Associate Professor
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Mail Code: A1915, PHR Room 5.224A |
Office phone (512) 471-5199
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Laboratory Interests
Several studies have shown that IGF-I (Insulin-like Growth Factor-I)
conveys pro-tumorigenic responses in breast, colon and prostate cancer.
Our research focus is in understanding how IGF-I inhibits cell death in
breast cancer. IGF-I often interferes with the ability of anti-cancer
agents to induce cell death. To better understand its function, we study
growth factor and stress mediated cross-talk in breast cancer models.
IGF-I exposure of breast cancer cells activates its membrane bound receptor
(IGF-IR) which then induces the activity of various kinases. The activation
of many kinases by IGF-I exposure requires the binding of IRS-1 (Insulin
Receptor Substrate-1) to IGF-IR. IRS-1 then binds to phosphatidylinositol
3-kinase (PI3K) (amongst other proteins) to induce the PI3K mediated pathway,
an essential event for IGF-I survival responses in breast cancer. We have
recently focused on IRS-1 since its activity increases in response to
IGF-I through tyrosine phosphorylation. In contrast, stress treatments
down regulate cellular sensitivity to IGF-I via IRS-1 serine or threonine
phosphorylation. Our research and others' have recently shown that two
PI3K sensitive proteins are integral to both IGF-I and stress mediated
effects in breast cancer. They are mTOR (mammalian target of rapamycin)
and JNK (c-Jun N-terminal Kinase). mTOR and JNK activity increase in response
to IRS-1 activation. mTOR and JNK then down regulate IRS-1 activity in
different fashions. We are currently studying how mTOR influences IGF-I
mediated survival through the retinoblastoma tumor suppressor protein.
Our long-term goal is to better understand how to use agents that inhibit
growth factor mediated responses to improve breast cancer treatment.
My lab has had a long-standing interest in various functions of JNK in
breast cancer models, a kinase traditionally characterized as pro-apoptotic
and necessary for many anti-cancer agents to induce cell death. Recent
studies have demonstrated that JNK is also activated by growth factors
to increase cell migration and survival, properties essential for cancer
cells to move to distant sites and metastasize. There are three different
jnk genes. The resulting JNK proteins were all initially thought to function
similarly. However, most studies thus far have shown that jnk1 and jnk2
gene products convey diverse functions in various diseases such as diabetes,
leukemia and skin cancer research. To better understand the specific functions
of JNK proteins in breast cancer we are studying the role of jnk1 and
jnk2 loss in mammary gland development, mammary tumorigenesis/metastases,
and response to chemotherapy treatment. Thus far, we have shown that loss
of JNK expression inhibits mammary tumorigenesis and metastatic burden
using mouse models. Ultimately we hope to evaluate if JNK can be therapeutically
targeted to treat breast cancer patients.
| November 6, 2008 Faculty Directory College of Pharmacy at UT Austin Comments to: pharmacy@www.utexas.edu |
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