C. Marcelo Aldaz, M.D., Ph.D.
Department of Epigenetics and Molecular Carcinogenesis, Division of Discovery Science
Present Title & Affiliation
Primary Appointment
Professor, Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX
Dual/Joint/Adjunct Appointment
Professor, University of Texas Health Science Center, GSBS, Houston, TX
Research Interests
My laboratory has a long-standing interest in human genetics and cancer genomics. Over the years my lab has focused on identifying and elucidating the role of key abnormalities that affect the genome of normal and premalignant cells towards cancer development and evolution. We were among the earliest to utilize high throughput sequencing approaches (serial analysis of gene expression) for functional genomics studies. We performed comprehensive studies for characterizing the genome, transcriptome and methylome of breast ductal carcinoma in situ (DCIS) lesions identifying key driver mutations, epigenetic changes and gene expression alterations that occur at pre-invasive stages of breast cancer progression. Among other studies, my lab was the first to clone and characterize a putative tumor suppressor gene which we named WWOX (WW domain containing oxidoreductase), target of chromosomal fragile site 16D (FRA16D). WWOX is one of the largest human genes and FRA16D is the second most common site in the human genome for spontaneous chromosomal breakage and rearrangement. Germline and somatic copy number variation affecting the WWOX locus are common and intimately linked to an array of diverse human pathologies. My laboratory has published extensively on WWOX’s role in multiple diseases from cancer, metabolic conditions to CNS pathology. We have generated various molecular biology tools and reagents including valuable genetically engineered mouse models to analyze the effects of targeted Wwox ablation in tissues of relevance and knock-in mutations not only to understand the role of WWOX in cancer but now in rapidly emerging new fields of various pathologies associated with WWOX. Recently we and others have discovered that germline WWOX loss-of-function mutations are causally linked to various complex neurodevelopmental disorders including spinocerebellar ataxia, autosomal recessive type 12 (SCAR12, MIM #614322 ), developmental and epileptic encephalopathy 28 ( DEE28, MIM#616211), developmental delay, intellectual disability and Autism Spectrum Disorders. Importantly, WWOX has been recently identified as a novel risk gene for, Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. Thus, the spectrum of complex brain disorders associated with WWOX is broad and heterogeneous, and there is little understanding of potential mechanisms at play. We are currently aiming to understand how WWOX loss-of-function is mechanistically related to disruption of the excitatory/inhibitory neuronal homeostasis in the neocortex and cerebellum. PUBLICATIONS
Education & Training
Degree-Granting Education
| 1983 | University of Buenos Aires Medical School, Buenos Aires, ARG, PHD, Doctor in Medical Sciences |
| 1980 | University of Buenos Aires Medical School, Buenos Aires, ARG, MD, Medicine |
Selected Publications
Peer-Reviewed Articles
- Hussain T, Sanchez K, Crayton J, Saha D, Jeter C, Lu Y, Abba M, Seo R, Noebels JL, Fonken L, Aldaz CM. WWOX P47T partial loss-of-function mutation induces epilepsy, progressive neuroinflammation, and cerebellar degeneration in mice phenocopying human SCAR12. Prog Neurobiol 223:102425, 2023. e-Pub 2023. PMID: 36828035.
- Fabre ML, Canzoneri R, Gurruchaga A, Lee J, Tatineni P, Kil H, Lacunza E, Aldaz CM, Abba MC. MALINC1 an Immune-Related Long Non-Coding RNA Associated with Early-Stage Breast Cancer Progression. Cancers (Basel) 14(12), 2022. e-Pub 2022. PMID: 35740485.
- Park D, Gharghabi M, Reczek CR, Plow R, Yungvirt C, Aldaz CM Huebner K. Wwox Binding to the Murine Brca1-BRCT Domain Regulates Timing of Brip1 and CtIP Phospho-Protein Interactions with This Domain at DNA Double-Strand Breaks, and Repair Pathway Choice. Int J Mol Sci 23(7), 2022. e-Pub 2022. PMID: 35409089.
- Park D, Gharghabi M, Schrock MS, Plow R, Druck T, Yungvirt C, Aldaz CM, Huebner K. Interaction of Wwox with Brca1 and associated complex proteins prevents premature resection at double-strand breaks and aberrant homologous recombination. DNA Repair (Amst) 110:103264, 2022. e-Pub 2021. PMID: 34998176.
