The Wnt pathway is an evolutionarily conserved signaling pathway present in all metazoans. During development, Wnt signaling coordinate the formation of tissues, organs, and limbs, and its misregulation leads to a variety of human disease states such Alzheimeri's disease and cancer. My laboratory is interested in understanding the basic mechanism by which a Wnt signal is propagated and how this information can be used in regenerative medicine and in the treatment of cancer.

A major experimental approach in my laboratory involves the use of Xenopus extracts and purified proteins to biochemically reconstitute Wnt signaling in vitro. Genome-scale screens, cultured mammalian cells, Xenopus embryos, Drosophila genetics (in collaboration with Dr. Laura Lee), and mouse studies are employed to compliment and extend our biochemical findings.

One of the major mysteries of this pathway is how a Wnt signal is propagated from the cell surface. My laboratory has recently developed an in vitro system to study the mechanism of Wnt signal transduction from the plasma membrane. Towards this end, we have focused on understanding the mechanism of signaling from the coreceptor, LRP6, and the potential role of the membrane associated heterotrimeric G protein family members in Wnt signal transduction. Many components of the Wnt pathway are regulated by ubiquitin-mediated proteolysis. Recently, we have taken a genome-scale screen to identify deubiquitinating enzyme (DUBs) and ubiquitin ligases (E3s) that regulate the Wnt pathway. Several hits have been identified from these screens, and current efforts are directed towards validating their roles in Wnt signaling.

In regenerative medicine, the healing process is manipulated to repair damaged tissues. Modern regenerative medicine is a field in which stem cells are manipulated to treat a variety of human diseases. Wnt signaling is one of a handful of molecular pathways critical to stem cells. Thus, agents that target Wnt signaling would be potentially useful for the treatment of cardiovascular disease, diabetes, neurodegeneration, and other disorders that may benefit from regenerative medicine.

Cancer stem cells (CSC) are fundamental to the initiation and maintenance of tumors. Failure to eradicate CSC (as is typical with conventional therapy) leaves behind a small reservoir of cells that drives relapse. Wnt inhibitors would be expected to specifically target this resistant CSC population. Using our Xenopus biochemical system, we have found several compounds that potently inhibit the Wnt pathway. One of these, VU-WS30, inhibits the viability of a variety of cancer cell lines that are highly dependent on Wnt signaling for growth and proliferation. Current efforts are directed towards identifying the molecular targets of VU-WS30 and other Wnt inhibitors identified in our screen.


The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. The Casein kinase 1α agonist pyrvinium attenuates Wnt-mediated CK1α degradation via interaction with the E3 ubiquitin ligase component Cereblon. Shen C, Nayak A, Neitzel LR, Yang F, Li B, Williams CH, Hong CC, Ahmed Y, Lee E, Robbins DJ (2022) J Biol Chem 298(8): 102227
    › Primary publication · 35780831 (PubMed)
  2. Utilizing Three-Dimensional Culture Methods to Improve High-Throughput Drug Screening in Anaplastic Thyroid Carcinoma. Bergdorf K, Bauer JA, Westover D, Phifer C, Murphy B, Tyson DR, Lee E, Weiss VL (2022) Cancers (Basel) 14(8)
    › Primary publication · 35454763 (PubMed) · PMC9031362 (PubMed Central)
