Education
BA – Williams College, Williamstown, Massachusetts
PhD – University of Washington, Seattle
Postdoctoral Fellowship – University of Washington, Seattle
Postdoctoral Fellowship – University of California at San Diego, La Jolla
Research Interests
- Embryonic specification of hematopoietic stem cells
- Integrated development of the vascular and hematopoietic systems
- Molecular basis of leukemia
Our major goal is to understand the cellular and molecular environment that directs specification of the earliest hematopoietic stem cells (HSCs) from primitive endothelium in the dorsal aorta. Our previous work indicated that migratory cells formed a transient local environment that was likely critical to supply necessary inductive signals, a “specification niche” (Clements et al., Nature 2011). More recently, we have identified two key populations of cells that contribute to the specification niche, one deriving from neural crest (Damm and Clements, Nature Cell Biol, 2017), and one deriving from the primitive somite (in progress). Our future studies will build on these observations to identify the specific molecular factors that specify HSCs and elaborate the niche architecture. These studies will inform long-term efforts to produce HSCs in vitro for regenerative medicine, transplantation, and as a platform for delivery of gene therapy.
In complementary work, we are working to establish zebrafish models of B lineage leukemia as a paradigm for functionally investigating the significance of putative oncogenes and tumor suppressor mutations. Development and cancer are conceptually related biological processes; desirable cell behaviors during development—such as cell proliferation and migration—are frequently aberrantly reawakened in malignancy. We are interested in how normal hematopoietic programs are coopted by genetic alterations to influence tumor formation, metastasis, therapy success, relapse potential, and other critical aspects of cancer biology related to treatment.
Selected Publications
Damm EW, Clements WK. Pdgf signalling guides neural crest contribution to the haematopoietic stem cell specification niche. Nature Cell Biology 19:457-467, 2017.
Genthe JR, Clements WK. R-spondin-1 is required for specification of hematopoietic stem cells through Wnt16 and Vegfa signaling pathways. Development 144:590-600, 2017.
Butko E, Distel M, Pouget C, Weijts B, Kobayashi I, Ng K, Mosimann C, Poulain FE, McPherson A, Ni C-W, Stachura DL, Del Cid N, Lawson ND, Dorsky R, Clements WK, Traver D. Gata2b is an early marker of hemogenic endothelium and is required for hematopoietic stem cell emergence. Development 142:1050-61, 2015.
Lee Y, Manegold JE, Kim AD, Pouget C, Stachura DL, Clements WK, Traver D. FGF signaling specifies hematopoietic stem cells through its regulation of somitic Notch signaling. Nat Commun 5:5583, 2014. 10:doi:10.1038/ncomms6583
Kim AD, Melick C, Clements WK, Stachura DL, Distel M, Traver D. Discrete Notch signaling requirements in the specification of hematopoietic stem cells. EMBO J 33:2363-2373, 2014.
Clements WK, Traver D. Signalling pathways that control vertebrate haematopoietic stem cell specification. Nature Rev Immunol 13:336-348, 2013.
Clements WK, Traver D. Fish Pharming: Zebrafish Anti-Leukemia Screening. Blood 119:5614-5, 2012.
Clements WK, Kim AD, Ong KG, Moore JC, Lawson ND, Traver D. A somitic Wnt16/Notch pathway specifies haematopoietic stem cells. Nature 474:220-224, 2011.
Clements WK, Ong KG, Traver D. Zebrafish wnt3 is expressed in developing neural tissue. Dev Dyn 238:1788-95, 2009.
Clements WK, Kimelman D. “Analysis of Wnt Signaling in Xenopus Embryos” in Analysis of Growth Factor Signaling in Embryos. Whitman, M. and Sater, A.K., eds. Taylor & Francis Group, LLC, Boca Raton, FL:1-27, 2006.
Clements WK, Kimelman D. LZIC regulates neuronal survival during zebrafish development. Dev Biol 283:322-334, 2005.
Xing Y, Clements WK, Trong IL, Hinds TR, Stenkamp R, Kimelman D, Xu W. Crystal structure of a Beta-catenin/APC complex reveals a critical role for APC phosphorylation in APC function. Mol Cell 15:523-533, 2004.
Xing Y, Clements WK, Kimelman D, Xu W. Crystal structure of a Beta-catenin/Axin complex suggests a mechanism for the Beta-catenin destruction complex. Genes & Dev 17:2753-2764, 2003.
Clements WK, Kimelman D. Wnt Signaling Gets Xeeky. Nat Cell Biol 5:861-863, 2003.
Graham TA, Clements WK, Kimelman D, Xu W. The crystal structure of the Beta-catenin/ICAT complex reveals the inhibitory mechanism of ICAT. Mol Cell 10:563-571, 2002.
Melby AE, Clements WK, Kimelman D. Regulation of dorsal gene expression in Xenopus by the ventralizing homeodomain gene Vox Dev Biol 15:293-305, 1999.
Last update: April 2017