Biological Sciences

Our current research is focused on the role of two hormones - prolactin and estrogen - in the regulation of human breast cancer. We want to know which signaling pathways link these two hormones to tyrosine kinase JAK2 and serine-threonine kinase PAK1 and to breast cancer metastasis. Our studies may identify specific biomarkers that could make it easier to detect cancer cells with metastatic potential at an earlier stage or help doctors to know that they need to look at these particular molecules during clinical evaluations.

We are interested in the regulation of PAK1 protein by JAK2 kinase. JAK2 is a tyrosine kinase that is activated by approximately two-third of the cytokine superfamily of receptors. For many of these receptors, activation of JAK2 is the initiating step in ligand-dependent signaling. Serine-threonine kinase PAK1 has been implicated in a wide range of biological functions including apoptosis and malignant transformation, cell morphology and motility, and the stress response. Although both proteins – JAK2 and PAK1 –have been implicated in the regulation of cell pathways that can lead to breast cancer but how they work together and the precise mechanism of their action is unknown. Our long term goal is to understand the molecular mechanisms that control cell division and cell motility and disregulation of which leads to human breast cancer. Toward this aim, we have started to analyze the relationship between JAK2 and PAK1. We showed that JAK2 binds to PAK1 and makes PAK1 more active. Activated PAK1 contributes to better cell survival that may promote cancer development. Our lab studies how JAK2 and PAK1 increase cell proliferation, cell motility that leads to metastasis and/or ability of cells where PAK1 protein is hyperactivated by JAK2 protein, to produce breast tumors in animals. In understanding of how these proteins work together will help to design new therapeutic approaches and possibly drugs for treatment of human breast cancer.

We are also excited by our findings that activated JAK2 plays a role on centrosomes (Jay et. al., 2015). It has been shown that a V617F gain-of-function point mutation of JAK2 is the cause of ~90% of all polycythemia vera cases and ~50% of all essential thrombocythemia and primitive myelofibrosis cases. Despite of multiple reports describing the contribution of JAK2 V617F to different pathologies, a comprehensive mechanism has remained elusive. We plan to establish collaboration with hematologic oncologists who will provide us samples, assistance and discussion of potential clinical relevance of the centrosome-located activated JAK2 in chronic myeloproliferative disorders, especially polycythemia vera.