Current Research Studies
Finding Genes for Uterine Fibroids
The aim of this study is to identify genes critical to the formation of uterine fibroids. Some women with uterine fibroids may have one or more genes that make them more likely to develop uterine fibroids. Sibling pairs who have medically or surgically documented uterine fibroids are eligible for the study.
Uterine Leiomyomata Cytogenics, Tissue Bank, and Database
The long term objective of our research is to identify, isolate, and characterize genes involved in the biology of uterine leiomyomata in an overall effort to understand genetic contributions to the etiology, growth, and natural history of these tumors.
To this end, we have established a cytogenetic database and tissue bank, and we continue to collect, karyotype, and establish cell cultures from leiomyomata and matched myometrium. In addition to karyotypes and other cytogenetic information, the database also contains the dimension, histologic diagnosis, and location of the tumors, as well as menstrual cycle stage.
This collection provides an excellent source of tissues for evaluation of different mutations within the cytogenetic subgroups of leiomyomata and for detection of novel rearrangements that will suggest the location of other genes involved in the pathogenesis and pathobiology of fibroids. The tissue database is also a valuable resource for analysis of gene expression in the context of chromosomal aberrations and for clinical studies.
Comparing Options for Management: Patient Centered Results for Uterine Fibroids (COMPARE-UF)
COMPARE-UF is a registry designed with input from women with fibroids that will gather information from women having treatment for uterine fibroids. This information will be used to help future patients, clinicians, and others make the most informed decisions about the best type of treatment for each patient's situation.
For more information about enrolling in this study at Brigham and Women's Hospital, please contact our study coordinator, Sophie Salas, at email@example.com or 617-525-9757.
Past Research Studies
Understanding the Growth of Uterine Leiomyomas
Our laboratory has been performing research studies on uterine fibroids for over ten years. These studies includes basic biology studies to help us understand what makes fibroids grow and what types of growth factors fibroids produce that may cause the abnormal uterine bleeding associated with fibroids. We are currently focusing on identifying compounds that inhibit the actions of specific growth factors that are known to be mitogenic in uterine fibroids. Some of the compounds we have identified with potential therapeutic value are anti-fibrotic agents such as pirfenidone and halofuginone, anti-angiogenic molecules such as interferons, and tyrosine kinase inhibitors. We have found that these compounds not only inhibit the proliferation of fibroid cells but also inhibit collagen production and may also cause an increase in programmed cell death. They also decrease the production of certain growth factors produced by fibroid cells.
We are now beginning to use Affymetrix cDNA microchip arrays to study changes in gene expression in fibroids on a much larger scale. The Affymetrix chips contain many thousands of genes, and we can look for changes in expression of these genes in fibroid tumors compared to normal myometrium. More importantly, we are using the microchip arrays to study changes in gene expression in fibroid cells that are treated with the compounds described above, such as interferon-beta and halofuginone, in order to gain better insight into the mechanisms of actions of these compounds. We hope to identify genes previously unknown to play a role in the growth of fibroids using these microchip arrays.
Another study underway in our laboratory is to investigate the role of a new family of growth factors in the growth of fibroids. These growth factors are all members of the connective tissue growth factor family and have been shown to play a role in tissue fibrosis. One member of this family called CCN5 appears to inhibit the proliferation and migration of fibroid smooth muscle cells. We are developing a nude mouse model to study the effects of this growth factor in vivo.
HMGA2 expression in uterine leiomyoma
Uterine leiomyomata (UL), the most common pelvic tumors in women, are the primary indication for one-third of hysterectomies performed annually in the United States. The goal of our research is to identify genes that affect the development and growth of these tumors and understand the mechanisms by which they act. One such gene is HMGA2, an architectural factor expressed during embryogenesis that is involved in differentiation and proliferation of mesenchymal tissues. We recently discovered through a TDT analysis that a single allele of a polymorphism in the 5' UTR of HMGA2 was transmitted to offspring along with "the disease" (i.e., UL) at a statistically significant rate (p = 0.0004). Thus, we are now in the exciting position of assessing the polymorphism as a functional sequence variant that may influence genetic liability to developing UL. I am examining potential correlations between the polymorphism and HMGA2 expression by obtaining UL and myometrium from women undergoing hysterectomy or myomectomy as well as conducting in vitro studies. I propose that women with a specific allele have elevated expression of HMGA2 resulting in increased proliferation of their myometrium, predisposing to UL formation. Ultimately, understanding the mechanisms of UL development, including the role played by HMGA2, could lead to innovative therapies for these tumors.