Faculty

M. Andres Blanco, PhD

Graduate Group Affiliations

Contact information

Email:
ablanco@vet.upenn.edu

Publications

Search PubMed for articles

Education:
BA (Biological Sciences, Philosophy)
Cornell University, 2004.
PhD (Molecular Biology)
Princeton University, 2011.

Links
Search PubMed for articles

Permanent link

> Perelman School of Medicine > Faculty > Details

Description of Other Expertise

KEYWORDS: chromatin, epigenetics, cancer, cell identity, acute myeloid leukemia, differentiation therapy, epigenetic memory

Description of Research Expertise

The cells of different tissues have the same genome but are phenotypically distinct. Cell identity programs are thus epigenetic in nature, as they are not driven by changes in the underlying DNA sequence. How do these epigenetic processes work, and why are we so interested in and fascinated by them?

We study the contribution of chromatin states to epigenetic programs. Covalent modifications of histones and DNA offer a powerful mode for encoding and propagating epigenetic information. Long-standing models of lineage specification propose that epigenetic processes help enforce cell fate decisions and maintain differentiated cellular identities. However, the mechanisms by which transient stimuli are converted into stable cell fate outputs are poorly understood. How are cell identity gene expression programs faithfully propagated over time and across the cell cycle? What is the molecular logic that allows stem cells to differentiate but precludes de-differentiation of mature cells? What are the “locking” factors that impose a given cellular identity, and can they be manipulated to induce cellular plasticity?

These problems of basic cellular biology have significant health ramifications. Cancers such as acute myeloid leukemia (AML) are poorly differentiated and driven by cancer stem cells. The induction of latent differentiation programs represents a powerful therapeutic approach for these malignancies, but is hampered by our limited understanding of how epigenetic factors constrain cellular plasticity. A deeper understanding of this process will advance our ability to manipulate cellular identity in selected pathologies. By using a combination of genetic screening, epigenomic profiling, and chromatin-focused biochemistry, we aim to address these and related questions on the epigenetic basis of cellular identity.

LAB PERSONNEL:

M. Andres Blanco, PhD
Haitao Li, PhD
Ricardo Petroni, PhD
Christine Griffiths, BA
Fangxue (Yumi) Yan, BA
Zvi Cramer, BA
Joshua Rico

Selected Publications

Yan F, Li J, Milosevic J, Petroni R, Liu S, Shi Z, Yuan S, Reynaga JM, Qi Y, Rico J, Yu S, Liu Y, Rokudai S, Palmisiano N, Meyer SE, Sung PJ, Wan L, Lan F, Garcia BA, Stanger BZ, Sykes DB, Blanco MA: KAT6A and ENL form an epigenetic transcriptional control module to drive critical leukemogenic gene expression programs. Cancer Discovery December 2021.

Blanco MA*#, Sykes DB, Gu L, Wu M, Cheloufi S, Petroni R, Karnik R, Wawer M, Rico J, Li H, Jacobus WD, Jambhekar A, Meissner A, Hoechedlinger K, Scadden DT*, Shi Y* *Co-corresponding authors #Lead contact: Chromatin state barriers support an irreversible cell fate decision. Cell Reports 37(5), November 2021.

Li J, Yuan S, Norgard RJ, Yan F, Sun YH, Kim IK, Merrell AJ, Sela Y, Jiang Y, Bhanu NV, Garcia BA, Vonderheide RH, Blanco A, Stanger BZ: Epigenetic and transcriptional control of the epidermal growth factor receptor (EGFR) regulates the tumor immune microenvironment in pancreatic cancer. Cancer Discovery 11(3), March 2021.

Benallegue N, Kapoor R, Kebir H, Crockett A, Cheslow L, Abdel-Hakeem MS, Gesualdi J, Miller MC, Wherry J, Church M, Blanco MA, Alvarez JI: The Hedgehog pathway suppresses CD4 T cell driven neuroinflammation. Brain 144(6), July 2021.

Zee BM, Poels KE, Yao C, Jacobus WD, Senior E, Jambhekar A, Lovitch SB, Dhall A, Ma J, Endress JE, Harris IS, Blanco MA, Haigis MC, Michor F, Licht JD, Shi Y : Combined epigenetic and metabolic treatments overcome differentiation blockade in AML. iScience 24(6), May 2021.

