Canada Research Chair in Cancer Therapy Resistance
Professor, Dept. of Urologic Sciences
Faculty of Medicine University of British Columbia
Senior Scientist
Vancouver Prostate Centre

Dr. Zoubeidi’s research program aims to provide mechanistic insight into the molecular (genetic and epigenetic) sources that fuel tumor cell plasticity and emergent resistance phenotypes following targeted therapy. In this seminar, Dr. Zoubeidi will discuss lineage plasticity in treatment resistance prostate cancer.  She will discuss how she leverages this information and this knowledge to identify early detection biomarkers and nominate new targets to block the mechanisms utilized by tumor cells to gain access to cell plasticity that can be used alone or in combination to improve the efficacy of existing therapies and patient outcomes. Importantly, as lineage reprogramming is emerging as a conserved mechanism of resistance across tumor types, results from this program may have relevance in other highly prevalent cancers, such as melanoma and lung and breast cancer.

Professor
Karmanos Cancer Institute
Wayne State University

Although major oncogenes and tumor suppressor genes have been identified, there remains great variation in cancer occurrence and reoccurrence even within the same category of disease. Dr. Wei hypothesized that selected molecules in the tumor microenvironment regulate oncogene induced cancer. To test this hypothesis, “we seek breast cancer regulatory genes using Diversity Outbred (DO) F1 mice that express NeuT or d16HER2 oncogene in individually unique genetic background.” A splice variant of human HER2 with exon 16 truncation, d16HER2 is expressed in most HER2+ tumors and has been associated with aggressive disease. Together, NeuT and d16HER2 Tg mice represent the full spectrum of HER2 induced tumors. DO mice were generated by non-sibling crossing of 8 inbred founder strains (A/J, C57BL/6J, 129S1/SvlmJ, NOD/HILtJ, NZO/HiLtJ, CAST/EiJ, PWK/PhJ and WSB/EiJ). DO F1 mice mimic the heterogeneous outbred human patients, but carry custom designed mosaic genomes. High resolution linkage between phenotypes and genotypes is made possible by analyzing the >45 million single nucleotide polymorphism (SNP) harbored in DO mice. Dr. Wei has established the path for identifying candidate genes, validating their clinical relevance, and interrogating their functional pathways. Using scRNA sequencing, the researcher has further defined the cell types that express the candidate genes.  New intervention strategies targeting these cells are being developed singly or in combination with conventional therapy. The DO F1 functional genomics platform is an efficient tool for finding a needle in a haystack quickly and accurately.

University Professor
George and MaryLou Boone Chair in Craniofacial Biology
Director, Center for Craniofacial Molecular Biology
Ostrow School of Dentistry
University of Southern California

Dr. Chai will discuss recent scientific advances in craniosynostosis. Infants born with craniosynostosis have skull dysmorphology, increased intracranial pressure (ICP), and cognitive impairment, compromising quality of life. Animal models recapitulating these phenotypes are lacking. The speaker will show that Twist1^+/- mice with craniosynostosis have increased ICP and neurocognitive behavioral abnormalities, recapitulating features of human Saethre-Chotzen syndrome. Furthermore, citalopram is a selective serotonin reuptake inhibitor (SSRI), which is the most commonly prescribed class of antidepressant drugs. Maternal SSRI usage is also known as an environmental risk factor for craniosynostosis in humans. Dr. Chai will discuss a preliminary study showing that Twist1 mutation may interplay with citalopram in exacerbating skull and neurocognitive defects in craniosynostosis. Using a biodegradable material combined with mesenchymal stem cells (MSCs), researchers successfully regenerated a functional cranial suture that recruited endogenous MSCs, corrected skull deformity, normalized ICP, and rescued neurocognitive behavior deficits. MSC-based cranial suture regeneration offers a paradigm shift in treatment to reverse skull and neurocognitive abnormalities in this devastating disease.