- Ferretti VA, Canzoneri R, Palma S, Lacunza E, Aldaz CM, Abba MC. RHBDD2-WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells. Oncol Rep 46(2), 2021. e-Pub 2021. PMID: 34109992.
- Trinh A, Gil Del Alcazar CR, Shukla SA, Chin K, Chang YH, Thibault G, Eng J, Jovanovic B, Aldaz CM, Park SY, Jeong J, Wu C, Gray J, Polyak K. Genomic alterations during the in situ to invasive ductal breast carcinoma transition shaped by the immune system. Mol Cancer Res 19(4):623-635, 2021. e-Pub 2020. PMID: 33443130.
- Abba MC, Fabre ML, Lee J, Tatineni P, Kil H, Aldaz CM. HOTAIR Modulated Pathways in Early-Stage Breast Cancer Progression. Front Oncol 11:783211, 2021. e-Pub 2021. PMID: 34869037.
- Zeng Z, Chen W, Moshensky A, Shakir Z, Khan R, Crotty Alexander LE, Ware LB, Aldaz CM, Jacobson JR, Dudek SM, Natarajan V, Machado RF, Singla S. Cigarette Smoke and Nicotine-Containing E-cigarette Vapor Downregulate Lung WWOX Expression Which is Associated with Increased Severity of Murine ARDS. Am J Respir Cell Mol Biol 64(1):89-99, 2021. e-Pub 2020. PMID: 33058734.
- Aldaz CM,, Hussain T. WWOX Loss of Function in Neurodevelopmental and Neurodegenerative Disorders. Int J Mol Sci 21(23), 2020. e-Pub 2020. PMID: 33255508.
- Abba MC, Canzoneri R, Gurruchaga A, Lee J, Tatineni P, Kil H, Lacunza E, Aldaz CM. LINC00885 a Novel Oncogenic Long Non-Coding RNA Associated with Early Stage Breast Cancer Progression. Int J Mol Sci 21(19), 2020. e-Pub 2020. PMID: 33049922.
- Hussain T, Liu B, Shrock MS, Williams T, Aldaz CM. WWOX, the FRA16D gene: a target of and a contributor to genomic instability. Genes Chromosomes Cancer 58(5):324-338, 2019. e-Pub 2018. PMID: 30350478.
- Hussain T, Kil H, Hattiangady B, Lee J, Kodali M, Shuai B, Attaluri S, Takata Y, Shen J, Abba MC, Shetty AK, Aldaz CM. Wwox deletion leads to reduced GABA-ergic inhibitory interneuron numbers and activation of microglia and astrocytes in mouse hippocampus. Neurobiol Dis 121:163-176, 2019. e-Pub 2018. PMID: 30290271.
- McBride KM, Kil H, Mu Y, Plummer JB, Lee J, Zelazowski MJ, Sebastian M, Abba MC, Aldaz CM. Wwox Deletion in Mouse B Cells Leads to Genomic Instability, Neoplastic Transformation, and Monoclonal Gammopathies. Front Oncol 9:517, 2019. e-Pub 2019. PMID: 31275852.
- Visschedijk MC, Spekhorst LM, Cheng SC, van Loo ES, Jansen BHD, Blokzijl T, Kil H, de Jong DJ, Pierik M, Maljaars JPWJ, van der Woude CJ, van Bodegraven AA, Oldenburg B, Löwenberg M, Nieuwenhuijs VB, Imhann F, van Sommeren S, Alberts R, Xavier RJ, Dijkstra G, Nico Faber K, Aldaz CM, Weersma RK, Festen EAM. Genomic and expression analyses identify a disease modifying variant for fibrostenotic Crohn's disease. J Crohns Colitis 12(5):582-588, 2018. e-Pub 2018. PMID: 29361163.
- Hussain T, Lee J, Abba MC, Chen J, Aldaz CM. Delineating WWOX protein interactome by tandem affinity purification mass-spectrometry: Identification of top interactors and key metabolic pathways involved. Front Oncol 8(591):591, 2018. e-Pub 2018. PMID: 30619736.
