Welcome to the lab of
The primary interest in our lab is the role of microRNAs in breast cancer progression and metastasis. Breast cancer is the most frequently diagnosed malignancy and the second leading cause of cancer deaths in American women, second only to lung cancer. This year, an estimated 178,480 new cases of invasive breast cancer will be diagnosed among women, as well as an estimated 62,030 additional cases of in situ breast cancer in the US, resulting in approximately 40,460 deaths. In fact, every 68 seconds a woman dies of breast cancer worldwide. Breast cancer mortality is almost invariably attributable to metastasis that is clinically untreatable despite aggressive chemical and radiation therapies. Additional studies directed towards elucidation of the factors involved in progression should facilitate the design of molecularly based diagnostic and therapeutic approaches. The 5 year survival rate of localized disease is 98%, however this percentage drops dramatically to 26% in patients with metastatic disease. Therefore, understanding the pathways and processes that are involved in metastatic progression is of the utmost importance to prolong survival in breast cancer patients.
MicroRNAs (miRNAs) are endogenous 19-25 nucleotide RNAs that have emerged as a novel class of small, evolutionarily conserved gene regulatory molecules involved in many critical developmental and cellular functions. miRNAs base-pair with target mRNA sequences primarily in their 3’ untranslated region (3’UTR). Through specific base pairing, miRNAs induce mRNA degradation, translational repression, or both depending upon the complementarity of the miRNA to its mRNA target. Each miRNA can target numerous mRNAs, often in combination with other miRNAs, therefore controlling complex regulatory networks. It is estimated that there are ~1000 miRNAs in mammalian cells, and that about 30% of all genes are regulated by miRNAs. Over 3,000 identified mature miRNAs exist in species ranging from plants to humans, suggesting that miRNAs are ancient players in gene regulation. Their existence and conservation throughout species supports the concept that they perform critical functions in gene regulation. Indeed, the conserved evolution of both miRNAs and transcription factors highlights their importance in and the complexity of gene regulation. What makes miRNAs particularly important is their involvement in most, if not all, fundamental biological processes. Mounting evidence indicates that miRNAs may also play a significant role in cellular transformation and carcinogenesis acting either as oncogenes or tumor suppressors.
Unfortunately, there are not many successful treatments in the clinic for women who present with metastatic disease. In addition, the 5 year survival rate for these women is very low. The significance of our work is its potential to contribute important new understanding to the genetic basis of multi-step tumor development and disease progression. The presence of specific miRNA expression may also provide another much-needed indicator of metastasis. Data collected by the SEER (Surveillance, Epidemiology, and End Result) program of the US National Cancer Institute (NCI) showed that less than 10% of breast cancer patients had detectable distant metastases at diagnosis. These facts argue that interruption of the metastatic process could be useful for a majority of individuals with breast cancer. The ultimate long-term goal of our lab is to identify novel targets of miR-204/510 that may be therapeutically targeted in breast cancer patients with invasive and/or metastatic disease with the objective to prolong survival and/or inhibit metastatic progression.
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