Philip Streeter, Ph.D.
Dr. Streeter received his B.S. from the University of California-Davis in 1977. He attended graduate school at Kansas State University, receiving an M.S. in Laboratory Medicine in 1980 and a Ph.D. in Microbiology in 1985. Dr. Streeter continued his studies as a Postdoctoral Fellow in the Department of Pathology at Stanford University, investigating the molecular mechanisms involved in leukocyte recruitment to diverse lymphoid and extralymphoid tissues. In 1989 Dr. Streeter joined the biotechnology company SyStemix Inc., Palo Alto, CA, and moved to St. Louis, MO, in 1992 to work at Searle/Monsanto, now Pfizer. While working in these companies, Dr. Streeter led research efforts in the engineering of hematopoietic cytokines, the development of anti-tumor vaccines, and the identification of selective inhibitors of autoimmune disease. In 2000, Dr. Streeter joined Oregon Health & Science University and he is currently an Associate Professor in the Department of Medicine. In 2003 he became Director of the OHSU Hematopoietic Cell Processing Laboratory, and in 2004 he became a member of the Oregon Stem Cell Center, where he is Director of the Center's monoclonal antibody and flow cytometry core facilities and conducts independent research.
The long-term research goals of the Streeter laboratory are to contribute to the emerging fields of tissue engineering/repair and the development of tools for cancer diagnosis. Areas of research focus are beta cell replacement therapies for the treatment of diabetes, the identification of lung progenitor cell populations involved in lung repair, and in the diagnosis of pancreatic cancer.
Cellular replacement therapy using islets has been shown to be partially effective in the treatment of type I diabetes. However, the supply of donor-derived islets will never meet the needs of the large number of patients who could potentially benefit from this cell-based therapy. Stem/progenitor cells offer the promise that transplantable beta cells may be generated in the laboratory.
To deliver on that promise, our laboratory is collaborating with the laboratories of Markus Grompe, M.D., OHSU, and Gordon Keller, Ph.D., University Health Network, Toronto, Canada, in the development and characterization of monoclonal antibodies directed against cell surface molecules expressed by pancreatic cell subsets as well as pancreatic progenitor cells derived from pluripotent stem cells.
Reagents from this panel are anticipated to 1) enable progenitor cell isolation; 2) provide a means of monitoring the differentiation of beta cell precursor cells, such that cell culture conditions in the laboratory can be optimized to deliver desired cell products; and 3) facilitate the purification of cell culture expanded cell populations for cell-based therapies.
Lung Development and Repair
This project focuses on the compelling need to generate cell-surface marker specific reagents useful for identification, study, and isolation of pulmonary stem/progenitor cells. The lung contains a large number of diverse cell types that produce and maintain lung structure and function. Our limited understanding of the complex cellular composition, anatomy, and function of this tissue has slowed the establishment of effective tissue regenerative (repair) and/or cell replacement (transplantation) therapies.
Our laboratory, in collaboration with the laboratory of Jeffrey Whitsett, M.D., at the Cincinnati Children's Hospital, is generating and characterizing a panel of monoclonal antibodies targeting cell-surface markers on different subsets of pulmonary cells involved in the process of pulmonary tissue regeneration. Characterization of these novel reagents is being performed using multiple model systems of lung repair/regeneration.
Pancreatic ductal adenocarcinoma is the most common form of pancreatic cancer and it is the most lethal of all solid cancers. In the USA approximately 32,000 people are diagnosed every year with pancreatic ductal adenocarcinoma, and the five-year survival rate following initial diagnosis is extremely low, at just 1 to 5%. A primary reason for the low survival rate for patients with pancreatic adenocarcinoma is the inability to diagnose this cancer during early stage disease. At present, only 15% of newly diagnosed patients are diagnosed with early stage disease.
