Gerald M. Adair, Ph.D.
1975, Washington University, St. Louis
The University of Texas M. D. Anderson Cancer Center
Department of Carcinogenesis
My laboratory is located in Smithville,
Texas, at UT Science Park -- Research Division.
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Gerald M. Adair, Ph.D. 1975, Washington University, St. Louis The University of Texas M. D. Anderson Cancer Center My laboratory is located in Smithville,
Texas, at UT Science Park -- Research Division. |
Research Interests:
1) About 70% of all breast cancers are dependent on the female hormone estrogen for growth. Patients are usually treated with surgery and given anti-estrogens as an adjuvant therapy. The anti-estrogen Tamoxifen has been the gold standard for endrocrine treatment of all stages of hormone responsive breast cancer for more than 25 years. Many of the tumors that initially respond to Tamoxifen therapy with time develop resistance. Almost all recurrent breast tumors ultimately become resistant to anti-estrogen treatment.
The molecular mechanisms for the development of anti-estrogen resistance are still poorly understood. This is precisely one of the major topics of research in my laboratory. We have discovered that a protein called CtIP is critically involved in the development of Tamoxifen resistance. This protein interacts with multiple partner proteins that in turn are very important in breast cancer, such as the breast cancer suppressor protein Brca1 and repressors of gene transcription such as CtBP. We hypothesize and have accumulated abundant evidence indicating that the loss of CtIP is a critical event in the development of resistance to therapy by the anti-estrogen Tamoxifen. We are currently conducting further studies to better understand the mechanistic implications of our observations.
2) A few years ago we were the first laboratory to discover and clone a gene mapping to a region of chromosomal fragility in human chromosome 16. This common chromosomal fragile site region is called FRA16D. It is the second most common site of the human genome prone to breakage, rearrangements and the occurrence of abnormalities. This site is also frequently affected by losses of genetic material in a myriad of cancer such as breast, prostate, liver, ovarian cancers among other solid tumors. Chromosomal translocations affecting this site and the gene we discovered are also found in multiple myeloma, a hematological malignancy. We name this gene WWOX, because it is characterized by the presence of protein-protein interaction domains called WW domains and it is an enzyme, more precisely and oxidoreductase, likely to be involved in the metabolism of steroids. We and others have published abundant evidence demonstrating that WWOX behaves as a tumor suppressor/susceptibility gene since its activity is missing or reduced in multiple cancers. We have now genetically engineered mice lacking targeting this gene for loss. These mice are also predisposed to the development of certain cancers. We are currently characterizing these animals. We are also attempting to better understand the physiological role of WWOX in normal cells and the effects of its lost in cancer cells.
3) As a result of global gene expression breast cancer studies, we have generated unique data sets on the expression of genes in breast cancer. We are currently mining this extremely valuable data sets for the identification of genes that can be of used as biomarkers of relevance in diagnosis/prognosis of breast cancer. We have published numerous studies on this topic.
4) Similar studies to those described in 3 have been performed with multiple mouse models of mammary cancer. We have generated abundant evidence validating the use of specific mouse mammary cancer models in which multiple aspects of the human counterpart cancer are reproduced. We identified multiple genes that are identically affected both in mouse and human breast cancer. These observations allow us to use the aforementioned mouse models as subrogates for the testing of novel chemopreventive therapies. We are conducting studies on the chemoprevention of mouse mammary cancer in collaboration with other laboratories at Baylor College of Medicine.
Program Affiliation: