Speaker Bio
Dr. Stephen Hammes’ research interests include steroidogenesis and steroid signaling, with a focus on extranuclear, or nongenomic, steroid effects. He studies these processes in the context of female reproduction, where his lab has demonstrated the importance of androgen signaling in normal ovarian function. In addition, the Hammes lab studies steroid hormone signaling in hormone-sensitive cancers such as prostate cancer and lymphangioleiomyomatosis (LAM).
"Lymphangioleiomyomatosis (LAM): The “Other” Hormone-Sensitive Cancer"
LAM is a rare cystic lung disease found almost exclusively in women. The cystic lung changes are caused by small multifocal smooth muscle cell clusters in the lungs that contain mutations in one of the two tuberous sclerosis (TSC) genes. In patients, LAM is highly estrogen sensitive, as it worsens with puberty, pregnancy, and oral contraception, and stabilizes after menopause. To explain the remarkable female predominance of LAM and its estrogen sensitivity, we proposed that LAM smooth muscle cells in the lungs may originate from the myometrium of the uterus. In fact, when we knocked out TSC2 expression in the uterus, all mice developed aggressive myometrial growth that resembled LAM, with 50% developing lung myometrial nodules from the uterus later in life. Mouse TSC2-null uteri were highly sensitive to estradiol, as growth was eliminated with oophorectomy or aromatase inhibitor treatment.
In contrast, isolated LAM cells from these mouse uteri and other TSC2-null cells had minor estradiol sensitivity in vitro, suggesting that in vivo estradiol promotes LAM progression indirectly. Using various strategies, we have discovered that, in addition to directly stimulating LAM cells, estradiol enhances innate immune responses that promote LAM progression. We have also begun elucidating estradiol-related pathways that modulate innate immunity in the bone marrow and tumor bed.