Associate Professor, Department of Epigenetics and Molecular Carcinogenesis, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston
Faculty Member, MD Anderson UT Health Graduate School of Biomedical Sciences (GSBS), Houston, TX
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.
|2007||University of Lisbon Medical School and Gulbenkian Institute, Lisbon, PRT, PHD, Biomedical Sciences|
|1999||University of Lisbon School of Sciences, Lisbon, PRT, BS, MS, Molecular Biology and Genetics|
|2008-2015||Postdoctoral Fellow, Genome Integrity, NIH, Bethesda, MD|
|2007-2008||Visiting Fellow, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA|
Assistant Professor, Department of Epigenetics and Molecular Carcinogenesis, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX, 2015 - 2022
Postdoctoral Research Fellow, National Cancer Institute/NIH, Bethesda, MD, 2008 - 2015
Co-Director, Genetics and Epigenetics Core Course, MD Anderson UT Health Graduate School of Biomedical Sciences (GSBS), Houston, TX, 2020 - Present
Member, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, 2016 - Present
Institutional Committee Activities
Member, MD Anderson Core Facility Oversight Board, 2022 - 2025
Member, COVID-19 Task Force Junior Faculty Basic Science Representative, 2020 - 2021
Member, Faculty Academic Review Committee (FARC), 2018 - Present
Member, Junior Faculty Committee, 2018 - Present
Chair, GSBS Student Scholarship Committee, 2018 - 2019
Member, GSBS Executive Committee, 2018 - 2020
Member, Odyssey Committee, 2017 - 2020
Member, GSBS Student Scholarship Committee, 2016 - 2019
Member, Science Park Animal Facility Advisory Committee, 2016 - 2017
Member, Epigenetics & Mol Carcinogenesis GSBS Steering Committee, 2016 - 2017
|2020||Employee Service Award, MD Anderson Cancer Center|
|2019||Faculty Recognition Award, MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences (GSBS)|
|2017||Junior Faculty Scholar, American Society of Hematology (ASH)|
|2017||Andrew Sabin Family Fellow, MD Anderson Cancer Center|
|2017||Finalist for Pew Scholar Award, MD Anderson Cancer Center|
|2016||Sidney Kimmel Scholar Award, Sidney Kimmel Foundation|
|2015||First Time, Tenure-Track Faculty Recruitment Award, Cancer Prevention and Research Institute of Texas (CPRIT)|
|2015||New Faculty Award, MD Anderson Cancer Center Support Grant (CCSG), NCI|
|2013||PAPS Award (Science), Portuguese-American Postgraduate Society|
|2012||Fellows Award for Research Excellence, NIH|
|2007||Science Award for Portuguese Young Researchers, Pulido Valente Foundation and Foundation for Science and Technology|
|2006||EFIS Fellowship Award, European Federation of Immunological Societies|
|2002||PhD Fellowship Award, Foundation for Science and Technology|
|1999||PRODEP Award Scholarship, Portuguese Government|
- Chen Q, Liu B, Zeng Y, Hwang JW, Dai N, Corrêa IR, Estecio MR, Zhang X, Santos MA, Chen T, Cheng X. GSK-3484862 targets DNMT1 for degradation in cells. NAR Cancer 5(2):zcad022, 2023. e-Pub 2023. PMID: 37206360.
- Van HT, Harkins PR, Patel A, Jain AK, Lu Y, Bedford MT, Santos MA. Methyl-lysine readers PHF20 and PHF20L1 define two distinct gene expression-regulating NSL complexes. J Biol Chem 298(3):101588, 2022. e-Pub 2022. PMID: 35033534.
- Veazey KJ, Cheng D, Lin K, Villarreal OD, Gao G, Perez-Oquendo M, Van HT, Stratton SA, Green M, Xu H, Lu Y, Bedford MT, Santos MA. CARM1 inhibition reduces histone acetyltransferase activity causing synthetic lethality in CREBBP/EP300-mutated lymphomas. Leukemia 34(12):3269-3285, 2020. e-Pub 2020. PMID: 32576962.
- Benton CB, Chien KS, Tefferi A, Rodriguez J, Ravandi F, Daver N, Jabbour E, Jain N, Alvarado Y, Kwari M, Pierce S, Maiti A, Hornbaker M, Santos MA, Martinez S, Siguero M, Zblewski D, Al-Kali A, Hogan WJ, Kantarjian H, Pardanani A, Garcia-Manero G. Safety and tolerability of lurbinectedin (PM01183) in patients with acute myeloid leukemia and myelodysplastic syndrome. Hematol Oncol 37(1):96-102, 2019. e-Pub 2018. PMID: 30153704.
- Das P, Veazey KJ, Van HT, Kaushik S, Lin K, Lu Y, Ishii M, Kikuta J, Ge K, Nussenzweig A, Santos MA. Histone methylation regulator PTIP is required to maintain normal and leukemic bone marrow niches. Proc Natl Acad Sci U S A 115(43):E10137-E10146, 2018. e-Pub 2018. PMID: 30297393.
- Zhang H, Li HS, Hillmer EJ, Zhao Y, Chrisikos TT, Hu H, Wu X, Thompson EJ, Clise-Dwyer K, Millerchip KA, Wei Y, Puebla-Osorio N, Kaushik S, Santos MA, Wang B, Garcia-Manero G, Wang J, Sun SC, Watowich SS. Genetic rescue of lineage-balanced blood cell production reveals a crucial role for STAT3 antiinflammatory activity in hematopoiesis. Proc Natl Acad Sci U S A 115(10):E2311-E2319, 2018. e-Pub 2018. PMID: 29463696.
- Kaushik S, Liu F, Veazey KJ, Gao G, Das P, Neves LF, Lin K, Zhong Y, Lu Y, Giuliani V, Bedford MT, Nimer SD, Santos MA. Genetic deletion or small molecule inhibition of the arginine methyltransferase PRMT5 exhibit anti-tumoral activity in mouse models of MLL-rearranged AML. Leukemia 32(2):499-509, 2018. e-Pub 2017. PMID: 28663579.
- Starnes LM, Su D, Pikkupeura LM, Weinert BT, Santos MA, Mund A, Soria R, Cho YW, Pozdnyakova I, Kubec Højfeldt M, Vala A, Yang W, López-Méndez B, Lee JE, Peng W, Yuan J, Ge K, Montoya G, Nussenzweig A, Choudhary C, Daniel JA. A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex. Genes Dev 30(2):149-63, 2016. e-Pub 2016. PMID: 26744420.
- Santos MA, Faryabi RB, Ergen AV, Day AM, Malhowski A, Canela A, Onozawa M, Lee JE, Callen E, Gutierrez-Martinez P, Chen HT, Wong N, Finkel N, Deshpande A, Sharrow S, Rossi DJ, Ito K, Ge K, Aplan PD, Armstrong SA, Nussenzweig A. DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier. Nature 514(7520):107-11, 2014. e-Pub 2014. PMID: 25079327.
- Callen E, Di Virgilio M, Kruhlak MJ, Nieto-Soler M, Wong N, Chen HT, Faryabi RB, Polato F, Santos M, Starnes LM, Wesemann DR, Lee JE, Tubbs A, Sleckman BP, Daniel JA, Ge K, Alt FW, Fernandez-Capetillo O, Nussenzweig MC, Nussenzweig A. 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions. Cell 153(6):1266-80, 2013. e-Pub 2013. PMID: 23727112.
- Daniel JA, Santos MA, Wang Z, Zang C, Schwab KR, Jankovic M, Filsuf D, Chen HT, Gazumyan A, Yamane A, Cho YW, Sun HW, Ge K, Peng W, Nussenzweig MC, Casellas R, Dressler GR, Zhao K, Nussenzweig A. PTIP promotes chromatin changes critical for immunoglobulin class switch recombination. Science 329(5994):917-23, 2010. e-Pub 2010. PMID: 20671152.
- Santos MA, Huen MS, Jankovic M, Chen HT, López-Contreras AJ, Klein IA, Wong N, Barbancho JL, Fernandez-Capetillo O, Nussenzweig MC, Chen J, Nussenzweig A. Class switching and meiotic defects in mice lacking the E3 ubiquitin ligase RNF8. J Exp Med 207(5):973-81, 2010. e-Pub 2010. PMID: 20385748.
