deGraffenried, Linda Ann

• Associate Professor
• PhD, UT Health Science Center at San Antonio, 2001
• NTR
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• Office: PAI 4.36C
• Office Number: 512-232-9410
• Fax: 512-471-4661
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• Publications

My laboratory is exploring the mechanisms by which the Akt kinase, a key mediator of growth factor signaling, confers resistance to multiple forms of cancer therapy, and why inhibition of some of its downstream targets, most notably the mTOR kinase, restores therapeutic response. This is a significant clinical problem, and as such we collaborate with clinical colleagues in translating our results into clinical trials, as well as using clinical specimens and observations to develop better in vitro (both tissue culture and animal) models for addressing the role of Akt in the etiology of resistant breast disease, and developing more effective, less toxic approaches for treating this subset of tumors. 

Additionally, since the Akt kinase also appears to play a critical role in the development of hormone-resistant prostate cancer, we are also currently investigating the mechanisms by which Akt mediates prostate cancer progression, and if inhibition of Akt signaling can abrogate this progression. We are conducting both in vitro and in vivo studies to elucidate the components of the signal transduction cascade that are critical for prostate cancer progression, and to determine at what stage of the disease Akt activity is essential. In addition, we are again using compounds that are currently in clinical development to assess their efficacy at preventing hormone-resistant prostate cancer. 

My laboratory has recently expanded upon these resistance studies to develop a program that also investigates the role of the Akt signaling pathway in the development of metastatic disease. We have initiated studies examining the role of Akt in regulating cellular mechanisms, such as invasion and angiogenesis, that are necessary for breast cancer metastasis, and whether in vivo, use of Akt inhibitors currently in clinical development are effective at inhibiting metastatic progression to the bone and lungs. 
In addition to these more conventional areas of study, my laboratory has also been investigating the use of non-conventional approaches for the treatment of hormone-resistant breast and prostate cancer. Currently we are investigating whether omega-3 fatty acid modulation of processes that are linked to the Akt kinase pathway prevents prostate cancer progression to a state of hormone independence by precluding the ability of prostate cancer cells to survive during androgen deprivation and proliferate in an androgen-independent manner and how polyunsaturated fatty acids modulate androgen receptor expression.