"I firmly believe that our discovery will make a difference, contribute to new knowledge regarding the causes or cure of brain tumors, and bring science closer to the day when brain diseases can be accurately diagnosed and treated. The support from The Sontag Foundation will make it possible to accomplish these goals."
- Dr. Keqiang Ye
- Professor, Department of Pathology & Laboratory Medicine, Emory University School of Medicine
About DSA-Funded Research
PIKE-A, a novel GTPase that mediates human brain cancer invasion through regulating AKT
Amplification of oncogenes has been observed in tumor cell lines and primary tumor tissues suggesting that overexpression of these genes provides tumor cells with a selective growth advantage. The chromosomal 12q13-15 region is frequently amplified in about 15% of gliomas. Previously, we have identified a brain-specific GTPase PIKE, which enhances PI 3-kinase activity. Recently, we demonstrated that an alternatively splicing isoform of PIKE, designated PIKE-A, is located in 12q13-15 and amplified in human brain tumors and sarcomas. However, the pathophysiological role of overexpressed PIKE-A in glioma progression remains unknown. PI 3-kinase/Akt pathway plays an essential role in tumorigenesis. Activation of this pathway regulates essential cellular functions that underlie the biology of human cancer. Akt activation also contributes to tumorigenesis and tumor metastasis, and resistance to chemotherapy. Modulating Akt activity is now a commonly observed endpoint of chemotherapy administration. Our preliminary study demonstrates that PIKE-A binds Akt and stimulates its kinase activity and regulates glioblastoma cell invasion. To determine the role of PIKE-A in gliomas, we propose: a) To characterize the interaction between PIKE-A and Akt, and its effect on Akt activity; b) To determine the role of patient-derived PIKE-A mutation in glioma cell invasion and tumorigenesis in mice. To define the role of PIKE-A in Akt activation will lead to a better understanding of the cellular functions of PIKE-A in tumorigenesis and tumor progression, and provide the basis for identification of novel drug targets for the treatment of brain tumor patients.
"Keqiang is remarkable in a number of ways. More than virtually any other young scientist I know, he can cut through a morass of convoluted scientific detail to appreciate the essence of a problem and devise elegant, simple means of finding answers. He is an incredibly gifted experimentalist, making seemingly impossible techniques work with artistic fluidity?. I strongly suspect that Keqiang will emerge as one of our country's handful of leaders in this area."
Solomon H. Snyder, M.D.
Johns Hopkins University, Baltimore
"Certainly, Keqiang is very smart, hard working, knowledgeable, and committed to a life in science?.In summary, Keqiang Ye is a very talented, dynamic young scientist who has accomplished an impressive amount of high quality and important work in a short time."
Guy M.. Benian, M.D.
Emory University, Atlanta