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COLLABORATORS
RUSTY JONES, Ph.D.
Van Andel Research Institute
Dr. Russell Jones is a leading expert in cancer metabolism and immunology. As professor and program lead of the Metabolic and Nutritional Programming group at Van Andel Research Institute, his work seeks to uncover how cancer cells fuel themselves through metabolic interactions, with the ultimate goal of developing new cancer therapeutics.
Despite significant advances in precision medicine and immuno-oncology, lung cancer patients with KRAS mutations still face poor outcomes. Cancer cells resist treatment by leveraging alternative survival pathways to meet their energy demands and fuel their growth. In this proposal, the MacKeigan and Jones laboratories are collaborating to inhibit the autophagy pathway in preclinical models of lung cancer and dissect the metabolic changes in tumors and immune cells, which will help inform new treatment strategies for patients with advanced lung cancer.
R01CA297993
Michigan State University
Dr. Ellsworth directs the MSU Medicinal Chemistry Facility and has over 25 years of experience as a synthetic and medicinal chemist. The lab is working with Dr. Ellsworth to develop small molecule inhibitors to target the autophagy pathway. Targeting the autophagy pathway may prove beneficial in treating cancers already resistant to current therapies. This work is important because existing autophagy inhibitors lack specificity, resulting in off-target effects. We aim to develop an autophagy inhibitor with drug-like properties for future preclinical studies and possible therapeutic development.
Cincinnati Children’s Hospital Medical Center
Dr. Krueger is an expert TSC clinician and researcher, and we are working with him to sequence TSC patient samples and analyze the resulting genomic data. TSC affects each patient differently, with some patients being symptom-free and others experiencing severe tumor burden and clinical manifestations. This research with Dr. Krueger’s team will determine whether genomic data can explain varying levels of disease severity in patients, and may inform personalized treatment strategies.
Henry Ford Health
Howard Crawford is the Scientific Director of the Henry Ford Health + Michigan State University Pancreatic Cancer Center. The Crawford and MacKeigan lab’s collaborative research centers on the pancreatic tumor microenvironment, with emphasis on how cancer cells and stromal and immune cells communicate to promote tumor growth, invasion, and metastasis. Their work focuses on inhibiting autophagy in pancreatic cancer, highlighting pathways that support therapy resistance and immune evasion.
Michigan State University
In partnership with Dr. Sortwell, we are investigating the potential of Rho kinase inhibitors as a treatment for Parkinson’s Disease (PD). Dr. Sortwell’s lab has significant expertise using preclinical models of PD, while our team brings strong skills in kinase assays to validate target engagement. This project aims to uncover whether existing drugs or compounds may be repurposed for treatment in PD.
Van Andel Research Institute
Our laboratory is working to evaluate ULK-101, our novel ULK1 inhibitor, in preclinical models of lung cancer. Dr. Williams has over 25 years of experience working with mouse models of cancer. As such, Dr. Williams and his lab provide important insights and expertise as we test our compound in genetically engineered models (GEMM) of KRAS-driven lung cancer. These studies will provide data to support the safety, efficacy, and target engagement of ULK-101 in mammalian models, thereby laying a foundation for future clinical development of this compound and other autophagy inhibitors.