SUMMARY
The research laboratory of Thomas C. Spelsberg, Ph.D., is engaged in studies regarding the mechanism of action of estrogens, selective estrogen receptor modulators (SERMs), select growth factors, and transcription factors in human and animal bone and breast cancer.
In one project, he and his colleagues have shown that a transcription factor called TIEG, which was discovered in Dr. Spelsberg's laboratory, plays a major role in skeletal physiology. Its absence creates osteoporosis-like bone loss in female mice. It inhibits sclerostin, a negative regulator of Wnt signaling critical for bone formation, and is also crucial for the important actions of estrogens and transforming growth factor beta (TGF-beta)/bone morphogenetic protein 2 (BMP-2) on bone. It has recently been identified as one of several genes — out of hundreds — whose expression is consistently altered in human osteoporosis.
In another project, Dr. Spelsberg's lab helped identify endoxifen, the tamoxifen metabolite, as the primary inhibitor of breast cancer growth. His lab has shown that endoxifen is more potent in its action when estrogen receptor beta (ER-beta) is expressed in breast cancer cells. Using new anti-ER-beta antibodies developed by his laboratory, Dr. Spelsberg and his colleagues have more accurately identified the ER-beta receptor isoform in many human breast cancers that have been previously designated as estrogen receptor alpha (ER-alpha) negative. This opens the door for the preferred hormone (tamoxifen/endoxifen) therapy for many women in place of the more radical chemotherapy.
Focus areas
- Examining the critical mechanisms by which the transcription factor TIEG enhances the Wnt signaling pathway in the skeleton and serves as the point of crosstalk between estrogen and TGF-beta/BMP-2 in bone
- Determining the expression of ER-beta in human breast cancers 1) as a predictor of breast cancer responses to endoxifen/tamoxifen therapy, 2) for correlation with patient outcome, and 3) selecting the previously designated ER-negative patients for hormone (SERM) therapy
Significance to patient care
The long-range goals of Dr. Spelsberg and his team are to:
- Use TIEG expression as a marker for osteoporosis and other bone diseases
- Use agents/drugs that enhance TIEG expression to reverse bone loss in humans
- Better identify human breast cancer patients whose tumors express the ER-beta isoform for predicting 1) patient response to SERM (TAM) therapy, and 2) which patients would respond best to tamoxifen
- Identify those ER-alpha-negative cancer patients who express ER-beta for hormone therapy instead of chemotherapy
Professional highlights
- Board of Directors, George M. Eisenberg Foundation (funding charities and medical research), 1990-2012
- External Advisory Board, West Virginia University Health Sciences Center, 2001-2012
- Governing Council, American Society for Bone and Mineral Research, 2004-2007