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Scientific Accomplishments

Douglas McNeel, MD, PhD – Experimental Therapeutics Program

I/IIa clinical trial in 22 stage D0 prostate cancer patients was conducted to evaluate the safety of a DNA-based vaccine encoding Prostatic Acid Phosphatase (PAP).


PAP-specific CD4 (A) and CD8 (B) T-cell proliferation were monitored by flow cytometry as one measure of a potentially therapeutic immune response.


Nine out of 22 (41%) patients receiving the DNA vaccine exhibited PAP-specific increase in CD4 and/or CD8 T cell proliferation.

 

McNeel DG, Dunphy EJ, Davies JG, Frye TP, Johnson LE, Staab MJ, Horvath DL, Straus J, Alberti D, Marnocha R, Liu G, Eickhoff JC, Wilding G. Safety and immunological efficacy of a DNA vaccine encoding prostatic acid phosphatase in patients with stage D0 prostate cancer. Journal of Clinical Oncology. 2009;27(25):4047-54. PMCID: PMC2734418. Supported by NIH K56 RR16489, NIH/NCRR 1UL1RR025011 and DOD W81WXH-05-0404.

 

 

Jing Zhang, PhD - Cell Signaling Program

Flow cytometry demonstrated marked increase in myeloproliferative phenotypes, defined by myeloid markers Mac1 and Gr1 (A) and splenomegaly in the Nras knockin (NrasG12D/G12D) mice relative to Nras+/+ controls (C). Ki67 and DAPI stains and cell cycle analysis by flow cytometry demonstrated dose-dependent impact of oncogenic Nras expression on proliferation of bone marrow derived myeloid progenitors (B). Cell-cycle phases are defined by G0 (Ki67-, DAPIlo), G1 (Ki67+, DAPIlo) and S/G2/M (Ki67+, DAPIhi) (D). NrasG12D/+ mice ultimately succumbed to histiocytic sarcoma or a myeloproliferative disease that closely resembled CMML, whereas all NrasG12D/G12D mice died with acute myeloproliferative disease.

 

Figure A

Zhang Figure C

Wang J, Liu Y, Li Z, Wang Z, Tan LX, Ryu MJ, Meline B, Du J, Young KH, Ranheim E, Chang Q, Zhang J. Endogenous oncogenic Nras mutation initiates hematopoietic malignancies in a dose- and cell type-dependent manner. Blood. 2011;118(2):368-79. PMCID: PMC3138689. Supported by NIH/NCRR 1UL1RR025011.

 

 

Andreas Friedl, MD – Tumor Microenvironment Program

Stromal fibroblasts of breast carcinomas frequently express the cell surface proteoglycan syndecan-1 (Sdc1) and stromal Sdc1 expression correlates with an organized, parallel, extracellular matrix (ECM) fiber architecture (A, Left). Cell-free ECMs were generated from SDC-1positive and SDC-1negative murine and human mammary fibroblasts to determine the effect of this proteoglycan on invasion and migration of breast cancer cells (A, Right). Data generated using the BD Pathway microscope from the Flow Cytometry Lab showed that ECM containing SDC-1 in contrast to ECMs containing no SDC-1, promoted attachment, invasion and directional movement of MDA-MB-231 breast cancer cells (B).

 

 Figure A
Figure B

Yang N, Mosher R, Seo S, Beebe D, Friedl A. Syndecan-1 in breast cancer stroma fibroblasts regulates extracellular matrix fiber organization and carcinoma cell motility. The American Journal of Pathology. 2011;178(1):325-35. PMCID: PMC3069862. Supported by NCI R01CA107012.