As a graduate student at Northwestern, Daniel Foltz, ’01 PhD, fell in love with studying cell division. Now an associate professor of Biochemistry and Molecular Genetics, he studies chromosome instability, a hallmark of cancer, and the epigenetics behind autism.
“Because of the dramatic morphological changes that occur in the cell during division, this process has been studied for over 100 years.” Foltz said. “But we are only recently starting to know the basic biochemical and molecular processes that drive chromosome segregation so that we can fully understand how this process occurs.”
What are your research interests?
My research interests focus on understanding the molecular mechanisms that ensure proper chromosome segregation during cell division. Chromosome segregation is orchestrated by the centromere, which is a unique locus present on each chromosome. The task of developing a human adult from a single cell requires trillions of cell divisions. Errors in chromosome segregation can lead to birth defects. Later in life, most cancers have too many or too few chromosomes in a cell, a state called aneuploidy. This shuffling of chromosomes (and segments of chromosomes) allows cells to acquire the unique characteristics of cancer cells that allow them to proliferate almost unchecked.
More specifically, our lab is interested in how the location of the centromere is determined on each chromosome. DNA sequence does not dictate its location, instead a poorly determined epigenetic mechanism establishes the centromere locale that relies on a centromere-specific nucleosome containing the histone H3—variant CENP-A. Centromere identity of a locus is inherited across cellular generations. Therefore, assembly of centromere chromatin is a key step to maintaining centromere identity and ensuring proper chromosome segregation. Our work has identified the proteins required for CENP-A assembly and understanding how these proteins work together to ensure the epigenetic inheritance of centromeres and thus proper segregation of chromosomes.
Also, we are studying the epigenetic underpinnings of autism. In autism there are a few recurrent gene mutations, which account for only a small subset of autisms cases. Many de novo DNA mutations in different genes have been identified that are associated with autism. If you look at the function of the genes affected by these de novo mutations, several fall into the class of epigenetic modifiers. We are working to learn the functions of some of these modifiers with the hope of understanding common epigenetic mechanisms that may be perturbed in autism.
What is the ultimate goal of your research?
Our goals are two-fold in the lab: to understand the basic mechanisms that drive chromosome segregation and epigenetic inheritance and to identify the role of chromosome mis-segregation in cancer as a causative process and potential therapeutic target.
How did you become interested in this area of research?
As a graduate student at Northwestern, I was studying Notch-Delta signaling and raised several antibodies against Notch to study its localization in the brain. Unfortunately, my antibody cross-reacted heavily with a microtubule associated protein, so the first time I looked at cells stained with the antibody, I saw these fantastic microtubule spindles in the cells undergoing mitosis. While I failed to make a good Notch antibody, I fell in love with the beauty of cell division. As I begin to delve into the literature of chromosome segregation, I realized the epigenetics of centromere specification was an exciting puzzle that I wanted to solve.
How is your research funded?
Our work on,chromosome segregation has been funded by a variety of agencies. We were supported by a Basil O’Connor award from the March of Dimes, based on the role of chromosome mis-segregation in generating birth defects. The American Cancer Society supported our work in understanding how the histone chaperone contributes to centromere identity through a research scholar grant. Recently, our work on centromere specification and posttranslational modifications of the centromere are supported by an R01 from the NIGMS. Preliminary work identifying UBR7 as a chromatin reader was supported by the National Institute of Child Health and Human Development for its potential to elaborate pathways involved in autism.
Who inspires you?
My 9-year-old son, Sam, is a great inspiration to me. We hope the experiments we do in the lab will help people live better lives in the near future, and I want to be sure that we make it better for his generation. He is also a taskmaster. When I tell him about an experiment we are in doing the lab, he wants to know the outcome, and he will ask me, for weeks, how the experiment turned out. So he keeps me motivated too!
What do you enjoy about teaching/mentoring young scientists in the lab?
The trainees are the heart and soul of the lab. I enjoy the unique perspective that each trainee brings to our research efforts. It’s those moments of synergy between lab members that gives me the most satisfaction – when you know the discussions and interactions in the lab fostered an insightful new idea or realization, as well as sharing those “aha” moments with the trainees that come from hard work and deep thought.