The overall goal of the work in my lab is to use yeast to study problems in cell biology and cancer. Previous work has focused on the use of genetics to understand cytoskeletal structure and function. More recently, we have started using yeast to understand how environmental exposure and genetic factors influence the risk of genomic instability in cancer. During cancer development, chromosomes undergo breakages that lead to rearrangements, which are often unstable and consequently result in further breakage and rearrangements. Such events lead to translocations, deletions, inversions etc, and may result in altered gene products and/or changes in gene expression. This, in turn, can affect growth control, and consequently lead to cancer. My lab is using yeast as a model organism to study genomic instability. In particular, this entails (i) using the extremely powerful genetics possible with this yeast system to identify genes that are normally required to stabilize the genome; (ii) determining whether uranium and arsenic, found in well-water on the Navajo Reservation, increase genomic instability in yeast; (iii) extending these observations to human cells by determining whether human orthologs of genes identified in yeast cause DNA rearrangements in human cells t

This faculty member is also a mentor in the NSF IGERT graduate training program: NAU’s IGERT PhD program seeks to identify key links between genes and the environment and is designed to train exceptional graduate students in molecular genetics, environmental sciences, and spatio-temporal modeling.hat are relevant to cancer.

Using yeast to understand the role of environmental contaminants in genomic instability and cancer: This work is funded by the Native American Cancer Research Partnership (NACRP), which is a collaboration between NAU, The University of Arizona, and the Native American community. On the Navajo reservation, there is an elevated incidence of various cancers, and it has been suggested that this is caused by abnormally high levels of uranium and arsenic present in mine-tailings and well water. One of the features of cancer cells is that chromosomes undergo frequent breakages that lead to rearrangements, causing mutations and alterations in gene expression. Environmental factors are known to cause DNA breakage, leading to the question of whether arsenic and uranium lead to increased levels of genomic instability. We are addressing this question using yeast (Kandl et al. 2002), which has tremendous advantages as an experimental organism (e.g., Munshi et al. 2001; Whitacre et al. 2001; Adams et al. 1997). In particular, we are examining the effect of uranium and arsenic on genomic instability in yeast. Because of the great similarities between underlying cellular processes in yeast and humans, it is likely that our studies in yeast will be directly applicable to similar studies of human cells. Combined with investigations regarding the uranium and arsenic contamination, effects and remediation on the reservation by Drs. Loretta Mayer, Cheryl Dyer, Jani Ingram, and Diane Stearns (NAU), this study provides pivotal linkages between environmental issues and human health.