Seema Somji, Ph.D., Associate Professor
Project: Mechanisms of gene expression changes and squamous differentiation in a model of metal-induced bladder cancer
Mentor: Seema Somji, Ph.D., Associate Professor
Location: UND School of Medicine & Health Sciences, W432
Description: Cancer will affect about 40 percent of everyone and about 20 percent will eventually die from the disease. About 1/10th of this will be due to bladder cancer, which is a cancer highly linked to environmental exposure. This lab focuses on bladder cancer resulting from heavy metal exposure, particularly arsenic and has modeled the carcinogenic process in cell culture and tumor formation in immune-deficient mice. We have been investigating a type of differentiation pattern found in the basal subtype of bladder cancer which tends to be highly malignant, called squamous differentiation. We have identified gene markers and transcription factors involved in the process. Currently we are performing gene knockdowns and pharmacologic modifications to determine the molecular control of this process. Enhancing differentiation may help to slow down the progression of the cancer.
The last few years has shown that this research system is ideal for training undergraduate students (and by extension teachers) and introducing them to research in molecular biology. Dr. Somji has mentored more than 30 students over the past 10 years. Global gene expression analysis of all cell isolates yields large gene lists with common and specific gene expression patterns. This research system allows for implementation of a gene-based research experience that interdigitates well with common didactic concepts of gene regulation and as well as a chance for students to experience research-discovery in a lab setting. This also gives a basic framework to train students in basic and commonly utilized molecular biology techniques such as real-time PCR for mRNA expression analysis and westerns for protein expression analysis. Each teacher will be given three genes that have been identified as being induced or repressed from global expression analysis of the Cd+2 and As+3 isolate groups, and the teacher will perform basic informatic analysis on NCBI and background research via pub med. Each teacher will then attempt to formulate a hypothesis of why each gene may be differentially expressed based on the known function of the gene. Learning this approach to student-based research, the teacher will establish student-based research in the curriculum at their institution and perhaps even serve as a small satellite program of this research project.
Project: Mechanisms of gene expression changes in a model of metal-induced bladder cancer
Mentor: Seema Somji, Ph.D., Associate Professor; and Scott Garrett, Ph.D., Associate Professor
Location: Department pathology, School of Medicine & Health Sciences, W420
Description: This project will investigate permanent gene expression changes induced by long-term exposure to two common environmental toxicants, cadmium and arsenite. Current work focuses on characterizing the gene expression changes and transcriptional control mechanisms manifesting these permanent gene expression changes. Specific effort has focused on investigating the mechanisms of permanent induced expression for enolase-2, metallothionein-3, keratin 6A, and metallothionein 1X, N-cadherin and elongation factor 1A2. Research thus far as implicated the role of specific transcription factors and histone modifications. Understanding how permanent gene expression changes occur due to long-term environmental exposure will help understand molecular mechanisms of cellular adaptation.