Dr. Guangwei Du’s laboratory has recently received two grants for their research on vascular remodeling and cancer metabolism.
The first grant is a Research Project Grant (R01) from the National Heart, Lung, and Blood Institute to study the role of phospholipase D2 (PLD2)-regulated vascular smooth muscle cell migration in injury-induced vascular remodeling. Injury-induced vascular remodeling is directly involved in several vascular diseases, such as atherosclerosis and post-angioplasty restenosis. The successful funding of this study was based on the strong preliminary data generated by Drs. Ziqing Wang and Feng Zhang, two postdoctoral fellows in the Du laboratory, who found that inhibition of PLD2 impeded vascular smooth muscle cell migration in vitro as well as neointima formation in injured arteries using a carotid artery ligation mouse model. In the next four years, Ziqing, and Drs. Xiao Liang and Ming Cai, two visiting scientists from China, will study the mechanisms through which PLD2 regulates vascular smooth cell migration and pathological vascular remodeling, and evaluate whether inhibition of PLD2 using small molecule inhibitors can block these processes, using a combination of techniques in biochemistry, molecular cell biology, and mouse models. These studies will identify novel molecular and cellular mechanisms that underlie vascular smooth muscle cell migration, and thus, may lead to the development of new therapeutic treatments for vascular diseases. Dr. Du and his team believe that pharmacological intervention of the PLD2 pathway may represent an efficient non-toxic therapy for vascular diseases, because removal of PLD2 in mice did not cause any adverse effect.
The second grant focuses on altered lipid metabolism in cancer cells, and is funded by the Cancer Prevention Research Institute of Texas (CPRIT) CPRIT High-Impact/High-Risk Research Awards, which provide funding to explore the feasibility of high-risk projects that, if successful, will contribute major new insights into the etiology, diagnosis, treatment, or prevention of cancers. Because altered metabolism is one of the hallmarks of cancer, targeting the pathways controlling aberrant metabolism in cancer cells has been proposed as a strategy to improve current cancer therapies. Unfortunately, despite initial responses, many cancers become resistant to the current treatments and eventually relapse. Therefore, there is an urgent need to understand what makes cancer cell metabolism unique so we can design new therapies. Interestingly, two opposite activities of lipid metabolism, de novo lipid synthesis (anabolic) and fatty acid oxidation (catabolic), are both upregulated in cancer cells. An important question is how cancer cells sense their needs and respond by activating either anabolic or catabolic lipid pathways. To address this question, Maryia Lu, a graduate student, and Dr. Bangxing Hong, an instructor, will work together to investigate how the same protein, Lipin 1, controls either lipid synthesis or fatty acid oxidation, depending on the metabolic needs in cancer cells. Furthermore, they will test a new concept: the production of a lipid precursor by Lipin 1 not only controls the level of lipids, but also the synthesis of other macromolecules, such as proteins and nucleic acids. Knowledge gained from this study will help us to better understand the dependence of cancers on their altered metabolic requirements and to design new therapeutic strategies.
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