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PROJECTS TO COVER BRAIN TUMOR, CEREBRAL EDEMA AND GASTROESOPHAGEAL CANCER RESEARCH

Three University Hospitals (UH) and �ǿմ�ý School of Medicine research teams recently received Collaborative Science Pilot Awards. The teams each received $50,000, funded by both institutions. If substantial progress is accomplished and milestones are achieved, an additional year of funding will be considered.

“Supported by the UH-�ǿմ�ý Joint Strategic Leadership Committee, the Collaborative Science Pilot Awards aim to inspire innovative and interdisciplinary research projects between the two institutions,” said Daniel I. Simon, president, and academic external affairs and chief scientific officer at UH and the Ernie and Patti Novak Distinguished Chair in Healthcare Leadership. “Since our new affiliation agreement enacted in 2021, there has been the formation of research working groups between UH Clinical Chairs and the School of Medicine’s Basic Science Chairs. We are excited to work together to help teams develop research projects and increase their competitiveness and capacity for major external funding opportunities.”

“In alignment with strategic research priorities and strength, the two institutions jointly formed five groups focused on five key research areas: infection, immune response and immunotherapy; cancer; brain health; genetics, genomic, genetic therapeutics; and health services research,” said Robert A. Salata, the John H. Hord Professor and Chairman at the School of Medicine and the UH Physician-in-Chief at the UH Cleveland Medical Center. “Each group is chaired by leaders in the clinical and basic sciences departments in order to help guide and support research.”

“Decisions on these awards were made based on significance, originality, scientific merit; experience and capability of the proposing faculty; relevance to collaborative science leading to a strong federal grant application; ability to carry out proposed research in one year; as well as budget justification and milestone,” said Stan Gerson, dean and Senior Vice President for Medical Affairs at the School of Medicine. “We received a number of competitive proposals. Following a rigorous peer-reviewed evaluation process, three meritorious proposals were identified for support. We look forward to seeing the discoveries these teams make.”

Award Teams and Project Descriptions:

1. Novel immunotherapies targeting a unique biomarker in the tumor microenvironment
   Susann Brady-Kalnay (Dept. of Molecular Biology and Microbiology) and David Wald (Dept. of Pathology)
   Brain tumors are one of the deadliest forms of cancer, including both primary brain cancer and tumors that metastasize to the brain. The highest-grade primary brain tumor, grade 4 glioma or glioblastoma (GBM), has a median survival of one year. Furthermore, tumors that metastasize to the brain also have very poor outcomes due to paltry therapeutic options. In this proposal, the team plans to develop novel immunotherapies for brain tumors. Previously, they developed peptides and protein fragments that bind to a novel tumor biomarker (PTPmu) and label both the primary mass and distant invasive cells. These reagents can be integrated into chimeric antigen receptors and utilized to direct T cells or NK cells to specifically kill tumors. By combining the targeting potential of PTPmu with the body’s own immune recognition, it is hypothesized that the PTPmu-targeted agents will trigger a systemic immune response and destroy these recalcitrant primary and metastatic brain tumors.
2. Bradykinin Formation in Malaria Cerebral Edema
   Alvin Schmaier (Dept. of Medicine) and James Kazura (Dept. of Pathology)
   The team will test their hypothesis that the local production of bradykinin is a proximal event in the development of brain swelling and death in cerebral malaria. The award will be used to develop a state-of-the-art mass spectroscopy assay to measure bradykinin in disease samples. It will be tested with samples from the murine model of cerebral malaria, with the goal to perform the same analysis on blood samples from African children with the disease.
3. Natural Killer Cells in Combination with TGFbeta Targeted Therapies in Gastroesophageal Cancer
   Andrew Blum (Dept. of Medicine), Eva Selfridge (Dept. of Medicine), David Wald (Dept. of Pathology), Kishore Guda (Case Comprehensive Cancer Center)
   Cancers of the esophagus and stomach are a major health problem and leading cause of cancer deaths. Treatment for these cancers often does not work well, and the development of effective therapies is an urgent, unmet clinical need. Natural Killer (NK) cell-based therapies are one promising approach. The team will test if blocking the TGFbeta signaling pathway can improve the effectiveness of NK cell based therapies for these cancers.   

For more information, contact Bill Lubinger at william.lubinger@case.edu.