Professor Hans-Willem Snoeck Phone: 212-342-0182 Lab Phone: 212-305-2459 Fax: 212-305-1468 Email: hs2680@columbia.edu

Professor Hans-Willem Snoeck
Phone: 212-342-0182
Lab Phone: 212-305-2459
Fax: 212-305-1468
Email: hs2680@columbia.edu

Hans-Willem Snoeck, M.D., Ph.D.

Byron M. Thomashow Professor of Medicine (in Microbiology & Immunology)
M.D., Ph.D., University of Antwerp, Belgium

Hematopoietic stem cell biology

Research
The research program of the Snoeck lab primarily focuses on hematopoiesis with the aim to improve bone marrow transplantation and gene therapy targeted at hematopoietic stem cells (HSCs), and gain insight in leukemogenesis. To achieve a deeper understanding of the mechanisms involved in self-renewal of HSCs, we have mapped genes underlying quantitative genetic variation in the behavior of HSCs among inbred mouse strains. After identifying allelic variation in the Prdm16 gene as one of the underlying mechanisms, the lab now focuses on the mechanism of action of Prdm16 in the renewal of HSCs. Expansion of this program into directed differentiation of human embryonic stem cells (ESCs) and induced pluripotent state cells (iPSCs) (collectively called human pluritpotent cells (hPSCs)) arose from the desire to attempt to alleviate post-bone marrow transplantation immune deficiency, caused, among others, by defective T cell reconstitution. Furthermore, the capacity to generate thymic epithelial cells from human pluripotent stem cells will allow the generation of the next generation of "personal immune" mice. As the thymus develops from the anterior foregut endoderm, the approaches we developed also led to strategies to generate virtually every type of cell of the respiratory system from hPSCs.

 

Selected Publications

  1. Matkovic Leko, I., Schneider, R.T., Thimraj, T.A., Schrode, N., Beitler, D., Liu, H.Y., Beaumont, K., Chen, Y.W. and Snoeck, H.W. (2023) A distal lung organoid model to study interstitial lung disease, viral infection and human lung development. Nature Protoc. 18: 2283–2312. https://doi.org/10.1038/s41596-023-00827-6

  2. Rodrigues Toste de Carvalho, A.L., Liu, H.Y., Chen, Y.W., Porotto, M., Moscona, A. and Snoeck, H.W. (2021) The in vitro multilineage differentiation and maturation of lung and airway cells from human pluripotent stem cell-derived lung progenitors in 3D. Nature Protoc. 16: 1802–1829. https://doi.org/10.1038/s41596-020-00476-z

  3. Fidler, T.P., Xue, C., Yalcinkaya, M., Hardaway, B., Abramowicz, S., Xiao, T., Liu, W., Thomas, D.G., Hajebrahimi, M.A., Pircher, J., Silvestre-Roig, C., Kotini, A.G., Luchsinger, L.L., Wei, Y., Westerterp, M., Snoeck, H.W., Papapetrou, E.P., Schulz, C., Massberg, S., Soehnlein, O., Ebert, B., Levine, R.L., Reilly, M.P., Libby, P., Wang, N. and Tall, A.R. (2021) The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis. Nature 592: 296–301. https://doi.org/10.1038/s41586-021-03341-5

  4. Snoeck H.W. (2020). Calcium regulation of stem cells. EMBO Reports 21: e50028. https://doi.org/10.15252/embr.202050028

  5. Strikoudis, A., Cieślak, A., Loffredo, L., Chen, Y.W., Patel, N., Saqi, A., Lederer, D.J. and Snoeck, H.W. (2019) Modeling of fibrotic lung disease using 3D organoids derived from human pluripotent stem cells. Cell Reports 27: 3709–3723.e5. https://doi.org/10.1016/j.celrep.2019.05.077

