Research Interests

Our overall goal is to understand the cell and molecular basis of germline cell differentiation and epigenetic reprogramming. My laboratory uses CRISPR/Cas9 gene editing technologies, next generation sequencing, pluripotent stem cells and mouse modeling to achieve this goal. Results from our work will provide a biological understanding of the cell and molecular basis of human life and child health, and potentially the foundation for a cell based therapy to overcome human infertility.

Selected Publications

Guo, J., Sosa, E., Chitiashvili, T., Nie, X., Roja, ER., Oliver, E., DonnorConnect, Plath, K., Hotaling, JA, Stukenborg, J-B., Clark, AT., Cairns, B (2021) Single-cell analysis of the developing human testis reveals somatic niche cell specification and fetal germline stem cell establishment. Cell Stem Cell. Published January 15.

Chitiashvili, T., Dror, I., Kim, R., Hsu, F-M., Chaudhari, R., Pandolfi, E., Chen, Di., Liebscher, S., Schenke-Layland, K., Plath, K., Clark A (2020) Female human primordial germ cells display X-chromosome dosage compensation despite the absence of X-inactivation. Nature Cell Biology. 22: 1436-1446

Liu, X., Ouyang, JF., Rossello, F., Tan, JP., Davidson, KC., Valdes, DS., Schroder, J., Sun, YBY., Chen, J., Knaupp, AS., Sun, G., Chy, HS., Huang, Z., Pflueger, J., Firas, J., Tano, V., Buckberry, S., Paynter, JM., Larcombe, MR., Poppe, D.,Choo, XY., O'Brien, CM., Pastor, WA., Chen, D., Leicher, AL., Naeem, H., Tripathi, P., Das, PP., Grubman, A., Powell, DR., Laslett, AL., David, L., Nilsson, SK., Clark, AT., Lister, R., Nfzger, CM., Martelotto, LG., Rackham, OJL., Polo, JM (2020) Reprogramming roadmap reveals route to human induced trophoblast stem cells. Nature 583: 101-107

Gell, J., Liu, W., Sosa, E., Chialastri, A., Hancock, G., Tao, Y., Wamaitha, SE., Bower, G, Day, S., Clark, AT (2020) An extended culture system that supports human primordial germ cell-like cell survival and initiation of DNA methylation erasure. Stem Cell Reports. 14:433-446

Chen, D., Sun, N., Hou, L., Kim, R., Faith, J., Aslanyan, M., Tao, Y., Zheng, Y., Fu, J., Liu, W., Kellis, M., Clark, AT. (2019). Human primordial germ cells are specified from lineage primed progenitors. Cell Reports 29: 4568-4582.e5

Clark, AT (2019). A Model of Human Embryo Implantation. Nature 573, 350-351 (2019)

Sosa, E., Chen, D., Rojas, EJ., Hennebold, JD., Peters, KA., Zhuang, Wu., Lam, TN., Mitchell, JM., Sukhwani, M., Tailor, RC., Meistrich, ML., Orwig, KE., Shetty, G., Clark, AT (2018) Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche. Nature Communications 9:5339

Gell, JJ and Clark, AT (2018) Restoring Fertility With Human Induced Pluripotent Stem Cells: Are We There Yet? Cell Stem Cell 23: 777-779

Pastor, WA., Liu, W., Chen, D., Ho, J., Kim, R., Hunt, T., Lukianchikov, A., Liu, X., Polo, JM., Jacobsen, SE., Clark, AT (2018) TFAP2C regulates transcription in human naive pluripotency by opening enhancers. Nature Cell Biology 20, 553-564

Chen, D., Clark, AT (2018). Mitochondiral DNA Selection in Human Germ Cells. Nature Cell Biology 20 118-120

Pastor W, Chen D, Liu W, Kim R, Sahakyan A, Lukianchikov A, Plath K, Jacobsen SE, Clark AT (2016). Naive human pluripotent stem cells feature a methylation landscape devoid of blastocyst or germline memory. Cell Stem Cell. 18: 1-7

Gkountela S, Zhang KX, Shafiq T, Liao W-W, Hargan-Calvopina J, P-Y Chen, Clark, AT (2015). DNA methylation dynamics in the human prenatal germline Cell. 161;1425-1436

Gkountela, S., Li, Z., Vincent, JJ, Zhang, KX, Chen, A., Pellegrini, M., Clark, AT (2013) The ontogeny of cKIT+ human primordial germ cells proves to be a resource for human germ line reprograming, imprint erasure and in vitro differentiation. Nature Cell Biology 15:113-122

Clark AT, Phillips BT, Orwig KE. Fruitful progress to fertility: male fertility in the test tube. Nature Medicine. 2011 Dec 6;17(12):1564-5

Chodavarapu RK., Feng, S., Bernatavichute, YV., Chen, PY., Stroud, H.,Yu, Y., Hetzel, JA., Kuo, F., Kim, J., Cokus, SJ., Casero, D., Bernal, M., Huijser, P., Clark, AT., Kra¨mer, U., Merchant, SS., Zhang, X., Jacobsem, SE., Pellegrini, M (2010) Relationship between nucleosome positioning and DNA methylation. Nature 466(7304):388-92

Xie, W., Song, C., Young, NL., Sperling, AS., Xu, F., Sridharan, R., Conway, AE., Garcia, BA., Plath, K., Clark, AT*., Grunstein, M*. (2009) Histone H3 lysine 56 acetylation is linked to the core transcriptional network in human embryonic stem cells. Molecular Cell. 33: 417-427 (* co-corresponding author)

Lowry, WE., Richter, L,. Yachechko, R., Pyle, AD., Tshieu, J., Sridharan, R., Clark, AT., Plath, K (2008) Generation of human induced pluripotent stem cells from dermal fibroblasts, PNAS Feb 26, 105(8):2883-2888

Bostick, M., Kim, JK., Esteve, PO, Clark, AT, Pradhan, S and Jacobson, SE (2007) UHRF1 plays a role in maintaining DNA methylation in mammalian cells Science (2007) 317:1760-1764