Karl Willert

TitleAssociate Professor In Residence
InstitutionUniversity of California San Diego
DepartmentCellular and Molecular Medicine
Address9500 Gilman Drive #0695
La Jolla CA 92093
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    Dr. Karl Willert is an expert in stem cell and developmental biology. Dr. Willert obtained a Bachelor of Science in Biochemistry from the University of California, San Diego (1989) and earned a Ph.D. in Biochemistry (1996) from the University of California, San Francisco under the guidance of Dr. Harold Varmus. Subsequently, he worked as a post-doctoral fellow with Dr. Roeland Nusse at Stanford University in Palo Alto, California. In 2008, after working in the biotechnology sector for a few years, Dr. Willert was recruited as an Assistant Professor in the Department of Cellular & Molecular Medicine at the University of California, San Diego.

    Underlying Dr. Willert’s research interests has been the study of WNT proteins, a family of secreted growth factors that regulate embryonic development and tissue homeostasis and impact a large number of human diseases, including neurodegeneration and cancer. Throughout his scientific career, Dr. Willert has incorporated biochemical, genetic and cell biological approaches to study these proteins and their signaling cascades. In a seminal study, Dr. Willert purified WNT proteins (he holds the patent on the “Composition of Active WNT protein”) and demonstrated that they harbor potent stem cell growth factor activities. His current research focuses on how WNT proteins regulate self renewal and differentiation of human pluripotent stem cells. He is actively collaborating on multiple projects, including with colleagues Dr. Dennis Carson (WNT-FZD signaling in cancer), Dr. Terry Gaasterland (genome-wide approaches to understanding WNT signaling), Dr. Maike Sander (generation of human pancreatic beta cells), Dr. David Traver (specification of hematopoietic stem cells), and Dr. Gene Yeo (integration of WNT signaling and RNA binding proteins).

    Dr. Willert has authored over 40 peer-reviewed publications, invited book chapters and review articles in the areas of WNT biochemistry and signaling and stem cell biology. Dr. Willert has been awarded 3 grants from the California Institute of Regenerative Medicine totaling $7.1 million. His research is also supported by The National Institute of Health and the National Foundation for Ectodermal Dysplasias.

    Research Focus Areas:

  • Developmental Biology

  • Signal Transduction

  • Stem Cell Biology

  • Collapse Research 
    Collapse Research Activities and Funding
    Incucyte Zoom Live Cell Analysis System
    NIH S10OD025060Apr 3, 2018 - Apr 2, 2019
    Role: Principal Investigator
    Wnt signaling in hematopoietic development
    NIH/NHLBI R01HL135205Jan 1, 2017 - Dec 31, 2020
    Role: Principal Investigator
    Analyzing the role of Wnt signaling during reprogramming.
    NIH/NIGMS R01GM110304Apr 10, 2014 - Feb 28, 2019
    Role: Principal Investigator
    Wnt Signaling in Development and Disease
    NIH/NCI R13CA128448Jun 1, 2007 - May 31, 2008
    Role: Principal Investigator