  3. DDR1 contributes to kidney inflammation and fibrosis by promoting the phosphorylation of BCR and STAT3. Borza CM, Bolas G, Bock F, Zhang X, Akabogu FC, Zhang MZ, de Caestecker M, Yang M, Yang H, Lee E, Gewin L, Fogo AB, McDonald WH, Zent R, Pozzi A (2022) JCI Insight 7(3)
    › Primary publication · 34941574 (PubMed) · PMC8855801 (PubMed Central)
  4. The E3 ubiquitin ligase component, Cereblon, is an evolutionarily conserved regulator of Wnt signaling. Shen C, Nayak A, Neitzel LR, Adams AA, Silver-Isenstadt M, Sawyer LM, Benchabane H, Wang H, Bunnag N, Li B, Wynn DT, Yang F, Garcia-Contreras M, Williams CH, Dakshanamurthy S, Hong CC, Ayad NG, Capobianco AJ, Ahmed Y, Lee E, Robbins DJ (2021) Nat Commun 12(1): 5263
    › Primary publication · 34489457 (PubMed) · PMC8421366 (PubMed Central)
  5. Immunofluorescent staining of cancer spheroids and fine-needle aspiration-derived organoids. Bergdorf KN, Phifer CJ, Bechard ME, Lee MA, McDonald OG, Lee E, Weiss VL (2021) STAR Protoc 2(2): 100578
    › Primary publication · 34136836 (PubMed) · PMC8182106 (PubMed Central)
  6. Induction of Wnt signaling antagonists and p21-activated kinase enhances cardiomyocyte proliferation during zebrafish heart regeneration. Peng X, Lai KS, She P, Kang J, Wang T, Li G, Zhou Y, Sun J, Jin D, Xu X, Liao L, Liu J, Lee E, Poss KD, Zhong TP (2021) J Mol Cell Biol 13(1): 41-58
    › Primary publication · 33582796 (PubMed) · PMC8035995 (PubMed Central)
  7. Obtaining patient-derived cancer organoid cultures via fine-needle aspiration. Phifer CJ, Bergdorf KN, Bechard ME, Vilgelm A, Baregamian N, McDonald OG, Lee E, Weiss VL (2021) STAR Protoc 2(1): 100220
    › Primary publication · 33377121 (PubMed) · PMC7758553 (PubMed Central)
  8. High-throughput drug screening of fine-needle aspiration-derived cancer organoids. Bergdorf K, Phifer C, Bharti V, Westover D, Bauer J, Vilgelm A, Lee E, Weiss V (2020) STAR Protoc 1(3): 100212
    › Primary publication · 33377106 (PubMed) · PMC7757655 (PubMed Central)
  9. Casein Kinase 1α as a Regulator of Wnt-Driven Cancer. Shen C, Nayak A, Melendez RA, Wynn DT, Jackson J, Lee E, Ahmed Y, Robbins DJ (2020) Int J Mol Sci 21(16)
    › Primary publication · 32824859 (PubMed) · PMC7460588 (PubMed Central)
  10. Fine-Needle Aspiration-Based Patient-Derived Cancer Organoids. Vilgelm AE, Bergdorf K, Wolf M, Bharti V, Shattuck-Brandt R, Blevins A, Jones C, Phifer C, Lee M, Lowe C, Hongo R, Boyd K, Netterville J, Rohde S, Idrees K, Bauer JA, Westover D, Reinfeld B, Baregamian N, Richmond A, Rathmell WK, Lee E, McDonald OG, Weiss VL (2020) iScience 23(8): 101408
    › Primary publication · 32771978 (PubMed) · PMC7415927 (PubMed Central)
  11. Nuclear Regulation of Wnt/β-Catenin Signaling: It's a Complex Situation. Anthony CC, Robbins DJ, Ahmed Y, Lee E (2020) Genes (Basel) 11(8)
    › Primary publication · 32759724 (PubMed) · PMC7465203 (PubMed Central)
  12. Tubular β-catenin and FoxO3 interactions protect in chronic kidney disease. Nlandu-Khodo S, Osaki Y, Scarfe L, Yang H, Phillips-Mignemi M, Tonello J, Saito-Diaz K, Neelisetty S, Ivanova A, Huffstater T, McMahon R, Taketo MM, deCaestecker M, Kasinath B, Harris RC, Lee E, Gewin LS (2020) JCI Insight 5(10)
    › Primary publication · 32369448 (PubMed) · PMC7259539 (PubMed Central)
  13. Hyperoxia Injury in the Developing Lung Is Mediated by Mesenchymal Expression of Wnt5A. Sucre JMS, Vickers KC, Benjamin JT, Plosa EJ, Jetter CS, Cutrone A, Ransom M, Anderson Z, Sheng Q, Fensterheim BA, Ambalavanan N, Millis B, Lee E, Zijlstra A, Königshoff M, Blackwell TS, Guttentag SH (2020) Am J Respir Crit Care Med 201(10): 1249-1262
