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C. Marcelo Aldaz, M.D., Ph.D.

Present Title & Affiliation

Primary Appointment

Professor, Department of Carcinogenesis, Science Park-Research Division, The University of Texas M.D. Anderson Cancer Center, Smithville, TX

Dual/Joint/Adjunct Appointment

Professor, University of Texas Health Science Center, Houston, TX

Research Interests

Research Interests:  Breast cancer genetics, carcinogenesis, mammary tumor models, breast cancer biomarkers, tamoxifen resistance

Two areas of research interest include:
1) We are the first laboratory to discover and clone the tumor suppressor gene WWOX. This gene maps to a region of chromosomal fragility in human chromosome 16. This locus is frequently affected by losses of genetic material in a myriad of cancer such as breast, prostate, liver, ovarian cancers among other solid tumors. WWOX, is characterized by the presence of protein-protein interaction domains called WW domains and an oxidoreductase enzymatic domain, 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 conditional KO mice to study the effects of WWOX ablation in normal cells and the role of this protein in oncogenesis. We are also studying the role of WWOX in the development of breast and prostate bone metastases.

2) About 70% of all breast cancers are dependent on estrogens for growth. The anti-estrogen Tamoxifen has been the gold standard for endrocrine treatment of all stages of hormone responsive breast cancer. 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. We have recently discovered that a protein called CtIP is critically involved in the development of Tamoxifen resistance. CtIP interacts with the breast cancer suppressor protein BRCA1 and the transcriptional repressor 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 and CtIP is a key co-repressor of the estrogen receptor. We are currently conducting further studies to better understand the mechanistic implications of our observations.


Education & Training

Degree-Granting Education

1983 University of Buenos Aires Medical School, Buenos Aires, Argentina, PHD, Experimental Pathology
1980 University of Buenos Aires Medical School, Buenos Aires, Argentina, MD, Medicine

Selected Publications

Peer-Reviewed Original Research Articles
1. Abba M, Hu Y, Levy CC, Gaddis S, Kittrell F, Hill J, Bissonnette R, Brown PH, Medina D, Aldaz CM. Identification of modulated genes by three classes of chemopreventive agents at preneoplastic stages in a p53-null mouse mammary tumor model. Cancer Prev Res 2(2):175-84, 2/2009. PMID: 19174580.
2. Abba M, Hu Y, Levy C, Gaddis S, Kittrell F, Zhang Y, Hill J, Bissonnette R, Medina D, Brown P, Aldaz CM. Transcriptomic signature of the chemopreventive Bexarotene (Rexinoid LGD1069) on mammary gland from three transgenic mouse mammary cancer models. BMC Med Genomics 1(1):40, 9/2008. PMCID: PMC2563021.
3. Yadav N, Cheng D, Richard S, Morel M, Iyer VR, Aldaz CM, Bedford MT. CARM1 promotes adipocyte differentiation by coactivating PPARgamma. EMBO Rep 9(2):193-8, 2/2008. PMCID: PMC2246418.
4. Wu M, Soler DR, Abba MC, Nunez MI, Baer R, Hatzis C, Llombart-Cussac A, Llombart-Bosch A, Aldaz CM. CtIP silencing as a novel mechanism of tamoxifen resistance in breast cancer. Mol Cancer Res 5(12):1285-95, 12/2007. PMID: 18171986.
5. Abba MC, Sun H, Hawkins KA, Drake JA, Hu Y, Nunez MI, Gaddis S, Shi T, Horvath S, Sahin A, Aldaz CM. Breast cancer molecular signatures as determined by SAGE: correlation with lymph node status. Mol Cancer Res 5(9):881-90, 9/2007. PMID: 17855657.
6. Abba M, Fabris VT, Hu Y, Kittrell FS, Cai WW, Donehower LA, Sahin A, Medina D, Aldaz CM. Identification of novel amplification gene targets in mouse and human breast cancer at a syntenic cluster mapping to mouse ch8A1 and human ch13q34. Cancer Res 67(9):4104-12, 5/2007. PMID: 17483321.
7. Abba MC, Hu Y, Sun H, Drake JA, Gaddis S, Baggerly K, Sahin A, Aldaz CM. Gene expression signature of estrogen receptor alpha status in breast cancer. BMC Genomics 6(1):37, 3/2005. PMCID: PMCPMC555753.
8. Hu Y, Sun H, Drake J, Kittrell F, Abba MC, Deng L, Gaddis S, Sahin A, Baggerly K, Medina D, Aldaz CM. From mice to humans: identification of commonly deregulated genes in mammary cancer via comparative SAGE studies. Cancer Res 64(21):7748-55, 11/2004. PMID: 15520179.
9. Yadav N, Lee J, Kim J, Shen J, Hu MC, Aldaz CM, Bedford MT. Specific protein methylation defects and gene expression perturbations in coactivator-associated arginine methyltransferase 1-deficient mice. Proc Natl Acad Sci U S A 100(11):6464-8, 5/2003. PMCID: PMC164469.
10. Aldaz CM, Hu Y, Daniel R, Gaddis S, Kittrell F, Medina D. Serial analysis of gene expression in normal p53 null mammary epithelium. Oncogene 21(41):6366-76, 9/2002. PMID: 12214277.

Last updated: 10/26/2009