CLEVELAND– In the spirit of encouraging and more rapidly advancing team science among clinical and basic science faculty, University Hospitals and the Case Western Reserve University School of Medicine have jointly funded five committed research teams 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 opportunity to receive additional funding as substantial research progress is made and that scientific steps are taken. Established two years ago, the awards program aims to inspire innovative research projects across UH and Case Western Reserve. The awards leverage the evolution of scientific endeavors in which research moves to teams, fostering collaboration to more effectively advance science in important ways.
“The goal of this joint effort is to bring together physician-scientists and scientists to solve unmet clinical needs. We have world-class faculty at UH and CWRU who are eager to collaborate and advance science,” said Daniel I. Simon, MD, president of academic and external affairs and chief scientific officer at UH and holder of the Ernie and Patti Novak Distinguished Chair in Healthcare Leadership. “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.” »
Second round of pilot funding allows more team-based research to take root and grow
The funding awarded in late 2024 builds on an initiative launched in 2023 when UH and the Case Western Reserve School of Medicine formed five groups focused on five key research areas: infection, immune response, immunotherapy; cancer; brain health; genetics, genomics, genetic therapy; and health services research. In 2024, a record number of research teams submitted proposals that were evaluated by a scientific committee composed of leading researchers.
After a rigorous peer review process, the five meritorious proposals identified for support included the following projects:
- Organizing and curating a large-scale UH MR fingerprint database: first steps toward a multi-institutional MR fingerprint consortium. Team: Chaitra Badve, MD (radiology) and Mark Griswold, PhD (biomedical engineering)
UH and Case Western Reserve have been pioneers in implementing the highly promising MR fingerprint imaging technology into direct patient care. As part of this initiative, the team is developing the world’s first quantitative MRI fingerprint neuroimaging database on a large population. The proposed 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, unique infrastructure, and synergistic expertise toward a broader vision of a multi-institutional MRI fingerprint consortium to accelerate the development of generalizable, well-validated biomarkers in various neurological diseases.
- Help with genetic risks for the early detection of keratoconus. Team: Sudha Iyengar, PhD (Population and Quantitative Health Sciences) and Loretta Szczotka-Flynn, DO, PhD (Ophthalmology)
Keratoconus is a corneal thinning disease that usually manifests in the second or third decade of life, leading to corneal irregularity and decreased visual acuity. Early diagnosis followed by subsequent treatment with corneal collagen cross-linking can prevent vision loss. No single test can reliably diagnose keratoconus in its early stages. The team aims to develop an accurate genetic test for keratoconus, a polygenic risk score, to complement current diagnostic tests and support early intervention. This project will allow them to produce a set of genetic biomarker tools capable of predicting keratoconus, then validate the overall 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 disease treatment by small molecule inhibitors of 15-PGDH. Team: Stephen Fink, PhD (Case Comprehensive Cancer Center) and Andrew Pieper, MD, PhD (psychiatry)
Worldwide, more than 55 million people currently suffer from dementia caused by neurodegenerative diseases, such as Alzheimer’s disease (AD), for which there is no basic treatment. The team identified the 15-PGDH protein as a novel therapeutic target in AD by demonstrating that 15-PGDH inhibition prevents neurodegeneration and preserves cognition in an AD mouse model. They plan to use gene expression analysis of myeloid cells, the cell population found in the brain to highly express 15-PGDH, to determine the in vivo pathways by which pharmacological inhibition of 15-PGDH prevents the development of neuropathology and cognitive deficit in an AD mouse. model.
- A probiotic approach to treating gastrointestinal symptoms associated with autism spectrum disorders. Team: Mahmoud Ghannoum, PhD (Dermatology), Grace McComsey, MD (Pediatrics and Medicine), Masaru Miyagi, PhD (Pharmacology) and Thomas McCormick, PhD (Dermatology)
Autism spectrum disorder (ASD) is a complex developmental disorder associated with comorbidities including anxiety, neuropsychiatric symptoms, immune dysregulation, and gastrointestinal (GI) abnormalities. Preliminary profiling of the gastrointestinal microbiome of ASD patients revealed polymicrobial bacterial and fungal imbalances that the team believes lead to the formation of intestinal biofilms contributing to the pathogenesis and gastrointestinal symptoms often associated with ASD. To address this issue, the team proposes testing the potential of a probiotic amylase supplement designed to treat polymicrobial dysbiosis and biofilm formation in a clinical study aimed at improving gastrointestinal symptoms in ASD patients.
- Bradykinin formation in cerebral edema due to malaria. This research project is receiving funding for the second year and is led by Alvin Schmaier, MD (medicine) and James Kazura, MD (pathology).
During the first year of support, the team proved their hypothesis that local production of bradykinin is a proximal event in experimental cerebral malaria. This work was carried out by using murine genetic knockout mice of each protein of factor XII and the plasma kallikrein/kinin system and by the development of an LCMSMS assay to measure bradykinin in murine plasma. Currently, the team has identified a therapeutic agent that recapitulates the protection against cerebral malaria observed in prekallikrein KO mice. This agent, a plasma kallikrein inhibitor, rescues dying infected mice at late stages of disease progression and serves as an adjuvant to concomitant antiparasitic therapy. Current efforts in the second year of support aim to translate these research findings into a program to develop plasma kallikrein inhibitors as an adjunctive treatment for cerebral malaria in humans.
Mobilization of human and financial resources has the power to transform medicine
Historically, team science and the mobilization of human and financial resources have contributed to groundbreaking research and scientific advancements across the UH Case Western Reservation. Over time, such advances not only expand the realm of scientific knowledge and applications, but also transform medical care in various patient care settings, thereby improving clinical outcomes and overall community health.
Programs such as the Collaborative Science Pilot Awards enable researchers to pursue the research necessary to validate and support the process of scientific discovery to ultimately develop cutting-edge diagnostics, therapies and procedures.
“Collaboration and mentoring are essential to the advancement of science, innovation and medicine,” said Stanton L. Gerson, MD, dean and senior vice president for medical affairs, School of Medicine; Director of the National Center for Regenerative Medicine at Case Western Reserve; Asa and Patricia Shiverick – Jane Shiverick (Tripp), professor of hematologic oncology; and Professor Emeritus at Case Western Reserve University. “We are very pleased to see more proposals submitted together this year from principal investigators and early career faculty. The interdisciplinary mentoring and collaboration that shines through in research and clinical enterprises facilitates problem solving, enables challenges to be addressed, and provides the support and guidance necessary for researchers at all career levels to thrive.
In the future, the germination of science and innovation enabled by pilot grants will redefine the standard of care across multiple medical specialties and patient care settings.