    › Primary publication · 32023086 (PubMed) · PMC7233334 (PubMed Central)
  14. The CK1α Activator Pyrvinium Enhances the Catalytic Efficiency (/) of CK1α. Shen C, Li B, Astudillo L, Deutscher MP, Cobb MH, Capobianco AJ, Lee E, Robbins DJ (2019) Biochemistry 58(51): 5102-5106
    › Primary publication · 31820934 (PubMed) · PMC6942998 (PubMed Central)
  15. Novel three-dimensional cultures provide insights into thyroid cancer behavior. Lee MA, Bergdorf KN, Phifer CJ, Jones CY, Byon SY, Sawyer LM, Bauer JA, Weiss VL (2020) Endocr Relat Cancer 27(2): 111-121
    › Primary publication · 31804972 (PubMed) · PMC7295136 (PubMed Central)
  16. Single-Cell Analyses Confirm the Critical Role of LRP6 for Wnt Signaling in APC-Deficient Cells. Cabel CR, Alizadeh E, Robbins DJ, Ahmed Y, Lee E, Thorne CA (2019) Dev Cell 49(6): 827-828
    › Primary publication · 31211991 (PubMed) · PMC6613640 (PubMed Central)
  17. Discovering small molecules as Wnt inhibitors that promote heart regeneration and injury repair. Xie S, Fu W, Yu G, Hu X, Lai KS, Peng X, Zhou Y, Zhu X, Christov P, Sawyer L, Ni TT, Sulikowski GA, Yang Z, Lee E, Zeng C, Wang WE, Zhong TP (2020) J Mol Cell Biol 12(1): 42-54
    › Primary publication · 30925593 (PubMed) · PMC7259332 (PubMed Central)
  18. Developmental regulation of Wnt signaling by Nagk and the UDP-GlcNAc salvage pathway. Neitzel LR, Spencer ZT, Nayak A, Cselenyi CS, Benchabane H, Youngblood CQ, Zouaoui A, Ng V, Stephens L, Hann T, Patton JG, Robbins D, Ahmed Y, Lee E (2019) Mech Dev : 20-31
    › Primary publication · 30904594 (PubMed) · PMC6574174 (PubMed Central)
  19. Blood vessel epicardial substance (BVES) reduces LRP6 receptor and cytoplasmic -catenin levels to modulate Wnt signaling and intestinal homeostasis. Thompson JJ, Short SP, Parang B, Brown RE, Li C, Ng VH, Saito-Diaz K, Choksi YA, Washington MK, Smith JJ, Fingleton B, Brand T, Lee E, Coffey RJ, Williams CS (2019) Carcinogenesis
    › Primary publication · 30689807 (PubMed) · PMC8067673 (PubMed Central)
  20. Characterization of a null allele in . Neitzel LR, Broadus MR, Zhang N, Sawyer L, Wallace HA, Merkle JA, Jodoin JN, Sitaram P, Crispi EE, Rork W, Lee LA, Pan D, Gould KL, Page-McCaw A, Lee E (2018) Biol Open 7(7)
    › Primary publication · 29945873 (PubMed) · PMC6078348 (PubMed Central)
  21. Phosphorylation of XIAP at threonine 180 controls its activity in Wnt signaling. Ng VH, Hang BI, Sawyer LM, Neitzel LR, Crispi EE, Rose KL, Popay TM, Zhong A, Lee LA, Tansey WP, Huppert S, Lee E (2018) J Cell Sci 131(10)
    › Primary publication · 29678905 (PubMed) · PMC6031333 (PubMed Central)
  22. APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway. Saito-Diaz K, Benchabane H, Tiwari A, Tian A, Li B, Thompson JJ, Hyde AS, Sawyer LM, Jodoin JN, Santos E, Lee LA, Coffey RJ, Beauchamp RD, Williams CS, Kenworthy AK, Robbins DJ, Ahmed Y, Lee E (2018) Dev Cell 44(5): 566-581.e8
    › Primary publication · 29533772 (PubMed) · PMC5884143 (PubMed Central)
  23. Chemical Screening Using Cell-Free Egg Extract. Broadus MR, Lee E (2018) Cold Spring Harb Protoc 2018(8)
    › Primary publication · 29475996 (PubMed) · PMC6368528 (PubMed Central)
  24. Casein kinase1α activators, a precision weapon for CRC. Li B, Lee E, Robbins DJ (2017) Oncotarget 8(57): 96462-96463
    › Primary publication · 29228537 (PubMed) · PMC5722489 (PubMed Central)
  25. lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/β-catenin signaling. Lu Y, Zhao X, Liu Q, Li C, Graves-Deal R, Cao Z, Singh B, Franklin JL, Wang J, Hu H, Wei T, Yang M, Yeatman TJ, Lee E, Saito-Diaz K, Hinger S, Patton JG, Chung CH, Emmrich S, Klusmann JH, Fan D, Coffey RJ (2017) Nat Med 23(11): 1331-1341
