Margarida Albuquerque Almeida Santos, Ph.D.
Department of Epigenetics and Molecular Carcinogenesis, Division of Discovery Science
Present Title & Affiliation
Primary Appointment
Associate Professor, Department of Epigenetics and Molecular Carcinogenesis, Division of Discovery Science, The University of Texas MD Anderson Cancer Center, Houston
Faculty Member, MD Anderson UT Health Graduate School of Biomedical Sciences (GSBS), Houston, TX
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.
Education & Training
Degree-Granting Education
| 2007 | University of Lisbon Medical School, Lisbon, PT, Ph.D. in Biomedical Sciences |
| 1999 | University of Lisbon School of Sciences, Lisbon, PT, BS, MS in Molecular Biology and Genetics |
Postgraduate Training
| 2008-2015 | Postdoctoral Fellow, Genome Integrity, Natonal Cancer Institute/National Institutes of Health, Bethesda, Maryland |
| 2007-2008 | Visiting Fellow, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania |
Experience & Service
Academic Appointments
Assistant Professor, Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, 2015 - 2022
Administrative Appointments/Responsibilities
Member, Graduate Education Committee (GEC), MD Anderson Cancer Center/UT Health Graduate School of Biomedical Sciences (GSBS), Houston, Texas, 2024 - Present
Member, MD Anderson Core Facility Oversight Board, Houston, TX, 2022 - Present
Member, Institutional Committee, GSBS Executive Committee, The University of Texas MD Anderson Cancer Center, Houston, Texas, 2018 - 2020
Member, Institutional Committee, Faculty Academic Review Committee (FARC), The University of Texas MD Anderson Cancer Center, Houston, Texas, 2018 - Present
Other Appointments/Responsibilities
Co-Director, The University of Texas MD Anderson Cancer Center, 2020 - 2023
Institutional Committee Activities
Chair, Communications Committee, Genetics and Epigenetics Program, GSBS, 2022 - 2023
Member, Communications Committee, Genetics and Epigenetics Program, GSBS, 2022 - Present
Member, Steering Committee, Genetics and Epigenetics Program, GSBS, 2022 - 2023
Review Committee Member, Research Faculty Appointment Committee, Swarnalatha Manickavinayaham, 2022 - Present
Chair, Communications Committee, Genetics and Epigenetics Graduate Program, 2022 - 2024
Member, COVID-19 Task Force Junior Faculty Basic Science Representative, 2020 - 2021
Member, Junior Faculty Committee, 2018 - Present
Chair, GSBS Student Scholarship Committee, 2018 - 2019
Member, Odyssey Committee, 2017 - 2020
Member, Science Park Animal Facility Advisory Committee, 2016 - 2017
Member, GSBS Student Scholarship Committee, 2016 - 2019
Member, Epigenetics & Mol Carcinogenesis GSBS Steering Committee, 2016 - 2017
Honors & Awards
| 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 |
Selected Publications
Peer-Reviewed Articles
- Santos M, Hwang JW, Bedford MT. CARM1 arginine methyltransferase as a therapeutic target for cancer. J Biol Chem 299(9):105124, 2023. e-Pub 2023. PMID: 37536629.
- 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 2019. 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 2018. 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.
Invited Articles
- 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.
Book Chapters
- Van HT, Santos, MA. Chromatin Modifications in the DNA Damage Response. In: Epigenetics and DNA Damage. 1st. Elsevier, 2022.
Selected Presentations & Talks
Local Presentations
- 2022. Targeting Arginine Methylation in B-cell Lymphoma. Distinguished Seminar Series. Houston, Texas, US.
- 2022. Targeting Arginine Methylation in Diffuse Large B Cell Lymphoma. Research Townhall. Houston, Texas, US.
- 2020. Novel Histone Modifications in the DNA Damage Response (Cancelled due to COVID-19). Conference on Genome Repair. Houston, Texas, US.
- 2018. Epigenetic Regulation of Normal and Malignant Hematopoiesis. Annual Retreat. Houston, Texas, US.