- Schrock MS, Batar B, Lee J, Druck T, Ferguson B, Cho JH, Akakpo K, Hagrass H, Heerema NA, Xia F, Parvin JD, Aldaz CM, Huebner K. Wwox-Brca1 interaction: Role in DNA repair pathway choice. Oncogene 36(16):2215-2227, 2017. e-Pub 2016. PMID: 27869163.
- Abba MC, Zhong Y, Lee J, Kil H, Lu Y, Takata Y, Simper MS, Gaddis S, Shen J, Aldaz CM. DMBA induced mouse mammary tumors display high incidence of activating Pik3caH1047 and loss of function Pten mutations. Oncotarget 7(39):64289-64299, 2016. e-Pub 2016. PMID: 27588403.
- Abba MC, Gong T, Lu Y, Lee J, Zhong Y, Lacunza E, Butti M, Takata Y, Gaddis S, Shen J, Estecio MR, Sahin AA, Aldaz CM. A Molecular Portrait of High-Grade Ductal Carcinoma In Situ. Cancer Res 75(18):3980-90, 2015. e-Pub 2015. PMID: 26249178.
- Aldaz CM, Ferguson BW, Abba MC. WWOX At The Crossroads of Cancer, Metabolic Syndrome Related Traits And CNS Pathologies. Biochim Biophys Acta 1846(1):188-200, 2014. e-Pub 2014. PMID: 24932569.
- Iatan I, Choi HY, Ruel I, Reddy MV, Kil H, Lee J, Odeh MA, Salah Z, Abu-Remaileh M, Weissglas-Volkov D, Nikkola E, Civelek M, Awan Z, Croce CM, Aqeilan RI, Pajukanta P, Aldaz CM, Genest J. The WWOX gene modulates high-density lipoprotein and lipid metabolism. Circ Cardiovasc Genet 7(4):491-504, 2014. e-Pub 2014. PMID: 24871327.
- Lacunza E, Rabassa ME, Canzoneri R, Pellon-Maison M, Croce MV, Aldaz CM, Abba MC. Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein response. Cell Stress Chaperones 19(3):379-88, 2014. e-Pub 2013. PMID: 24078384.
- Mallaret M, Synofzik M, Lee J, Sagum CA, Mahajnah M, Sharkia R, Drouot N, Renaud M, Klein FA, Anheim M, Tranchant C, Mignot C, Mandel JL, Bedford M, Bauer P, Salih MA, Schüle R, Schöls L, Aldaz CM, Koenig M. The tumour suppressor gene WWOX is mutated in autosomal recessive cerebellar ataxia with epilepsy and mental retardation. Brain 137(2):411-9, 2014. e-Pub 2013. PMID: 24369382.
- Stewart DJ, Nunez MI, Jelinek J, Hong D, Gupta S, Aldaz CM, Issa JP, Kurzrock R, Wistuba II. Impact of decitabine on immunohistochemistry expression of the putative tumor suppressor genes FHIT, WWOX, FUS1 and PTEN in clinical tumor samples. Clin Epigenetics 6(1):13, 2014. e-Pub 2014. PMID: 25024751.
- Bloomfield M, McCormack A, Mandrioli D, Fiala C, Aldaz CM, Duesberg P. Karyotypic evolutions of cancer species in rats during the long latent periods after injection of nitrosourea. Mol Cytogenet 7(1):71, 2014. e-Pub 2014. PMID: 25614763.
- Ferguson BW, Gao X, Zelazowski MJ, Lee J, Jeter CR, Abba MC, Aldaz CM. The cancer gene WWOX behaves as an inhibitor of SMAD3 transcriptional activity via direct binding. BMC Cancer 13:593, 2013. e-Pub 2013. PMID: 24330518.
- Ferguson BW, Gao X, Kil H, Lee J, Benavides F, Abba MC, Aldaz CM. Conditional Wwox deletion in Mouse Mammary Gland by Means of Two Cre Recombinase Approaches. PLoS One 7(5):e36618, 2012. e-Pub 2012. PMID: 22574198.