Singh S, Kumar S, Srivastava RK, Nandi A, Thacker G, Murali H, Kim S, Baldeon M, Tobias J, Blanco MA, Saffie R, Zaidi MR, Sinha S, Busino L, Fuchs SY, Chakrabarti R.: Loss of ELF5-FBXW7 stabilizes IFNGR1 to promote the growth and metastasis of triple-negative breast cancer through interferon-γ signalling. Nat Cell Biol 22(5), May 2020.

Li J, Yuan S, Norgard RJ, Yan F, Yamazoe T, Blanco A, Stanger BZ: Tumor cell-intrinsic USP22 suppresses antitumor immunity in pancreatic cancer. Cancer Immunol Res 8(3), March 2020.

Celia-Terrasa T, Bastian C, Liu D, Ell B, Aillo NM, Wei Y, Zamalloa J, Blanco MA, Hang X, Kunisky D, Li W, Williams ED, Rabitz H, Kang Y : Hysteresis control of epithelial-mesenchymal transition dynamics conveys a distinct program with enhanced metastatic ability. Nature Communications 9(1), November 2018.

Anastas JN, Zee BM, Kalin JH, Kim M, Guo R, Alexandrescu S, Blanco MA, Giera S, Gillespie SM, Das J, Wu M, Nocco S, Bonal DM, Nguyen QD, Suva ML, Bernstein BE, Alani R, Golub TR, Cole PA, Filbin MG, Shi Y.: Re-programing Chromatin with a Bifunctional LSD1/HDAC Inhibitor Induces Therapeutic Differentiation in DIPG. Cancer Cell 36: 528-544, Nov 2019.

Blanco, M. A., Kang, Y.: Signaling pathways in breast cancer metastasis - novel insights from functional genomics [PMID 21457525] Breast Cancer Res 13(2): 206, 2011.

Hu, G., Chong, R. A., Yang, Q., Wei, Y., Blanco, M. A., Li, F., Reiss, M., Au, J. L., Haffty, B. G., Kang, Y.: MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer [PMID 19111877] Cancer Cell 15(1): 9-20, 2009.

Wan, L., Lu, X., Yuan, S., Wei, Y., Guo, F., Shen, M., Yuan, M., Chakrabarti, R., Hua, Y., Smith, H. A., Blanco, M. A., Chekmareva, M., Wu, H., Bronson, R. T., Haffty, B. G., Xing, Y., Kang, Y.: MTDH-SND1 interaction is crucial for expansion and activity of tumor-initiating cells in diverse oncogene- and carcinogen-induced mammary tumors [PMID 24981741] Cancer Cell 26(1): 92-105, 2014.

Zheng, H., Shen, M., Zha, Y. L., Li, W., Wei, Y., Blanco, M. A., Ren, G., Zhou, T., Storz, P., Wang, H. Y., Kang, Y.: PKD1 phosphorylation-dependent degradation of SNAIL by SCF-FBXO11 regulates epithelial-mesenchymal transition and metastasis [PMID 25203322] Cancer Cell 26(3): 358-373, 2014.

Alpatov, R., Lesch, B. J., Nakamoto-Kinoshita, M., Blanco, A., Chen, S., Stutzer, A., Armache, K. J., Simon, M. D., Xu, C., Ali, M., Murn, J., Prisic, S., Kutateladze, T. G., Vakoc, C. R., Min, J., Kingston, R. E., Fischle, W., Warren, S. T., Page, D. C., Shi, Y.: A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response [PMID 24813610] Cell 157(4): 869-81, 2014.

Greer, E. L., Blanco, M. A., Gu, L., Sendinc, E., Liu, J., Aristizabal-Corrales, D., Hsu, C. H., Aravind, L., He, C., Shi, Y.: DNA Methylation on N6-Adenine in C. elegans [PMID 25936839] Cell 161(4): 868-78, 2015.

Blanco, M. A., LeRoy, G., Khan, Z., Aleckovic, M., Zee, B. M., Garcia, B. A., Kang, Y.: Global secretome analysis identifies novel mediators of bone metastasis [PMID 22688892] Cell Res 22(9): 1339-55, 2012.

Leroy, G., Dimaggio, P. A., Chan, E. Y., Zee, B. M., Blanco, M. A., Bryant, B., Flaniken, I. Z., Liu, S., Kang, Y., Trojer, P., Garcia, B. A.: A quantitative atlas of histone modification signatures from human cancer cells [PMID 23826629] Epigenetics Chromatin 6(1): 20, 2013.