  6. Luchsinger, L.L., Strikoudis, A., Danzl, N.M., Bush, E.C., Finlayson, M.O., Satwani, P., Sykes, M., Yazawa, M. and Snoeck, H.W. (2019) Harnessing hematopoietic stem cell low intracellular calcium improves their maintenance in vitro. Cell Stem Cell 25: 225–240.e7. https://doi.org/10.1016/j.stem.2019.05.002

  7. Porotto, M., Ferren, M., Chen, Y.W., Siu, Y., Makhsous, N., Rima, B., Briese, T., Greninger, A.L., Snoeck, H.W. and Moscona, A. (2019) Authentic modeling of human respiratory virus infection in human pluripotent stem cell-derived lung organoids. mBio 10: e00723-19. https://doi.org/10.1128/mBio.00723-19

  8. Zhang, Y., Yang, Y., Jiang, M., Huang, S.X., Zhang, W., Al Alam, D., Danopoulos, S., Mori, M., Chen, Y.W., Balasubramanian, R., Chuva de Sousa Lopes, S.M., Serra, C., Bialecka, M., Kim, E., Lin, S., Toste de Carvalho, A.L.R., Riccio, P.N., Cardoso, W.V., Zhang, X., Snoeck, H.W. and Que, J. (2018) 3D modeling of esophageal development using human PSC-derived basal progenitors reveals a critical role for Notch signaling. Cell Stem Cell 23: 516-529 e515.

  9. Corrigan, D.J., Luchsinger, L.L., Justino de Almeida, M., Williams, L.J., Strikoudis, A. and Snoeck, H.W. (2018) PRDM16 isoforms differentially regulate normal and leukemic hematopoiesis and inflammatory gene signature. J. Clin. Invest. 128: 3250-3264.

  10. de Almeida, M.J., Luchsinger, L.L., Corrigan, D.J., Williams, L.J. and Snoeck, H.W. (2017) Dye-independent methods reveal elevated mitochondrial mass in hematopoietic stem cells. Cell Stem Cell 21: 725-729: e724.

  11. Chen, Y.W., Huang, S.X., de Carvalho, A., Ho, S.H., Islam, M.N., Volpi, S., Notarangelo, L.D., Ciancanelli, M., Casanova, J.L., Bhattacharya, J., Liang, A.F., Palermo, L.M., Porotto, M., Moscona, A. and Snoeck, H.W. (2017) A three-dimensional model of human lung development and disease from pluripotent stem cells. Nature Cell Biol. 19: 542-549.

  12. Adams, W.C., Chen, Y.H., Kratchmarov, R., Yen, B., Nish, S.A., Lin, W.W., Rothman, N.J., Luchsinger, L.L., Klein, U., Busslinger, M., Rathmell, J.C., Snoeck, H.W. and Reiner, S.L. (2016) Anabolism-associated mitochondrial stasis driving lymphocyte differentiation over self-renewal. Cell Rep. 17: 3142-3152.

  13. Luchsinger, L.L., de Almeida, M.J., Corrigan, D.J., Mumau, M. and Snoeck, H.W. (2016) Mitofusin 2 maintains haematopoietic stem cells with extensive lymphoid potential. Nature529: 528-531.

  14. Snoeck, H.W. (2015) Progenitor cell engraftment in the lung: at last? Nature Med. 21: 842-844.

  15. Snoeck, H.W. (2015) Can metabolic mechanisms of stem cell maintenance explain aging and the immortal germline? Cell Stem Cell 16: 582-584.

  16. Ciancanelli, M.J., Huang, S.X., Luthra, P., Garner, H., Itan, Y., Volpi, S., Lafaille, F.G., Trouillet, C., Schmolke, M., Albrecht, R.A., Israelsson, E., Lim, H.K., Casadio, M., Hermesh, T., Lorenzo, L., Leung, L.W., Pedergnana, V., Boisson, B., Okada, S., Picard, C., Ringuier, B., Troussier, F., Chaussabel, D., Abel, L., Pellier, I., Notarangelo, L.D., Garcia-Sastre, A., Basler, C.F., Geissmann, F., Zhang, S.Y., Snoeck, H.W. and Casanova, J.L. (2015) Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. Science348: 448-453.