- Ludes-Meyers JH, Kil H, Parker-Thornburg J, Kusewitt DF, Bedford MT, Aldaz CM. Generation and Characterization of Mice Carrying a Conditional Allele of the Wwox Tumor Suppressor Gene. PLoS One 4(11):e7775, 2009. e-Pub 2009. PMID: 19936220.
- 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, 2007. PMID: 18171986.
- 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, 2007. PMID: 17483321.
- Pimenta FJ, Gomes DA, Perdigao PF, Barbosa AA, Romano-Silva MA, Gomez MV, Aldaz CM, De Marco L, Gomez RS. Characterization of the tumor suppressor gene WWOX in primary human oral squamous cell carcinomas. Int J Cancer 118(5):1154-8, 2006. PMID: 16152610.
- Ramos D, Aldaz CM. WWOX, a chromosomal fragile site gene and its role in cancer. Adv Exp Med Biol 587:149-59, 2006. PMID: 17163164.
- Thavathiru E, Ludes-Meyers JH, MacLeod MC, Aldaz CM. Expression of common chromosomal fragile site genes, WWOX/FRA16D and FHIT/FRA3B is downregulated by exposure to environmental carcinogens, UV, and BPDE but not by IR. Mol Carcinog 44(3):174-82, 2005. PMID: 16187332.
- Nunez MI, Rosen DG, Ludes-Meyers JH, Abba MC, Kil H, Page R, Klein-Szanto AJ, Godwin AK, Liu J, Mills GB, Aldaz CM. WWOX protein expression varies among ovarian carcinoma histotypes and correlates with less favorable outcome. BMC Cancer 5(1):64, 2005. PMID: 15982416.
- Gourley C, Paige AJ, Taylor KJ, Scott D, Francis NJ, Rush R, Aldaz CM, Smyth JF, Gabra H. WWOX mRNA expression profile in epithelial ovarian cancer supports the role of WWOX variant 1 as a tumour suppressor, although the role of variant 4 remains unclear. Int J Oncol 26(6):1681-9, 2005. PMID: 15870886.
- Nunez MI, Ludes-Meyers J, Abba MC, Kil H, Abbey NW, Page RE, Sahin A, Klein-Szanto AJ, Aldaz CM. Frequent loss of WWOX expression in breast cancer: correlation with estrogen receptor status. Breast Cancer Res Treat 89(2):99-105, 2005. PMID: 15692750.
- Donehower LA, Godley LA, Aldaz CM, Pyle R, Shi YP, Pinkel D, Gray J, Bradley A, Medina D, Varmus HE. The role of p53 loss in genomic instability and tumor progression in a murine mammary cancer model. Prog Clin Biol Res 395:1-11, 1996. PMID: 8895979.
Abstracts
- Nunez MI, Ludes-Meyers JH, Kil H, Rosen D, Klein-Szanto A, Liu J, Godwin AK, Mills G, Aldaz CM. The putative tumor suppressor WWOX protein is normally expressed in surface ovarian epithelium and frequently lost in ovarian carcinomas. Proc Am Assoc Cancer Res 45:4429, 2004.
Book Chapters
- Ludes-Meyers JH, Nunez MI, Aldaz CM. WWOX, the target of common chromosomal fragile site, FRA16D, is frequently dysregulated in multiple tumor types. In: Fragile Sites: New Discoveries and Changing Perspectives. Nova Science Publishers: Hauppauge, NY, 241-60, 2007.
Grant & Contract Support
| Title: | Characterization of early breast cancer driver IncRNAs |
| Funding Source: | Department of Defense (DOD) |
| Role: | Principal Investigator |
| Title: | Pilot Evaluation of Epigenomic and Immunologic States in Current and Former Tobacco Smokers |
| Funding Source: | Tobacco Pilot Award, The University of Texas MD Anderson Cancer Center |
| Role: | Principal Investigator |
| Title: | Targeted casein kinase 1δ (CK1δ) inhibition as a breast cancer prevention strategy |
| Funding Source: | NCI Preclinical PREVENT Cancer Program |
| Role: | Principal Investigator |
| Title: | Role of WWOX Loss of Function in High Risk Multiple Myeloma |
| Funding Source: | Leukemia and Lymphoma Society |
| Role: | Project Leader |
Patient Reviews
CV information above last modified November 11, 2024