C. Marcelo Aldaz, M.D., Ph.D.
Department of Epigenetics and Molecular Carcinogenesis, Division of Discovery Science
About Dr. Aldaz
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 the potential mechanisms at play. We are currently aiming to understand how WWOX loss-of-function is mechanistically related to disruption of excitatory/inhibitory neuronal homeostasis in the neocortex and cerebellum.
Present Title & Affiliation
Primary Appointment
Professor, Division of Discovery Science, University of Texas Health Science Center, GSBS, Houston, TX
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
Professor, Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, 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 the potential mechanisms at play. We are currently aiming to understand how WWOX loss-of-function is mechanistically related to disruption of excitatory/inhibitory neuronal homeostasis in the neocortex and cerebellum.
Education & Training
Degree-Granting Education
| 1983 | University of Buenos Aires Medical School, Buenos Aires, AR, Doctor in Medical Sciences, Ph.D |
| 1980 | University of Buenos Aires Medical School, Buenos Aires, AR, MD |
Postgraduate Training
| 1984-1985 | Project Investigator, The University of Texas Cancer Center, Smithville, Texas |
| 1983-1984 | Robert A. Welch Foundation Postdoctoral Fellow, The University of Texas Cancer Center, Smithville, Texas |
| 1980-1983 | Research Fellow, Atomic Energy Commission, Buenos Aires |
Experience & Service
Academic Appointments
Associate Professor, Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville, TX, 1995 - 2001
Assistant Professor, Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Smithville, TX, 1989 - 1995
Administrative Appointments/Responsibilities
Co-Director, Department of Center for Environmental and Molecular Carcinogenesis (CEMC), The University of Texas MD Anderson Cancer Center, Smithville, TX, 2012 - 2016
Other Appointments/Responsibilities
Associate Member, Livestrong Cancer Institutes, Dell Medical School, The University of Texas at Austin, Austin, TX, 2019 - Present
Consultant, Bayer Medical Oncology Division, Houston, Texas, 2002 - 2003
Faculty Member, Center for Molecular Carcinogenesis and Toxicology (CMTC), The University of Texas at Austin, Austin, TX, 2000 - Present
Assistant Biologist, Science Park- Research Division, The University of Texas M.D. Anderson Cancer Center, Smithville, TX, 1987 - 1988
Research Associate, Department of Carcinogenesis, Science Park- Research Division, The University of Texas M.D. Anderson Cancer Center, Smithville, TX, 1985 - 1986
Project Investigator, Science Park- Research Division, The University of Texas MD Anderson Cancer Center, Smithville, TX, 1983 - 1985
Research Fellow, Atomic Energy Commission, Buenos Aires, 1980 - 1983
Institutional Committee Activities
Member, Research Integrity Matter MDA 2023-11 Inquiry Committee, 2024 - Present
Judge, Oral Skills Presentation competition for GSBS Student Research Day (GSRD), 2019
Member, MDACC, DCIS Tissue Utilization Committee, 2018
Basic Committee Reviewer, MDACC, Institutional Research Grant (IRG) Committee, 2017 - Present
Member, MDACC, Multidisciplinary Research Advisory Committee (MRAC), 2016 - 2023
Member, MDACC, Institutional Biosafety Committee, 2011 - 2015
Member, Department of Epigenetics and Molecular Carcinogenesis, ARFAC Committee, 2010
Representative, Department of Molecular Carcinogenesis, Faculty Senate Department, 2010 - 2012
Member, GSBS Molecular Carcinogenesis Program, Steering Committee, 2010 - 2011
Member, GSBS Molecular Carcinogenesis Program, Academic Affairs Committee, 2010 - 2014
Member, GSBS Molecular Carcinogenesis Program, Student Admissions Committee, 2010 - 2013
Member, Department of Molecular Carcinogenesis, Hogg Seminar Series Committee, 2006 - 2012