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    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Grainger S, Willert K. Mechanisms of Wnt signaling and control. Wiley Interdiscip Rev Syst Biol Med. 2018 Mar 30; e1422. PMID: 29600540.
      View in: PubMed
    2. Richter J, Stanley EG, Ng ES, Elefanty AG, Traver D, Willert K. WNT9A Is a Conserved Regulator of Hematopoietic Stem and Progenitor Cell Development. Genes (Basel). 2018 Jan 29; 9(2). PMID: 29382179.
      View in: PubMed
    3. Grainger S, Traver D, Willert K. Wnt Signaling in Hematological Malignancies. Prog Mol Biol Transl Sci. 2018 Jan; 153:321-341. PMID: 29389522.
      View in: PubMed
    4. Huggins IJ, Bos T, Gaylord O, Jessen C, Lonquich B, Puranen A, Richter J, Rossdam C, Brafman D, Gaasterland T, Willert K. The WNT target SP5 negatively regulates WNT transcriptional programs in human pluripotent stem cells. Nat Commun. 2017 10 18; 8(1):1034. PMID: 29044119.
      View in: PubMed
    5. Brafman D, Willert K. Wnt/ß-catenin signaling during early vertebrate neural development. Dev Neurobiol. 2017 Nov; 77(11):1239-1259. PMID: 28799266.
      View in: PubMed
    6. Rodvold JJ, Chiu KT, Hiramatsu N, Nussbacher JK, Galimberti V, Mahadevan NR, Willert K, Lin JH, Zanetti M. Intercellular transmission of the unfolded protein response promotes survival and drug resistance in cancer cells. Sci Signal. 2017 Jun 06; 10(482). PMID: 28588081.
      View in: PubMed
    7. Richter J, Traver D, Willert K. The role of Wnt signaling in hematopoietic stem cell development. Crit Rev Biochem Mol Biol. 2017 Aug; 52(4):414-424. PMID: 28508727.
      View in: PubMed
    8. Minegishi K, Hashimoto M, Ajima R, Takaoka K, Shinohara K, Ikawa Y, Nishimura H, McMahon AP, Willert K, Okada Y, Sasaki H, Shi D, Fujimori T, Ohtsuka T, Igarashi Y, Yamaguchi TP, Shimono A, Shiratori H, Hamada H. A Wnt5 Activity Asymmetry and Intercellular Signaling via PCP Proteins Polarize Node Cells for Left-Right Symmetry Breaking. Dev Cell. 2017 03 13; 40(5):439-452.e4. PMID: 28292423.
      View in: PubMed
    9. Grainger S, Lonquich B, Oon CH, Nguyen N, Willert K, Traver D. CRISPR Guide RNA Validation In Vitro. Zebrafish. 2017 08; 14(4):383-386. PMID: 27829120.
      View in: PubMed
    10. Grainger S, Richter J, Palazón RE, Pouget C, Lonquich B, Wirth S, Grassme KS, Herzog W, Swift MR, Weinstein BM, Traver D, Willert K. Wnt9a Is Required for the Aortic Amplification of Nascent Hematopoietic Stem Cells. Cell Rep. 2016 11 01; 17(6):1595-1606. PMID: 27806298.
      View in: PubMed
    11. Wang Z, Li B, Zhou L, Yu S, Su Z, Song J, Sun Q, Sha O, Wang X, Jiang W, Willert K, Wei L, Carson DA, Lu D. Prodigiosin inhibits Wnt/ß-catenin signaling and exerts anticancer activity in breast cancer cells. Proc Natl Acad Sci U S A. 2016 11 15; 113(46):13150-13155. PMID: 27799526.
      View in: PubMed
    12. Huggins IJ, Brafman D, Willert K. Methods to Manipulate and Monitor Wnt Signaling in Human Pluripotent Stem Cells. Methods Mol Biol. 2016; 1481:161-81. PMID: 27590161.
      View in: PubMed
    13. Kumar N, Richter J, Cutts J, Bush KT, Trujillo C, Nigam SK, Gaasterland T, Brafman D, Willert K. Generation of an expandable intermediate mesoderm restricted progenitor cell line from human pluripotent stem cells. Elife. 2015 Nov 10; 4. PMID: 26554899; PMCID: PMC4631902.