- Santos MA, Sarmento LM, Rebelo M, Doce AA, Maillard I, Dumortier A, Neves H, Radtke F, Pear WS, Parreira L, Demengeot J. Notch1 engagement by Delta-like-1 promotes differentiation of B lymphocytes to antibody-secreting cells. Proc Natl Acad Sci U S A 104(39):15454-9, 2007. e-Pub 2007. PMID: 17878313.
- Semedo T, Almeida Santos M, Martins P, Silva Lopes MF, Figueiredo Marques JJ, Tenreiro R, Barreto Crespo MT. Comparative study using type strains and clinical and food isolates to examine hemolytic activity and occurrence of the cyl operon in enterococci. J Clin Microbiol 41(6):2569-76, 2003. PMID: 12791882.
- Semedo T, Santos MA, Lopes MF, Figueiredo Marques JJ, Barreto Crespo MT, Tenreiro R. Virulence factors in food, clinical and reference Enterococci: A common trait in the genus?. Syst Appl Microbiol 26(1):13-22, 2003. PMID: 12747405.
- Van HT, Santos MA. Histone modifications and the DNA double-strand break response. Cell Cycle 17(21-22):2399-2410, 2018. e-Pub 2018. PMID: 30394812.
- Santos MA, John S, Nussenzweig A. Tumor promoting role of the DNA damage response. Cell Cycle 13(18):2807-8, 2014. PMID: 25486465.
- Van H.T., Santos, MA. Chromatin Modifications in the DNA Damage Response. In: Epigenetics and DNA Damage. 1st. Elsevier, 2022.
|Title:||Recruitment of First-time, Tenure-Track Faculty - Dr. Margarida Santos|
|Funding Source:||Cancer Prevention & Research Institute of Texas (CPRIT)|
|Title:||Targeting Protein Arginine Methylation in MLL-fusion AML|
|Funding Source:||Sidney Kimmel Foundation-Kimmel Scholar Award|
|Title:||Tumor Promoting Role of the DNA Damage Response in MLL-fusion Leukemias|
|Funding Source:||American Society of Hematology (ASH)|
|Title:||Tumor Promoting Role of the DNA Damage Response|
|Funding Source:||Andrew Sabin Family Foundation|
|Title:||Epigenetic Regulation of Thrombopoiesis|
|Title:||Roles of Coactivator-Associated Arginine Methyltransferase 1 in B cell activation and lymphomagenesis|
|Title:||Histone H4 tyrosine phosphorylation couples with DNA damage resistance in aggressive leukemia|
|Funding Source:||The Elsa U. Pardee Foundation|
|Title:||Institutional Start-Up Funds|
|Funding Source:||MD Anderson Cancer Center|
|Title:||CCSG New Faculty Award|
|Title:||Roles of Histone H4 Tyrosine 51 Phosphorylation in the Response to DNA Double Strand Breaks|
|Title:||Efficacy of the Staphylococcal Nuclease Inhibitor pdTP in Myeloid Leukemia|
|Title:||Defining the role of a novel histone modification in the response to DNA double strand breaks|
|Funding Source:||IRG, The University of Texas MD Anderson Cancer Center|
|Title:||Roles and Targeting of Methyl-Lysine Readers in Non-Small Cell Lung Cell Lung Cancer|
|Funding Source:||Tobacco Pilot Grant, The University of Texas MD Anderson Cancer Center, Houston, TX|
|Title:||Tobacco Pilot Grant: A Novel Epigenetic Vulnerability in Non-Small Cell Lung Cancer|
|Funding Source:||The University of Texas MD Anderson Cancer Center, Houston, TX|
|Title:||Cockrell Endowment Award|
|Funding Source:||Internal Award, The University of Texas MD Anderson Cancer Center|
|Title:||Roles and Targeting of CARM1 Activity in Diffuse Large B Cell Lymphoma|
|Funding Source:||Leukemia and Lymphoma Society|
|Title:||Roles and Targeting of Staphylococcal Nuclease Domain-containing Protein 1 (SND1) in MLL-rearranged Leukemia|
|Funding Source:||IRG, The University of Texas MD Anderson Cancer Center|
|Title:||Roles of two distinct Non-Specific-Lethal (NSL) complexes in transcriptional regulation|
|Title:||Roles and Targeting of Methyl-Lysine Readers in Non-Small Cell Lung Cancer|
|Funding Source:||Tobacco Pilot Project, The University of Texas MD Anderson Cancer Center|