Address421 E. Canfield Street, Suite 2226 Detroit, MI 48201
Barbara Ann Karmanos Cancer Institute
421 E. Canfield Street, Suite 2226
Detroit, MI 48201
DepartmentBarbara Ann Karmanos Cancer Institute
• Prevent cancer occurrence or relapse by active immunization
• Identify critical molecules, cells and mechanisms that regulate cancer progression and tumor immunity through genetic and transcriptomic analysis
• Test new strategies to prevent cancer progression based on novel genetic and transcriptomic findings.
Cancer vaccines developed in our lab have advanced to clinical trials with positive findings. Much of our previous publications demonstrated the effort and results from this line of study. To further the benefit of such induced or endogenous anti-tumor immunity, we generated or incorporated several model systems to recapitulate cancer progression and tumor immunity in humans, including spontaneous mammary tumors induced by oncogene HER2/Neu or a more malignant HER2 splice variant d16HER2 which lacks exon 16, as well as patient-derived xenografts (PDX). We incorporated Diversity Outbred (DO) mice into the spontaneous tumor progression model to mimic the individually unique genetic compositions of humans. We use the “R” based mouse Quantitative Trait Locus (QTL) algorithm to link individual mouse genome to their tumor onset time, response to active immunization (Manuscript under review) and other immunological parameters. This technology enables the identification of genetic loci that influence the phenotypes of interest. The genes that contribute to such influence and the cell types that carry out such influence are exploited to elevate endogenous or immunization induced anti-tumor immunity.
To dissect the changes that take place during the transition from normal mammary tissue to a clinically detectable tumor, we display the RNA profiles at every stage of the disease progression using single cell transcriptomics analysis (scRNA seq). Changes in the myeloid and lymphoid cells are revealed during the transition from microscopic to macroscopic lesions. The distinct phenotypic changes have opened many opportunities for scientific and interventional studies. Furthermore, the genes discovered through DO QTL studies are vetted in scRNA seq profiles to validate the importance of the genes and to define the interaction of suspect genes/cells. Much remains to be discovered with the new technologies at this very exciting time for tumor immunology and immunotherapy research.
Jones, RF., Reyes, JD., Gibson, HM., Jacob, JB., Vaishampayan, U., Ratner, S., Chen, K., and Wei, WZ. An HER2 DNA vaccine with evolution-selected amino acid substitutions in HER2 transgenic mice reveals a fundamental principle for cancer vaccine formulation. Cancer Immunology and Immunotherapy. 2019;68:1143-55.
An, W., Yu, C., Xi, J., Reyes, J., Mao, G., Wei, WZ. and Liu, H. Induction of necrotic cell death and activation of STING in the tumor microenvironment via cationic silica nanoparticles leading to enhanced antitumor immunity. Nanoscale. 2018;10:9311-9.
Veenstra, J., *Gibson, HM., Littrup, PJ., Reyes, JD., Cher, ML., Takashima, A. and Wei WZ. Cryotherapy with concurrent CpG oligonucleotide treatment controls local tumor recurrence and modulates Her2/neu immunity. Cancer Res. 2014;74:5409-20.
Aurisicchio, L., Peruzzi1, D., Koo, G., Wei, WZ., La Monica, N. and Ciliberto1, G. Immunogenicity and therapeutic efficacy of a dual component Genetic Cancer Vaccine Co-Targeting CEA and HER2/neu in preclinical models. Hum Gene Ther. 2013;25:121-31.
Norell, H., Poschke, I., Charo, J., Wei, WZ., Erskine, C., Piechocki, MP., Knutson, KL., Kiessling R., Lidbrink, E. and Bergh, J. Vaccination with a plasmid DNA encoding HER-2/neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma: a pilot clinical trial. J. Translational. Med. 2010;8:53.
BS in Plant Pathology (1973): National Taiwan University, Taipei, Taiwan
MS in Medical Microbiology (1975): Upstate Medical Center, State University of New York, Syracuse, New York
PhD in Biology (1978): Brown University, Providence, Rhode Island
CB7300 Special Topics F31 Grant Writing Course