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2016 Research Grant Recipient:
Dr. John Hudson

Posted on: January 17th, 2017
Dr. John Hudson: Biological Sciences, University of Windsor
Plk4 haploinsufficiency as a genetic predisposition for hematological malignancies
SUMMARY OF RESEARCH PROJECT

The polo-like kinases (PLKs) are important proteins that are required for cells to divide normally. Abnormal levels of these proteins have been linked to the improper division of cells, a hallmark of cancer. In humans, the PLKs have been implicated in  several different types of cancer including breast, liver, skin, and colorectal. To study the effects of one of these genes at a more functional level, we have developed a mouse model that is genetically modified and only has one copy of the PLK4 gene. This mouse develops several different types of cancers such as liver and lung cancer at a much higher rate than normal mice. Recently, we noticed that this mouse, as it ages, also displays both abnormal bone marrow and an enlarged spleen. We find an irregular distribution of cells and an abnormal level of key proteins that are important for normal cell function. These proteins are known to change in level or activity in blood cancers. Thus the abnormal bone marrow and enlarged spleen, along with the other molecular features that we have detected, suggests that this mouse has developed a type of blood cancer. Our preliminary data suggests that the mouse may be a model for a myeloid and/or lymphoproliferative neoplasia. Based on our initial observations, we will be conducting experiments using several techniques to look at cell division, protein levels, and other markers of these cancers. We will also be conducting research in human patient samples to determine if the level of PLK4 protein is altered and whether this is correlated with changes  in other key markers of cancer. Through our research we hope to more accurately determine the role that the PLK4 protein as well as additional novel proteins may play in these blood cancers. Our findings will contribute towards a better
understanding of what goes wrong within cells that lead to the development of these disorders and whether PLK4 may be an important marker for early detection, an indicator of prognosis or potential targets for intervention for these cancers.

HOW THIS RESEARCH HELPS ADVANCE QUALITY CANCER CARE IN OUR COMMUNITY

Having a better understanding of the molecular mechanisms involved in cancer development can provide avenues for new therapeutic development and innovative approaches to treatment. Our research has the potential to provide new markers for earlier detection of myeloid and/or lymphoproliferative neoplasms. Additionally, we have the potential to further characterize subtypes of these general neoplasias that may help define individuals that respond better to a specific treatment regime. This may provide opportunities for generating new molecular targets that could be indicators of prognosis and the development of drugs towards treatment. One of the key areas where our research may be beneficial is in the development of a novel mouse model, which can be used to aid the researcher and clinician to develop better strategies for dealing with the human form of the disease.

Click here for a PDF version of this Seeds4Hope Research Grant Summary.

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