HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY M
The award will focus on a common but poorly understood disease of the human female reproductive tract, uterine leiomyomas. Our preliminary findings deomonstrate that leiomyomas alter their molecular expression patterns to decrease retinoic acid concentrations. In order to determine why this occurs, we have developed multiple immortalized human leiomyoma and myometrial cell lines to assess the impact of retinoic acid on both the molecular and structural phenotype on human leiomyoma cells and patient-matched myometrial cells. It is critically important to identify and elucidate novel mechanisms controlling liomyomas development. These tumors not only cause significant symptoms for the women burdened with them, but they also can disrupt otherwise healthy pregnancies. Current therapies highlight our limited understanding, as they are directed at either depriving the tumors of their nutrient source, or temporarily shrinking the tumors with hormonal manipulation. The involvement of the retinoic acid pathway provides a potentially novel therapeutic approach once the mechansim is more clearly understood. We propose to clarify the role of retinoic acid by performing functional studies.