution of scientific endeavors in which research is shifting to teams, promoting collaboration to more effectively move science forward.
“Collaboration and mentorship are essential for the advancement of science, innovation and medicine,” said Stan Gerson, dean and senior vice president for medical affairs at the School of Medicine and director of the National Center for Regenerative Medicine at Case Western Reserve. “We are very pleased to see more proposals submitted by senior investigator and early-career faculty together this year. The interdisciplinary mentorship and collaboration that transpires across research and clinical enterprises facilitates problem-solving, enables the navigation of challenges and provides the support and guidance necessary for researchers at all career levels to thrive.”
The funding awarded in late 2024 builds on an initiative launched in 2023 when the School of Medicine and UH formed five groups focused on five key research areas: infection, immune response and immunotherapy; cancer; brain health; genetics, genomic and genetic therapeutics; and health services.
A scientific committee of leading investigators evaluated a record number of proposals submitted by research teams last year. The five projects identified for support:
Organizing and curating large-scale MR fingerprinting database: First steps toward multi-institutional MR fingerprinting consortium
Team: Chaitra Badve, an associate professor of radiology at the School of Medicine and radiology physician and director of MRI at UH; and Mark Griswold, the Pavey Family Designated Professor of Innovative Imaging-Revolutionizing the Worlds of Education at the School of Medicine and biomedical engineering at the Case School of Engineering
Case Western Reserve and UH have pioneered implementing magnetic resonance fingerprinting (MRF) imaging technology in direct patient care. The team is developing the world’s first MRF quantitative neuroimaging database in a large population. The project will focus on organizing and curating an MRF database for hypothesis driven sub-projects in various neurological diseases. The team will also leverage its global leadership, infrastructure and expertise toward a larger vision of a multi-institutional MRF consortium to accelerate development of generalizable, well-validated biomarkers in various neurological diseases.
A genetic risk aid for early keratoconus detection
Team: Sudha Iyengar, a professor and vice chair for research in the Department of Population and Quantitative Health Sciences at the School of Medicine; and Loretta Szczotka-Flynn, the Searle-Huang Professor in the Department of Ophthalmology and Visual Sciences at the School of Medicine, and director of the Vision Research Coordinating Center at the University Hospitals Cleveland Medical Center
Keratoconus is a corneal-thinning disease typically detected when someone is in their 20s or 30s that causes visual problems. Early diagnosis with subsequent treatment with corneal collagen “crosslinking” can prevent vision loss, but no test can reliably diagnose the disease in its earliest stages. The team aims to develop an accurate genetic test for keratoconus to complement current diagnostic tests and drive early intervention. The project will allow them to produce genetic biomarkers to predict keratoconus and validate the model in existing biobank cohorts as well as a new local dataset from UH Cleveland Medical Center.
Single-cell RNA sequencing analysis of the mechanism of Alzheimer’s treatment by small molecule inhibitors of 15-PGDH
Team: Stephen Fink, an associate professor at the Case Comprehensive Cancer Center, and Andrew Pieper, a professor of psychiatry and neurosciences at the School of Medicine and director of the Brain Health Medicines Center of the Harrington Discovery Institute at UH
Worldwide, more than 55 million people suffer from dementia caused by neurodegenerative conditions, such as Alzheimer’s disease (AD), for which there are no disease-modifying treatments. The team has identified the protein, 15-PGDH, as a novel therapeutic target in AD by demonstrating that inhibition of 15-PGDH prevents neurodegeneration and preserves cognition in an AD mouse model. They plan to employ gene- expression analysis of myeloid cells, the cell population found in the brain to highly express 15-PGDH. They hope to determine the in-vivo pathways by which pharmacologic 15-PGDH inhibition prevents the development of neuropathology and cognitive impairment in an AD mouse model.
A probiotic approach to treating gastrointestinal symptoms associated with autism spectrum disorder
Team: Mahmoud Ghannoum, a professor of dermatology and pathology at the School of Medicine, and director of the Center for Medical Mycology at UH; Grace McComsey, vice dean for clinical and translational research at the School of Medicine and research integrity officer at UH; Masaru Miyagi, a professor of pharmacology at the School of Medicine; and Thomas McCormick, an associate professor of dermatology at the School of Medicine
Autism Spectrum Disorder (ASD) is a complex developmental disorder associated with comorbidities including anxiety, neuropsychiatric symptoms, immune dysregulation and Gastrointestinal (GI) abnormalities. Preliminary GI microbiome profiling of ASD patients yielded polymicrobial bacterial and fungal imbalances that the team hypothesizes results in the formation of intestinal biofilms, contributing to the pathogenesis and GI symptomologies often associated with ASD. To address this, the team will test the potential for a probiotic amylase supplement designed to address polymicrobial dysbiosis and biofilm formation in a clinical study to improve gastrointestinal symptoms of ASD patients.
Bradykinin formation in malaria cerebral edema
Award represents a second year of funding; project is led by Alvin Schmaier, a professor of pathology at the School of Medicine and hematology and oncology physician at UH; and James Kazura, a Distinguished University Professor of pathology at the School of Medicine
In the first year of support, the team proved its hypothesis that local production of bradykinin is a proximal event in experimental cerebral malaria. The work was completed by using murine genetic knockout mice of every protein in the factor XII and plasma kallikrein/kinin system and by the development of a LCMSMS assay to measure bradykinin in murine plasma. The team recognized a therapeutic agent that recapitulates cerebral malaria protection observed in prekallikrein KO mice. This agent, a plasma kallikrein inhibitor, rescues moribund infected mice late in disease progression, serving as an adjuvant to concurrent anti-parasite therapy. With this new round of support, they hope to advance their research findings to develop plasma kallikrein inhibitors as adjunctive therapy for human cerebral malaria.
The program
Programs like the Collaborative Science Pilot Awards allow researchers to pursue the research needed to validate and sustain the process of scientific discovery to ultimately develop state-of-the-art diagnostics, therapies and procedures.
“The purpose of this joint effort is to bring physician-scientists and scientists together to solve unmet clinical needs,” said Daniel I. Simon, president of academic and external affairs and chief scientific officer at UH and the Ernie and Patti Novak Distinguished Chair in Healthcare Leadership. “We have world-class faculty at both UH and CWRU that are eager to collaborate and advance science. We look forward to working together once again this year to inspire teams to further develop their research, make new discoveries in their fields and increase their competitiveness for major external funding opportunities.”
