Leszek Kotula, MD/PhD
Research Programs and Affiliations
- Biomedical Sciences Program
Cancer biology, cell signaling, the role of actin cytoskeleton in tumor progression, mouse models of cancer
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The goal of our research is to understand the molecular and cellular processes underlying human cancer. Cancer models are an important tool that we use to investigate the molecular changes, which occur as a normal cell transforms and progresses into a pre-malignant lesion, then a tumor, and finally metastatic disease. My lab developed a novel preclinical model of prostate cancer in mice by introducing a conditional knockout mutation of Abi1. The function of Abi1 is not fully understood. It appears to have a key role in growth factor receptor signaling and actin cytoskeleton remodeling. Importantly, our mouse model demonstrates that Abi1 is a tumor suppressor gene. We will use the Abi1 knockout mice to identify the molecular changes associated with the development of prostate cancer. This model will also enable us to dissect the mechanisms underlying Abi1's role in prostate cancer. These studies include the role of actin cytoskeleton dysregulation in tumor initiation and progression (i.e. the role of Abi1 in regulation of cellular adhesion and cell motility), regulation of c-Abl and PI-3 kinases by Abi1, and regulation of macropinocytosis (a type of endocytosis) by Abi1. In addition, we plan to evaluate Abi1 as a possible target for drug development in anti-cancer therapy. These studies will ultimately help us develop personalized anti-cancer therapies. Finally, recent studies indicate that knowledge from the prostate Abi1 knockout mouse model will be useful for studies of mechanisms leading to other types of cancer, such as breast, stomach, ovarian, and brain cancer, as well as leukemia.