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Faculty Profile Last Modified Time: 12:37:10 PM Wed, 27 May 2020   Contact Information Margarida Almeida Santos Associated Profiles  Assistant Professor, Epigenetics and Molecular Carcinogenesis, UT MD Anderson Cancer Center     MIAlmeidaSantos@mdanderson.org     713-834-6262    Web Link    Lab Webpage    Genetic Recombination, Immunoglobulin Class Switching, DNA Damage, Histones, Leukemia, Chromatin, Enterococcus, PM 01183    Associated Profiles Professional Preparation Research and Expertise Affiliations Appointments  Professional Preparation  Degree Major Institution Year  PhD Biomedical Sciences, Immunology University of Lisbon 2007  BS/MS Molecular Biology and Genetics University of Lisbon 1999  Research and Expertise Research Interests   My scientific interests are focused on replicative stress/DNA damage response and epigenetic regulators in stem cell cancer. Current studies in my laboratory focus on the hematopoietic system, since 1) it is a well-established system for adult stem cells studies and 2) the dynamic nature of the hematopoietic system places it in a vulnerable position with respect to genomic damage during DNA replication. Replicative stress can be defined as a slowing or stalling of replication fork progression and a source of spontaneous DNA lesions that drives genomic instability. "Oncogene-induced" replicative stress is a major driving force of hematological cancers. Aberrant oncogene expression induces precocious entry into S phase and perturbs replication fork progression, triggering the DNA damage response. The classical view of the DNA damage response (DDR) postulates that DDR is a crucial tumorigenesis barrier in early stages of cancer development, and a selective pressure that favors malignant clones with defects in DNA repair factors. My recent work showed that DNA damage induces the differentiation of leukemic stem-like cells in acute myeloid leukemia (AML) harboring the MLL-AF9 oncogene, thus uncovering an unexpected tumor-promoting role of genome guardians in enforcing the oncogene-induced differentiation blockade in AML (Santos et al., Nature 2014). Current studies in my laboratory explore the concept of "DNA damage-induced differentiation of stem-like cancer cells" in AML and other aggressive hematological malignancies using mouse models, next generation sequencing and various DNA damage treatments and assays. Elucidating which DNA damage response proteins should be targeted in order to promote effective differentiation of leukemic stem cells is the next important step in designing new therapies against these cancers.  Publications/Creative Works Click here to search for this faculty member's publications on PubMed.  Affiliations  Research Consortia Gulf Coast Consortia Immunology Cluster  Appointments Title Department / School Institution Assistant Professor Epigenetics and Molecular Carcinogenesis UT MD Anderson Cancer Center Faculty Member Graduate School of Biomedical Sciences UT Health Science Center Houston

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