Luke H. Hoeppner, Ph.D.
Assistant Professor
Molecular Biology and Translational Cancer Research
507-437-9623
lhoeppner@hi.umn.edu

Our molecular biology and translational cancer research is funded by the National Institute of Health to study the molecular mechanisms and signal transduction pathways involved in vascular permeability, lung cancer progression/metastasis, and cancer drug resistance.

One goal of our work is to develop new therapies to inhibit lung cancer progression and prevent tumor cells from acquiring resistance to current treatments. We accomplish these goals through the use of a variety of models as well as utilization of lung cancer patient samples. Our research aims to improve the dismal survival rate of lung cancer patients and seeks an innovative approach to combatting tumor drug resistance. This research will have collective impact because its studies will identify novel therapeutic targets to help the multitude of Americans suffering from lung cancer. For example, we recently showed molecules that bind to dopamine D2 receptor inhibit lung cancer progression by reducing tumor angiogenesis, the process through which a tumor obtains its necessary blood supply to survive and grow. Currently, we are investigating other molecular components of the dopamine signaling pathway that have been implicated in breast drug resistance and thus may play a role in acquired resistance to commonly used lung cancer treatment regimens.

Another aspect of our research focuses on vascular permeability, or veins becoming “leaky”. We study a molecule called vascular endothelial growth factor (VEGF), which promotes formation of veins.  High expression of VEGF causes leakiness in the veins.  Following a heart attack or stroke, VEGF is highly expressed leading to leaky veins and tissue damage.  Identification of genes and mechanisms that regulate leakiness caused by VEGF will help develop new therapies to promote recovery from heart attack and stroke. Furthermore, VEGF-induced vascular permeability contributes to cancer growth and metastasis.  Genes have been identified that regulate the leakiness in veins caused by VEGF.  We are studying the mechanisms one of these genes, a receptor that binds VEGF, uses to regulate leakiness of veins.  To answer this question, we are using transgenic zebrafish that enable us to turn VEGF “on” and the receptor “off”.  We are also developing a high-throughput zebrafish model that will allow us to conduct screening experiments to identify new genes that regulate leakiness in veins caused by VEGF. After heart attack or stroke, VEGF plays a beneficial role by promoting tissue repair, but also causes veins to leak resulting in additional tissue damage.  Given the complex role of VEGF in these diseases, it is important to identify the precise mechanism by which VEGF regulates leakiness of veins.  Understanding the process will enable researchers to develop new drugs that will help patients recover from cancer, heart disease, and stroke.