  17. Huang, S.X., Green, M.D., de Carvalho, A.T., Mumau, M., Chen, Y.W., D'Souza, S.L. and Snoeck, H.W. (2015) The in vitro generation of lung and airway progenitor cells from human pluripotent stem cells. Nature Protoc. 10: 413-425.

  18. Snoeck, H.W. (2015) Modeling human lung development and disease using pluripotent stem cells. Development 142: 13-16.

  19. Huang, S.X., Islam, M.N., O'Neill, J., Hu, Z., Yang, Y.G., Chen, Y.W., Mumau, M., Green, M.D., Vunjak-Novakovic, G., Bhattacharya, J. and Snoeck, H.W. (2014) Efficient generation of lung and airway epithelial cells from human pluripotent stem cells. Nature Biotechnol. 32: 84-91.

  20. Baker, S.J., Ma'ayan A, Lieu, Y.K., John, P., Reddy, M.V.R., Chen, E.Y., Duan, Q., Snoeck, H.W. and Reddy, E.P. (2014) B-myb is an essential regulator of hematopoietic stem cell and myeloid progenitor cell development. Proc. Natl. Acad. Sci. U.S.A. 111: 3122-3127.

  21. Kamezaki, K., Luchsinger, L.L. and Snoeck, H.W. (2014) Differential requirement for wild-type Flt3 in leukemia initiation among mouse models of human leukemia. Exp. Hematol. 42: 192-203 e191.

  22. Green, M.D., Huang, S.X. and Snoeck, H.W. (2013). Stem cells of the respiratory system: From identification to differentiation into functional epithelium. Bioessays 35: 261-270. PMID: 23175215.

  23. Snoeck, H.W. (2013) Aging of the hematopoietic system. Curr. Opin. Hematol. 20: 355-361.

  24. Longmire, T.A., Ikonomou, L., Hawkins, F., Christodoulou, C., Cao, Y., Jean, J.C., Kwok, L.W., Mou, H., Rajagopal, J., Shen, S.S., Dowton, A.A., Serra, M., Weiss, D.J., Green, M.D., Snoeck, H.W., Ramirez, M.I. and Kotton, D.N. (2012) Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells. Cell Stem Cell 10: 398-411. PMCID: PMC3322392.

  25. Green, M.D., Chen, A., Nostro, M.C., d'Souza, S.L., Schaniel, C., Lemischka, I.R., Gouon-Evans, V., Keller, G. and Snoeck, H.W. (2011). Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells. Nature Biotechnol. 29: 267-72. PMID: 21358635.

  26. Aguilo F, Avagyan S, Labar A, Sevilla A, Lee DF, Kumar P, Lemischka IR, Zhou BY and Snoeck HW. (2011). Prdm16 is a physiologic regulator of hematopoietic stem cells. Blood 117: 5057-66. PMCID: PMC3109532.

  27. Avagyan, S., Aguilo, F., Kamezaki, K. and Snoeck, H.W. (2011) Quantitative trait mapping reveals a regulatory axis involving peroxisome proliferator-activated receptors, PRDM16, transforming growth factor-beta2 and FLT3 in hematopoiesis. Blood 118: 6078-6086.

  28. Kumar, R., Avagyan, S. and Snoeck, H.W. (2010). A quantitative trait locus on chr.4 regulates thymic involution. J. Gerontol. A. Biol. Sci. Med. Sci. 65: 620-5. PMCID: PMC2904592.

  29. Yvan-Charvet, L., Pagler, T., Gautier, E.L., Avagyan, S., Siry, R.L., Han, S., Welch, C.L., Wang, N., Randolph, G.J., Snoeck, H.W. and Tall, A.R. (2010). ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation. Science 328: 1689-93. PMCID: PMC3032591.

  30. Fossati, V., Kumar, R. and Snoeck, H.W. (2010). Progenitor cell origin plays a role in fate choices of mature B cells. J. Immunol. 184: 1251-60. PMCID: PMC2809811.