    14. Aznar N, Midde KK, Dunkel Y, Lopez-Sanchez I, Pavlova Y, Marivin A, Barbazán J, Murray F, Nitsche U, Janssen KP, Willert K, Goel A, Abal M, Garcia-Marcos M, Ghosh P. Daple is a novel non-receptor GEF required for trimeric G protein activation in Wnt signaling. Elife. 2015 Jun 30; 4:e07091. PMID: 26126266; PMCID: PMC4484057.
    15. Ross J, Busch J, Mintz E, Ng D, Stanley A, Brafman D, Sutton VR, Van den Veyver I, Willert K. A rare human syndrome provides genetic evidence that WNT signaling is required for reprogramming of fibroblasts to induced pluripotent stem cells. Cell Rep. 2014 Dec 11; 9(5):1770-1780. PMID: 25464842.
      View in: PubMed
    16. Moya N, Cutts J, Gaasterland T, Willert K, Brafman DA. Endogenous WNT signaling regulates hPSC-derived neural progenitor cell heterogeneity and specifies their regional identity. Stem Cell Reports. 2014 Dec 09; 3(6):1015-28. PMID: 25458891; PMCID: PMC4264562.
    17. Fernandez A, Huggins IJ, Perna L, Brafman D, Lu D, Yao S, Gaasterland T, Carson DA, Willert K. The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells. Proc Natl Acad Sci U S A. 2014 Jan 28; 111(4):1409-14. PMID: 24474766; PMCID: PMC3910637.
    18. Bauer M, Bénard J, Gaasterland T, Willert K, Cappellen D. WNT5A encodes two isoforms with distinct functions in cancers. PLoS One. 2013; 8(11):e80526. PMID: 24260410; PMCID: PMC3832467.
    19. Brafman DA, Moya N, Allen-Soltero S, Fellner T, Robinson M, McMillen ZL, Gaasterland T, Willert K. Analysis of SOX2-expressing cell populations derived from human pluripotent stem cells. Stem Cell Reports. 2013; 1(5):464-78. PMID: 24286033; PMCID: PMC3841266.
    20. Green JL, Bauer M, Yum KW, Li YC, Cox ML, Willert K, Wahl GM. Use of a molecular genetic platform technology to produce human Wnt proteins reveals distinct local and distal signaling abilities. PLoS One. 2013; 8(3):e58395. PMID: 23516471; PMCID: PMC3596392.
    21. Willert K, Nusse R. Wnt proteins. Cold Spring Harb Perspect Biol. 2012 Sep 01; 4(9):a007864. PMID: 22952392; PMCID: PMC3428774.
    22. Brafman DA, Chien S, Willert K. Arrayed cellular microenvironments for identifying culture and differentiation conditions for stem, primary and rare cell populations. Nat Protoc. 2012 Mar 15; 7(4):703-17. PMID: 22422316.
      View in: PubMed
    23. Gallegos TF, Kouznetsova V, Kudlicka K, Sweeney DE, Bush KT, Willert K, Farquhar MG, Nigam SK. A protein kinase A and Wnt-dependent network regulating an intermediate stage in epithelial tubulogenesis during kidney development. Dev Biol. 2012 Apr 01; 364(1):11-21. PMID: 22290330; PMCID: PMC3310225.
    24. Bauer M, Willert K. Wnt signaling: the ß-cat(enin)'s meow. Genes Dev. 2012 Jan 15; 26(2):105-9. PMID: 22279043; PMCID: PMC3273833.
    25. Mulligan KA, Fuerer C, Ching W, Fish M, Willert K, Nusse R. Secreted Wingless-interacting molecule (Swim) promotes long-range signaling by maintaining Wingless solubility. Proc Natl Acad Sci U S A. 2012 Jan 10; 109(2):370-7. PMID: 22203956; PMCID: PMC3258625.
    26. Brafman DA, Chang CW, Fernandez A, Willert K, Varghese S, Chien S. Long-term human pluripotent stem cell self-renewal on synthetic polymer surfaces. Biomaterials. 2010 Dec; 31(34):9135-44. PMID: 20817292; PMCID: PMC2949524.
