University Hospitals and Case Western Reserve University Collaborative Science Pilot Awards Infuse $250,000 to Accelerate Five Promising Research Projects

CLEVELAND -- In the spirit of encouraging and more rapidly advancing team science between clinical and basic science faculty, University Hospitals and Case Western Reserve University School of Medicine have 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 UH and Case Western Reserve. The awards leverage the evolution of scientific endeavors in which research is shifting to teams, promoting collaboration to more effectively move science forward in important ways.

"The purpose of this joint effort is to bring physician-scientists and scientists together to solve unmet clinical needs. We have world-class faculty at both UH and CWRU that are eager to collaborate and advance science," said Daniel I. Simon, MD, President of Academic & External Affairs and Chief Scientific Officer at UH and 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."

A Second Round of Pilot Funding Allows More Team Research to Take Root and Grow

The funding awarded in late 2024 builds upon an initiative launched in 2023 when UH and Case Western Reserve School of Medicine formed five groups focused on five key research areas - infection, immune response, immunotherapy; cancer; brain health; genetics, genomic, genetic therapeutics; and health services research. In 2024, a record number of research teams submitted proposals which were evaluated by a scientific committee comprised of leading investigators.

After a rigorous peer-reviewed evaluation process, the five meritorious proposals identified for support included the following projects:

1. Organizing and Curating Large-Scale UH MR Fingerprinting Database: First Steps Towards Multi-Institutional MR Fingerprinting 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 Fingerprinting imaging technology in direct patient care. Under this initiative, the team is developing the world's first MR Fingerprinting Quantitative Neuroimaging Database in 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 their global leadership, unique infrastructure and synergistic expertise towards a larger vision of a Multi-institutional MR Fingerprinting Consortium to accelerate development of generalizable, well-validated biomarkers in various neurological diseases.
   
   

2. A Genetic Risk Aid for Early Keratoconus Detection. Team: Sudha Iyengar, PhD (Population and Quantitative Health Sciences) and Loretta Szczotka-Flynn, DO, PhD (Ophthalmology)

   Keratoconus is a corneal thinning disease typically presenting in the second or third decade of life, which causes corneal irregularity and reduced visual acuity. Early diagnosis with subsequent treatment with corneal collagen crosslinking can prevent vision loss. No single test can reliably diagnose keratoconus in its earliest stages. The team aims to develop an accurate genetic test for keratoconus, a Polygenic Risk Score, to complement current diagnostic tests and drive early intervention. This project will enable them to produce a toolset of genetic biomarkers capable of predicting keratoconus and then validate the overall model in existing biobank cohorts as well as a new local dataset from UH Cleveland Medical Center.
   
   

3. Single-cell RNA Sequencing Analysis of the Mechanism of Alzheimer's 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 are currently suffering 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, 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.
   
   

4. A Probiotic Approach to Treating Gastrointestinal Symptoms Associated with Autism Spectrum Disorder. 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 GI microbiome profiling of ASD patients yielded polymicrobial bacterial and fungal imbalances that the team hypothesizes results in formation of intestinal biofilms contributing to the pathogenesis and GI symptomologies often associated with ASD. To address this, the team proposes to 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.
   
   

5. Bradykinin Formation in Malaria Cerebral Edema. This research project is receiving a second year of funding and is led by Alvin Schmaier, MD (Medicine) and James Kazura, MD (Pathology).
   In 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 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. Presently, the team has 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. Current efforts in year two of support is to turn these research findings into a program for development of plasma kallikrein inhibitors as adjunctive therapy for human cerebral malaria.

The Mobilization of Human and Financial Resources Holds the Power to Transform Medicine

Historically, team science and the mobilization of human and financial resources have contributed to groundbreaking research and scientific advancement throughout UH Case Western Reserve. Over time, such strides not only expand the realm of scientific knowledge and application, but they also transform medical care across diverse patient care settings, improving clinical outcomes and elevating community health overall.

Programs like the Collaborative Science Pilot Awards enable 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.

"Collaboration and mentorship are essential for 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 Hematological Oncology; and Case Western Reserve Distinguished University Professor. "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."

Moving forward, the germination of science and innovation the pilot awards make possible will redefine the standard of care across multiple medical specialties and patient care settings.