- 2016. DNA Damage Response and Epigenetic Regulation Of Leukemia Stem Cells. Exchange Research Seminar Series. Houston, Texas, US.
- 2016. Targeting Protein Arginine Methylation in MLL-rearranged Leukemia. Seminar Series. Houston, Texas, US.
- 2016. Targeting Arginine Methylation in MLL-rearranged Leukemias. Annual Retreat. Round Top, Texas, US.
- 2016. Leukemia Research Series: Epigenetic Targeting of MLL-rearranged Leukemia. Houston, Texas, US.
Regional Presentations
- 2019. Epigenetic Regulation of Normal and Malignant Hematopoiesis. R&D Seminar. Houston, TX, US.
- 2018. Epigenetic Regulation of Normal and Malignant Hematopoiesis. Hematopoiesis and Inflammation Symposium. Houston, TX, US.
- 2017. Targeting Arginine Methylation in MLL-rearranged Leukemias. Houston, TX, US.
- 2014. DNA damage induced differentiation of leukemic cells as an anti-cancer barrier. Houston, TX, US.
National Presentations
- 2023. Targeting Arginine Methylation in B Cell Lymphoma (Virtual Presentation). Normal and Malignant Hematopoiesis Research Affinity Group Meeting, US.
- 2015. DNA damage induced differentiation of leukemic cells as an anti-cancer barrier. Boston, MA, US.
- 2014. DNA damage induced differentiation of leukemic cells as an anti-cancer barrier. Philadelphia, PA, US.
- 2013. MLL4 regulates hematopoietic stem cell function and it is required for MLL-AF9 leukemogenesis. Seminar Series. Bethesda, MD, US.
- 2011. The role of the MLL3/4 histone methyltransferase complex in hematopoietic stem cells. Seminar Series. Bethesda, MD, US.
- 2010. PTIP regulates hematopoietic stem cells. Seminar Series. Bethesda, MD, US.
- 2009. Histone ubiquitilation and class switch recombination in B lymphocytes. Seminar Series. Bethesda, MD, US.
- 2006. Notch is a new regulator of mature B cell activation. Philadelphia, PA, US.
International Presentations
- 2016. Targeting Protein Arginine Methylation in MLL-fusion Leukemia. San Juan, PR.
- 2016. Targeting Protein Arginine Methylation in MLL-fusion Leukemias. Lisbon, PT.
- 2015. Tumor promoting role of the DNA damage response. Lisbon, PT.
- 2015. Tumor promoting role of the DNA damage response. Lisbon, PT.
- 2014. DNA damage induced differentiation of leukemic cells as an anti-cancer barrier. Jena, DE.
- 2006. Notch is a new regulator of mature B cell activation. Lausanne, CH.
- 2005. Notch is a new regulator of mature B cell activation. Pamplona, ES.
Grant & Contract Support
| Date: | 2024 - 2025 |
| Title: | Epigenetic regulation of hematopoietic stem cell to bone-resorbing macrophage differentiation |
| Funding Source: | Adverse Incident Bridget Funding, UTMDACC |
| Role: | PI |
| ID: | 2024-00064118-Y1 |
| Date: | 2024 - 2029 |
| Title: | The Academy at MD Anderson UTHealth Houston Graduate School - Maximizing Opportunities for Training, Development, and Community |
| Funding Source: | NIH/NIGMS |
| Role: | Mentor |
| ID: | T32GM152796-01 |
| Date: | 2024 - 2024 |
| Title: | Roles of two distinct Non-Specific-Lethal (NSL) complexes in transcriptional regulation |
| Funding Source: | UTMDACC, Adverse Incident Bridge Funding |
| Role: | PI |
| ID: | RCTS#2024-00063414-Y1 |
| Date: | 2021 - 2026 |
| Title: | Roles of Coactivator-Associated Arginine Methyltransferase 1 in B cell activation and lymphomagenesis |
| Funding Source: | NIH/NCI |
| Role: | PI |
| ID: | R01CA247883 |
Patient Reviews
CV information above last modified March 06, 2025