Member, Department of Epigenetics and Molecular Carcinogenesis, Information Resources Advisory Committee, 2005
Member, Department of Molecular Carcinogenesis, Seminar Committee, 2003 - 2006
Member, Department of Epigenetics and Molecular Carcinogenesis, Tenure & Promotions Committee, 2001
Member, Department of Molecular Carcinogenesis, Library Committee, 1999 - 2010
Member, Department of Molecular Carcinogenesis, Cancer Genomics Committee, 1999
Member, GSBS Molecular Carcinogenesis Program, Admissions Committee, 1999 - 2002
Member, Department of Epigenetics and Molecular Carcinogenesis, Shared Resources Committee, 1998
Member, Department of Molecular Carcinogenesis, IACUC Committee, 1992 - 2005
Member, Department of Molecular Carcinogenesis, Faculty Search Committee, 1990 - 1994
Member, Department of Molecular Carcinogenesis, Graduate Education Committee, 1990 - 1999
Member, Department of Epigenetics and Molecular Carcinogenesis, Various Faculty Search Committees, 1989
Member, Department of Molecular Carcinogenesis, Postdoctoral Training Grant Committee, 1988 - 2001
Honors & Awards
| 1980 | Graduated with Highest Honors from the University of Buenos Aires Medical School |
Professional Memberships
Selected Publications
Peer-Reviewed Articles
- Zeng Z, Abdelwahid E, Chen W, Ascoli C, Pham T, Jacobson JR, Dudek SM, Natarajan V, Aldaz CM, Machado RF, Singla S. Endothelial Knockdown of the Tumor Suppressor, WWOX, Increases Inflammation in Ventilator-Induced Lung Injury. Am J Physiol Lung Cell Mol Physiol 326(6):L687-L697, 2024. e-Pub 2024. PMID: 38563965.
- 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 2022. 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 2021. PMID: 33443130.
- 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 2021. PMID: 33058734.
- 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.
- 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, 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 2019. 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, JPWJ M, 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 2017. 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.
Other Articles
- Aldaz CM, Hussain T WWOX Loss of Function in Neurodevelopmental and Neurodegenerative Disorders. Int J Mol Sci 21(23), 2020. PMID: 33255508.
- 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. PMID: 30350478.
Abstracts
- Gomes MT, Chen J, Polidoro R, Bai Y, Prohaska C, Singla S, Aldaz CM, Stearman R, Machado R. Abstract 17443: Wwox is a Critical Regulator of Pulmonary Artery Smooth Muscle Cell Homeostasis. Circulation 148(A17443-A), 2023. e-Pub 2023.
- Moghaddam SJ, Hussain T, Zarghooni M, Velasco MV, Phan L, Savage MI, Fox JT, Sei S, Brown PH, Aldaz CM. Abstract A012: Repurposing of the macrolide antibiotic clarithromycin for the prevention of lung cancer. Cancer Prev Res (Phila) 15(12_Supplement_2), 2022. e-Pub 2022.
- Chen W, Hussain T, Chen J, Jacobson JR, Dudek SM, Aldaz CM, Singla S. SARS-CoV-2 Spike Protein Binds WWOX and Increases Endothelial Permeability (abstract). Am J Respir Crit Care Med 2022(205):A3197, 2022. e-Pub 2022.
- Trinh A, Gil Del Alcazar CR, Shukla SA, Chin K, Chen YH, Thibault G, Eng J, Jovanovic B, Aldaz CM, Park SY, Jong J, Wu C, Gray J, Polyak K. Abstract PO-059: The genomic landscape of the in situ to invasive ductal breast carcinoma transition shaped by the immune system. Cancer Res 80(21_Supplement):PO-059, 2020. e-Pub 2020.
Grant & Contract Support
| Date: | 2023 - 2025 |
| Title: | Modulation of Neuroimmune Pathways by WWOX: Implications for Complex Brain Disorders |
| Funding Source: | UTMDACC / Adverse Incident Bridge Funding |
| Role: | PI |
| ID: | RCTS 2022-00060708-Y1 |
Patient Reviews
CV information above last modified May 07, 2025