Affiliation(s):

• Associate Professsor, Department of Biological Science
• Scientific Member, Molecular Therapeutics, Karmanos Cancer Institute
• Associate Professor, Department of Oncology, School of Medicine, Wayne State University

I received my BSc in Biology from the University of Toledo, Ohio. While an undergraduate student, I spent a year studying abroad at Salford University, Salford, England. I also did a Department of Energy supported internship for one semester at the Lawrence Berkeley National Laboratory in Berkeley, California. I received my PhD in Molecular Genetics, Biochemistry and Microbiology from the University of Cincinnati Medical School, Ohio.

Coordinate spatial and temporal regulation of gene expression is essential for normal development. If genes are not expressed correctly, the function of a cell will be altered. This may result in excess cell division leading to cancerous tumors, no cell growth resulting in cell loss, or premature differentiation resulting in non-functioning cells. Misregulation of gene expression is a major cause of human disease including cancer and neurodegenerative disorders.

Gene expression is regulated in part by the interactions of DNA with genome packaging proteins, a level of regulation termed epigenetic control. Research in the Pile laboratory is directed toward understanding how genome packaging affects gene expression. We are taking a multi-pronged approach to address these questions in the model organism Drosophila melanogaster and human cancer samples. We utilize a combination of biochemical, molecular and genetic techniques to understand the mechanisms of action of gene regulatory enzymes. Data from these studies will help us understand the contributions of chromatin packaging and gene regulation to cellular decisions critical for proliferation, development and viability. 

I have been studying questions of genome regulation since my time as intern while an undergraduate student. I found it fascinating then, and still do, to consider the ways in which cells of multi-cellular organisms are programmed to do their specific jobs. All cells contain essentially the same genetic information, and yet only a subset of that information is used in any given cell type or time during development to allow the cell to perform its specific function. While in my final year of graduate school, a class of enzymes that control how DNA is packaged in the nucleus were identified by multiple laboratories. And it soon became clear that chromosomal packaging is not just inert and structural, but rather, has a large impact on whether or not a given gene is active. At that time, I decided that these enzymes were the proteins that I wanted to study. I was interested in these enzymes in large part because they don’t regulate a single gene, but instead modulate expression of hundreds of gene, which can allow a coordinated cellular response to a variety of signals. I choose to work in the model organism Drosophila melanogaster (fruit flies) because of the wealth of genetic information available and because this model is readily accessible to work by undergraduate student researchers. We are now also working with cancer cell lines as we have learned that the enzymes that we study control cell division and may be targets for new therapeutics for different cancer types

Epigenetic regulation is key to cellular gene expression. Control of the epigenome can now be impacted by a variety of drugs, which when provided, can affect gene expression to ultimately reprogram cellular activity. I am interested to work in this area of cellular reprogramming as a potential way to influence disease states through therapeutic drug treatments.

I really enjoyed The Genome War by James Shreve. The human genome sequencing project was an initiative to determine the entire sequence of the human genome, which was expected to majorly advance our understanding of human biology and disease. The book describes the “race” to sequence the human genome in the 1990’s. Two major efforts, one commercial by the company Celera Genomics, and one government funded, were being made to decipher the sequence, each utilizing different approaches to reach the ultimate goal. The author “embedded” in the commercial effort and provides insight not only into the science, but also the personalities, involved. The story highlights the fact that science advancement does not take place by a lone investigator working in an “ivory tower” but rather more often advancement is the result of collaborative and competing efforts by real people with their own biases and vision, taking place in the background of public and private investment, both social and monetary