Our laboratory, in collaboration with Dr. Brett Sheppard, M.D., of OHSU, has focused on development of reagents that will facilitate early diagnosis and/or treatment of pancreatic cancer. One recently developed reagent recognizes a molecule associated with human pancreatic cancer cells as well as precancerous lesions of the pancreas. The molecule is not produced by normal human pancreatic cells or by cells from patients with inflamed pancreas. These results suggest that this reagent can be used as a diagnostic reagent for pancreatic cancer, and that the molecule targeted by this reagent is a biomarker of this disease.
Current research efforts are to further validate this reagent in the diagnosis of pancreatic cancer and to develop a rapid and non-invasive diagnostic screening assay for this devastating disease.
1. PR Streeter, NI Minster, LE Kahn, WF Hood, LE Vickery, TL Thurman, JB Monahan, JK Welply, JP McKearn, and SL Woulfe. Progenipoietins: biological characterization of a family of dual agonists of fetal liver tyrosine kinase-3 and the granulocyte colony-stimulating factor receptor. Exp Hematol. 2001. 29:41-50.
2. WH Fleming, JM Mulcahy, JP McKearn, and PR Streeter. Progenipoietin mobilizes substantial numbers of transplantable hematopoietic stem cells. Exp Hematol 2001. 29:943-51.
3. PR Streeter, LZ Dudley, and WH Fleming. Activation of the G-CSF and Flt-3 receptors protects hematopoietic stem cells from lethal irradiation. Exp Hematol. 2003. 31:1119-25.
4. PR Streeter, X Zhang, TV Tittle, CN Schon, AD Weinberg, RT Maziarz. CD25 expression distinguishes functionally distinct alloreactive CD4 CD134 (OX40) T-cell subsets in acute graft-versus-host disease. Biol Blood Marrow Transplant. 2004. 10:298-309.
5. C Dorrell, SL Abraham, KM Lanxon-Cookson, PS Canaday, PR Streeter, M Grompe. Isolation of major pancreatic cell types and long-term culture-initiating cells using novel human surface markers. Stem Cell Research. 2008. 1:183-194.
6. C Dorrell, L Erker, KM Lanxon-Cookson, SL Abraham, T Victoroff, S Ro, PS Canaday, PR Streeter, M Grompe. Surface Markers for the Murine Oval Cell Response. Hepatology. 2008. 48:1282-1291.
7. M Kovacsovics-Bankowski, K Mauch, A Raber, PR Streeter, R Deans, RT Maziarz, W van't Hof. Pre-Clinical Safety Testing Supporting Clinical Use of Allogeneic Multipotent Adult Progenitor Cells. Cytotherapy. 2008. 10:730-42.
8. S Jiang, A Bailey, D Goldman, J Swain, M Wong, PR Streeter, WF Fleming. Hematopoietic Stem Cells Contribute to Lymphatic Endothelium. PLos ONE. 2008. 3:e3812.
9. M Kovacsovics-Bankowski, PR Streeter, K Mauch, A Raber, Wouter Vant Hof, R Deans, RT Maziarz. Clinical Scale Expanded Adult Pluripotent Stem Cells Prevent Graft-Versus-Host Disease. Cell Immunol. 2009. 255:55-60.
10. Gadue P, Gouon-Evans V, Cheng X, Wandzioch E, Zaret KS, Grompe M, Streeter PR, Keller GM. Generation of monoclonal antibodies specific for cell surface molecules expressed on early mouse endoderm. Stem Cells. 2009. 27:2103-13.
11. HD Adkisson, C Milliman, X Zhang, RT Maziarz, PR Streeter. Immune evasion by neocartilage-derived chondrocytes: Implications for biologic repair of joint articular cartilage. Stem Cell Res. 2010. 4:57-68.
12. HD Adkisson, JA Martin, RL Amendola, C Milliman, KA Mauch, AB Katwal, M Seyedin, A Amendola, JA Buckwalter, PR Streeter. The Potential of Human Allogeneic Juvenile Chondrocytes for Restoration of Articular Cartilage. Am J Sports Med. 2010. (Epub ahead of print).