    27. Hu T, Li C, Cao Z, Van Raay TJ, Smith JG, Willert K, Solnica-Krezel L, Coffey RJ. Myristoylated Naked2 antagonizes Wnt-beta-catenin activity by degrading Dishevelled-1 at the plasma membrane. J Biol Chem. 2010 Apr 30; 285(18):13561-8. PMID: 20177058; PMCID: PMC2859517.
    28. Lu D, Liu JX, Endo T, Zhou H, Yao S, Willert K, Schmidt-Wolf IG, Kipps TJ, Carson DA. Ethacrynic acid exhibits selective toxicity to chronic lymphocytic leukemia cells by inhibition of the Wnt/beta-catenin pathway. PLoS One. 2009 Dec 14; 4(12):e8294. PMID: 20011538; PMCID: PMC2789382.
    29. Brafman DA, Shah KD, Fellner T, Chien S, Willert K. Defining long-term maintenance conditions of human embryonic stem cells with arrayed cellular microenvironment technology. Stem Cells Dev. 2009 Oct; 18(8):1141-54. PMID: 19327010.
      View in: PubMed
    30. Lancaster MA, Louie CM, Silhavy JL, Sintasath L, Decambre M, Nigam SK, Willert K, Gleeson JG. Impaired Wnt-beta-catenin signaling disrupts adult renal homeostasis and leads to cystic kidney ciliopathy. Nat Med. 2009 Sep; 15(9):1046-54. PMID: 19718039; PMCID: PMC2895985.
    31. Brafman DA, de Minicis S, Seki E, Shah KD, Teng D, Brenner D, Willert K, Chien S. Investigating the role of the extracellular environment in modulating hepatic stellate cell biology with arrayed combinatorial microenvironments. Integr Biol (Camb). 2009 Sep; 1(8-9):513-24. PMID: 20023766.
      View in: PubMed
    32. Eguchi A, Meade BR, Chang YC, Fredrickson CT, Willert K, Puri N, Dowdy SF. Efficient siRNA delivery into primary cells by a peptide transduction domain-dsRNA binding domain fusion protein. Nat Biotechnol. 2009 Jun; 27(6):567-71. PMID: 19448630; PMCID: PMC2694965.
    33. Soda M, Willert K, Kaushansky K, Geddis AE. Inhibition of GSK-3beta promotes survival and proliferation of megakaryocytic cells through a beta-catenin-independent pathway. Cell Signal. 2008 Dec; 20(12):2317-23. PMID: 18804163; PMCID: PMC2677808.
    34. Willert KH. Isolation and application of bioactive Wnt proteins. Methods Mol Biol. 2008; 468:17-29. PMID: 19099243.
      View in: PubMed
    35. Willert K, Jones KA. Wnt signaling: is the party in the nucleus? Genes Dev. 2006 Jun 01; 20(11):1394-404. PMID: 16751178.
      View in: PubMed
    36. Galli LM, Barnes T, Cheng T, Acosta L, Anglade A, Willert K, Nusse R, Burrus LW. Differential inhibition of Wnt-3a by Sfrp-1, Sfrp-2, and Sfrp-3. Dev Dyn. 2006 Mar; 235(3):681-90. PMID: 16425220; PMCID: PMC2566934.
    37. Duncan AW, Rattis FM, DiMascio LN, Congdon KL, Pazianos G, Zhao C, Yoon K, Cook JM, Willert K, Gaiano N, Reya T. Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol. 2005 Mar; 6(3):314-22. PMID: 15665828.
      View in: PubMed
    38. Galli LM, Willert K, Nusse R, Yablonka-Reuveni Z, Nohno T, Denetclaw W, Burrus LW. A proliferative role for Wnt-3a in chick somites. Dev Biol. 2004 May 15; 269(2):489-504. PMID: 15110715.
      View in: PubMed
    39. Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, Yates JR, Nusse R. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature. 2003 May 22; 423(6938):448-52. PMID: 12717451.
      View in: PubMed
    40. Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, Hintz L, Nusse R, Weissman IL. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003 May 22; 423(6938):409-14. PMID: 12717450.
      View in: PubMed