LeRoy, G., Chepelev, I., DiMaggio, P. A., Blanco, M. A., Zee, B. M., Zhao, K., Garcia, B. A.: Proteogenomic characterization and mapping of nucleosomes decoded by Brd and HP1 proteins [PMID 22897906] Genome Biol 13(8): R68, 2012.

Wang, Q., Turlington, A., Heo, S., Blanco, A., Tian, J., Xie, Z., Yan, B., Wan, Y.: Extracellular matrix activity and caveolae events contribute to cell surface receptor activation that leads to MAP kinase activation in response to UV irradiation in cultured human keratinocytes [PMID 15754025] Int J Mol Med 15(4): 633-40, 2005.

Blanco, M. A., Aleckovic, M., Hua, Y., Li, T., Wei, Y., Xu, Z., Cristea, I. M., Kang, Y.: Identification of staphylococcal nuclease domain-containing 1 (SND1) as a Metadherin-interacting protein with metastasis-promoting functions [PMID 21478147] J Biol Chem 286(22): 19982-92, 2011.

Blanco, M. A., Sherman, P. W.: Maximum longevities of chemically protected and non-protected fishes, reptiles, and amphibians support evolutionary hypotheses of aging [PMID 15888334] Mech Ageing Dev 126(6-7): 794-803, 2005.

Chakrabarti, R., Hwang, J., Andres Blanco, M., Wei, Y., Lukacisin, M., Romano, R. A., Smalley, K., Liu, S., Yang, Q., Ibrahim, T., Mercatali, L., Amadori, D., Haffty, B. G., Sinha, S., Kang, Y.: Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2 [PMID 23086238] Nat Cell Biol 14(11): 1212-22, 2012.

Chakrabarti, R., Wei, Y., Hwang, J., Hang, X., Andres Blanco, M., Choudhury, A., Tiede, B., Romano, R. A., DeCoste, C., Mercatali, L., Ibrahim, T., Amadori, D., Kannan, N., Eaves, C. J., Sinha, S., Kang, Y.: DeltaNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling [PMID 25241036 ] Nat Cell Biol 16(10): 1004-15, 1-13, 2014.

Korpal, M., Ell, B. J., Buffa, F. M., Ibrahim, T., Blanco, M. A., Celia-Terrassa, T., Mercatali, L., Khan, Z., Goodarzi, H., Hua, Y., Wei, Y., Hu, G., Garcia, B. A., Ragoussis, J., Amadori, D., Harris, A. L., Kang, Y.: Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization [PMID 21822286] Nat Med 17(9): 1101-8, 2011.

Luo, G. Z., Blanco, M. A., Greer, E. L., He, C., Shi, Y.: DNA N(6)-methyladenine: a new epigenetic mark in eukaryotes? [PMID 26507168] Nat Rev Mol Cell Biol 16(12): 705-10, 2015.

Cheloufi, S., Elling, U., Hopfgartner, B., Jung, Y. L., Murn, J., Ninova, M., Hubmann, M., Badeaux, A. I., Euong Ang, C., Tenen, D., Wesche, D. J., Abazova, N., Hogue, M., Tasdemir, N., Brumbaugh, J., Rathert, P., Jude, J., Ferrari, F., Blanco, A., Fellner, M., Wenzel, D., Zinner, M., Vidal, S. E., Bell, O., Stadtfeld, M., Chang, H. Y., Almouzni, G., Lowe, S. W., Rinn, J., Wernig, M., Aravin, A., Shi, Y., Park, P. J., Penninger, J. M., Zuber, J., Hochedlinger, K.: The histone chaperone CAF-1 safeguards somatic cell identity [PMID 26659182] Nature 528(7581): 218-24, 2015.

Kumar Sushil, Wilkes David W, Samuel Nina, Blanco Mario Andres, Nayak Anupma, Alicea-Torres Kevin, Gluck Christian, Sinha Satrajit, Gabrilovich Dmitry, Chakrabarti Rumela: DeltaNp63-driven recruitment of myeloid-derived suppressor cells promotes metastasis in triple-negative breast cancer. [PMID 30295647] The Journal of clinical investigation 128(11): 5095-5109, Nov 2018.