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M. ANDRES BLANCO, PhD, BA

Assistant Professor, Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine

Research Areas: We study the mechanisms by which epigenetic information is encoded, interpreted, and propagated in normal and pathological (eg. cancerous) cell identity programs.
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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

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 Cell 161: 868-78, 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 Nature 528: 218-24, 2015.

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 Cancer Cell 26: 92-105, 2014.

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 Nat Cell Biol 16: 1004-15, 1-13, 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 Cell 157: 869-81, 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 Cancer Cell 26: 358-373, 2014.

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 Epigenetics Chromatin 6: 20, 2013.

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 Cell Res 22: 1339-55, 2012.

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 Nat Cell Biol 14: 1212-22, 2012.

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 Genome Biol 13: R68, 2012.

PhD (Molecular Biology) Princeton University, 2011

BA (Biological Sciences, Philosophy) Cornell University, 2004