I was born in Thailand but grew up in Lawrence, Kansas.I attended the University of Kansas for my undergraduate training. Working as a research assistant in a cancer biology laboratory after my BS degree continued my interest in science and research, and after a year I applied for admission to physician scientist programs.
My current area of research interestinvolves estrogen and its roll in mammary carcinogenesis.
Sporadic breast cancer accounts for 85-90% of all breast cancer cases and it is evident that both endogenous and exogenous estrogens are risk factors.Although estrogen is widely accepted as a tumor promoter, little is known about the role of estrogen as a tumor initiator.Our previous studies have shown significant aneuploidy (abnormal chromosome number) or genomic instability in estrogen-induced tumors but this finding was not unexpected because the vast majority of solid tumors have karyotypic abnormalities.Although in 1929 Theodore Boveri proposed the hypothesis that genomic instability was a cause of tumorigenesis, the prevailing theory has been that genomic instability is a result of cancer and thus less important for understanding the mechanism by which tumors arise. However, our lab, as well as several others, have recently shown that pre-malignant (not yet "bad" invasive tumors) lesions called ductal carcinoma in situ (DCIS) are also highly aneuploid, suggesting an early (i.e. causative) rather than late (i.e. promotion of "already-formed" tumors) role for estrogen in mammary carcinogensis.
The mechanisms by which estrogens cause genomic instability are still unclear.However, in vitro studies have shown a link between the overexpression of cyclins (proteins that regulate cell-cycle progression) and genomic instability. More recent data suggests the involvement of centrosome amplification (too many centrosomes) in the induction of genomic instability and subsequent aneuploidy.Cyclin overexpression and centrosome amplification have both been demonstrated in ACI rat mammary DCIS as well as human breast cancers.
Our model is unique because only near-physiologic serum levels of estradiol are required to induce mammary tumors in the ACI rat at 100% incidence while no spontaneous tumors are observed in untreated controls.Because cyclins have been shown to cause genomic instability in vitro, my research focuses on the characterization of cell cycle regulatory proteins like cyclin D1, D2, D3, and E1 at the protein, RNA, and DNA level in pre-neoplastic (not yet "tumor") lesions and mammary tumors.Pre-neoplastic lesions will be analyzed to determine which genetic changes are most consistent.
©
The University of Kansas Medical Center