Peter Storz, Ph.D.

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SUMMARY

Research in the Tumor Development, Immunology and Progression Laboratory of Peter Storz, Ph.D., focuses on the development and progression of pancreatic ductal adenocarcinoma. Dr. Storz's research goals are to develop liquid biopsy-based early detection methods, to identify new targets for therapy and to develop new individualized treatments for patients.

Focus areas

• Cell reprogramming as a cause of pancreatic disease. After tissue injury and inflammation, pancreatic acinar cells undergo reprogramming that changes them to a premature, ductlike phenotype. This process is called acinar-to-ductal metaplasia. In the presence of an oncogenic KRAS mutation, cells that have undergone acinar-to-ductal metaplasia progress to pancreatic intraepithelial neoplasia and eventually pancreatic cancer.

  Dr. Storz's lab is focused on understanding the mechanisms that drive such reprogramming of primary pancreatic acinar cells. A specific emphasis is on the cross talk of pancreatic cells with the innate immune system, and on KRAS-initiated signaling pathways. For these studies, the Storz laboratory uses transgene and knockout animal models, 3D explant organoid culture of primary cells, and viral delivery systems. The research team correlates data to patient tissue and liquid biopsy exams. The premise is that a better understanding of processes that drive lesion formation and progression will lead to both the development of early detection methods and new treatment methods for pancreatic ductal adenocarcinoma.

• Reactive oxygen species as drivers of pancreatitis and pancreatic cancer. Reactive oxygen species have multiple functions within cells, such as regulating cell proliferation, senescence and death. The Storz laboratory is interested in events that are regulated by reactive oxygen species and lead to pancreatic tumor initiation and progression.

  Mitochondria are known to generate reactive oxygen species in response to many stressors, and mitochondrial dysfunction is a common phenotype in cancer. Research in Dr. Storz's laboratory has shown that mitochondrial generation of reactive oxygen species is common to all inducers of acinar-to-ductal metaplasia. Further, the lab has identified protein kinase D1 (PKD1)-NF-κB and Notch signaling as the key signaling events in inflammation and cell death.

  The lab's current focus is on identifying mechanisms by which reactive oxygen species are generated in response to KRAS. The lab also is studying how PKD1 is targeted to the mitochondria, and the team is working to further refine the pathways PKD1 uses to drive acinar-to-ductal metaplasia. This project will improve the understanding of processes involved in pancreatitis and initiation of pancreatic cancer. The findings will allow the lab to test whether inhibitors of this pathway can efficiently target early lesions in pancreatitis and pancreatic ductal adenocarcinoma.

• Macrophage populations in pancreatic cancer. Pancreatic inflammation — also called pancreatitis — is a risk factor for pancreatic cancer.

  The Storz laboratory has shown that after acquisition of an oncogenic KRAS mutation, acinar cells start expressing chemoattractants for inflammatory macrophages, also called M1 macrophages. The research team found that once inflammatory macrophages are present in the pancreas, they initiate acinar-to-ductal metaplasia by secreting inflammatory cytokines such as tumor necrosis factor and regulated on activation, normal T cell expressed and secreted cytokine. In the presence of an oncogenic KRAS mutation, the resulting cells that have undergone acinar-to-ductal metaplasia then further progress to precursor lesions for pancreatic ductal adenocarcinoma, with a fibrotic, immunosuppressive microenvironment.

  The laboratory also has shown that this process is mediated by a phenotype switch toward alternatively activated macrophage populations, also known as M2 macrophages. This switch is induced by interleukin 13 secreted by a specific cell population within pancreatic intraepithelial neoplasia and cancer lesions.

  Dr. Storz's team is now using this knowledge to test treatment strategies that revert M2 macrophages to M1 macrophages. The overall goal of this work is to decrease fibrosis around precancerous and cancerous lesions, which would make them immunoreactive and responsive to chemotherapy.

Significance to patient care

Dr. Storz's lab develops ways to find pancreatic cancer early by screening patients' blood or saliva. The lab also develops individualized treatments for patients with pancreatitis or with pancreatic cancer that has spread, also known as metastatic pancreatic cancer.

Professional highlights

• Co-director, Pancreatic Cancer Group, Mayo Clinic in Florida, 2017-present.

• National Institutes of Health:

  • Standing member and co-chair, Biochemical and Cellular Oncogenesis Study Section, 2012-2023.

  • Standing member and co-chair, Molecular Oncogenesis Study Section, 2019-2022.

• Distinguished Investigator of the Year, Mayo Clinic in Florida, 2016.

• Member, Cellular and Molecular Medicine review panel, Department of Veterans Affairs, 2013.

• American Association for Cancer Research:

  • Member, Scientific Review Committee, Pancreatic Cancer Action Network Pathway to Leadership Grants, 2012.

  • Pancreatic Cancer Action Network Career Development Award, 2008.

• Member, Peer-Reviewed Cancer Research Program Discovery Award, Pancreatic Cancer-2 Panel, Department of Defense, 2011.

• Member, editorial board, International Scholarly Research Network Cell Biology, 2011.