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June 3, 2014

Dan Hollern: Making a difference in cancer research

June 4, 2014

Dan Hollern is a graduate student in the College of Natural Science studying cell and molecular biology.

As a graduate student working towards my Ph.D., my ultimate goal is to make a difference in human health with meaningful and translational cancer research. At Michigan State, I have had the unique privilege to utilize cutting edge technology in my research.

Under mentorship from Eran Andrechek, assistant professor of physiology in the College of Human Medicine, I have benefited from a highly integrative and wide-ranging training environment. Amongst the variety of tools that I have mastered during my soon-to-be-completed dissertation, perhaps the most useful skill I have learned is the use of microarray technology to study the gene expression features of breast cancer.

Microarray technology allows the expression of more than 14,000 genes in a tumor sample to be surveyed. By expanding the analysis to a large number of samples and by applying sophisticated mathematical methods, information about many genes that may cause differences in cancer progression can be uncovered. This computational approach is one of the factors that enable me to pose questions for my research.

My research is focused on addressing the many differences between breast cancer samples from different patients. These differences make it impossible to treat all tumors with the same drugs. To date, some success in understanding these differences have been achieved, with breast cancers being organized into different subtypes on the basis of key genes. Personalized therapies for specific types of breast cancer have improved survival, yet treatment is still inadequate with tumors developing resistance to therapy.

To simplify the study of breast cancer, researchers have taken advantage of numerous preclinical models. However, how well these models mimic human breast cancer had yet to be demonstrated. To do this, I designed a project that uses the power of large scale gene expression data. Specifically, I generated and analyzed a database of gene expression data from over 1000 samples from preclinical models and over 1000 human breast cancer tumors.

With this expansive database, I analyzed the gene expression data through a variety of mechanisms to ask how models are distinct, what properties they share and how they reflect human breast cancer. This work was recently published in Breast Cancer Research.

With the completion of this work, I am now moving to research where I use a cross-disciplinary approach to study the process of how breast cancer cells spread to distant organs of the body. The reason this is important is that the spreading of tumor cells (or the metastasis) to distant organs is what makes cancer lethal.

The changes that allow for cancer cells to detach from the tumor, enter the blood stream, and establish new tumors in distant organs are incredibly complex. As a result, the genes that cause cancer cells to spread are largely unknown.

To predict genes that may cause cancer cells to spread to distant organs, I again used large-scale genomic experiments. With a large database of breast cancer patient data, I tested which genes were active in patients with metastatic tumors.

This led to the identification of a gene known as E2F1 as being involved in the spread of cancer to other organs. In my experiments I found that this gene allowed cancer cells to invade blood vessels and allowed tumors to grow in distant organs such as the lungs.

Importantly, by comparing genes that changed when we removed E2F1, I found how E2F1 controls tumor cell spreading. For example, I found that E2F1 controls blood vessel recruitment to the tumor, which allows tumor cells to get into to the blood stream.

Importantly, as part of the Spartan community’s emphasis on expanding cancer research at MSU, my continuation of this research project was sponsored with a fellowship from the Aitch Foundation and the MSU Health Team.

In addition to these research accomplishments, the unique training I have received while in Dr. Andrechek’s lab has also provided experiences that will be sure to enhance my professional development. I have been able to publish in well-respected journals, present my work at national conferences, network with other scientists and collaborate with a wide variety of labs both here at Michigan State and throughout the country.

As I near completion of my dissertation, I know that these experiences have prepared me for the next step of my career as cancer researcher. The investment in my training by Dr. Andrechek, MSU, and the Aitch foundation will echo in the new research goals I will pursue as a post-doctoral researcher. It has been truly a blessing to pursue my graduate degree with meaningful and translational cancer research made possible by their support.