    › Primary publication · 29035371 (PubMed) · PMC5961502 (PubMed Central)
  26. Inhibition of WNT signaling attenuates self-renewal of SHH-subgroup medulloblastoma. Rodriguez-Blanco J, Pednekar L, Penas C, Li B, Martin V, Long J, Lee E, Weiss WA, Rodriguez C, Mehrdad N, Nguyen DM, Ayad NG, Rai P, Capobianco AJ, Robbins DJ (2017) Oncogene 36(45): 6306-6314
    › Primary publication · 28714964 (PubMed) · PMC5680121 (PubMed Central)
  27. Blocking TGF- and -Catenin Epithelial Crosstalk Exacerbates CKD. Nlandu-Khodo S, Neelisetty S, Phillips M, Manolopoulou M, Bhave G, May L, Clark PE, Yang H, Fogo AB, Harris RC, Taketo MM, Lee E, Gewin LS (2017) J Am Soc Nephrol 28(12): 3490-3503
    › Primary publication · 28701516 (PubMed) · PMC5698068 (PubMed Central)
  28. Pharmacologic Inhibition of β-Catenin With Pyrvinium Inhibits Murine and Human Models of Wilms Tumor. Polosukhina D, Love HD, Moses HL, Lee E, Zent R, Clark PE (2017) Oncol Res 25(9): 1653-1664
    › Primary publication · 28695795 (PubMed) · PMC5670010 (PubMed Central)
  29. Differential abundance of CK1α provides selectivity for pharmacological CK1α activators to target WNT-dependent tumors. Li B, Orton D, Neitzel LR, Astudillo L, Shen C, Long J, Chen X, Kirkbride KC, Doundoulakis T, Guerra ML, Zaias J, Fei DL, Rodriguez-Blanco J, Thorne C, Wang Z, Jin K, Nguyen DM, Sands LR, Marchetti F, Abreu MT, Cobb MH, Capobianco AJ, Lee E, Robbins DJ (2017) Sci Signal 10(485)
    › Primary publication · 28655862 (PubMed) · PMC5555225 (PubMed Central)
  30. Comparative genetic screens in human cells reveal new regulatory mechanisms in WNT signaling. Lebensohn AM, Dubey R, Neitzel LR, Tacchelly-Benites O, Yang E, Marceau CD, Davis EM, Patel BB, Bahrami-Nejad Z, Travaglini KJ, Ahmed Y, Lee E, Carette JE, Rohatgi R (2016) Elife
    › Primary publication · 27996937 (PubMed) · PMC5257257 (PubMed Central)
  31. The MAPK Pathway Regulates Intrinsic Resistance to BET Inhibitors in Colorectal Cancer. Ma Y, Wang L, Neitzel LR, Loganathan SN, Tang N, Qin L, Crispi EE, Guo Y, Knapp S, Beauchamp RD, Lee E, Wang J (2017) Clin Cancer Res 23(8): 2027-2037
    › Primary publication · 27678457 (PubMed) · PMC5368030 (PubMed Central)
  32. Reconstitution of the Cytoplasmic Regulation of the Wnt Signaling Pathway Using Xenopus Egg Extracts. Hyde AS, Hang BI, Lee E (2016) Methods Mol Biol : 101-9
    › Primary publication · 27590156 (PubMed) · PMC5567996 (PubMed Central)
  33. Identification of a Paralog-Specific Notch1 Intracellular Domain Degron. Broadus MR, Chen TW, Neitzel LR, Ng VH, Jodoin JN, Lee LA, Salic A, Robbins DJ, Capobianco AJ, Patton JG, Huppert SS, Lee E (2016) Cell Rep 15(9): 1920-9
    › Primary publication · 27210761 (PubMed) · PMC4889555 (PubMed Central)
  34. The Small Molecule IMR-1 Inhibits the Notch Transcriptional Activation Complex to Suppress Tumorigenesis. Astudillo L, Da Silva TG, Wang Z, Han X, Jin K, VanWye J, Zhu X, Weaver K, Oashi T, Lopes PE, Orton D, Neitzel LR, Lee E, Landgraf R, Robbins DJ, MacKerell AD, Capobianco AJ (2016) Cancer Res 76(12): 3593-603
    › Primary publication · 27197169 (PubMed) · PMC4911243 (PubMed Central)
  35. Wnt pathway activation by ADP-ribosylation. Yang E, Tacchelly-Benites O, Wang Z, Randall MP, Tian A, Benchabane H, Freemantle S, Pikielny C, Tolwinski NS, Lee E, Ahmed Y (2016) Nat Commun : 11430
    › Primary publication · 27138857 (PubMed) · PMC4857404 (PubMed Central)
  36. Wnt/Wingless Pathway Activation Is Promoted by a Critical Threshold of Axin Maintained by the Tumor Suppressor APC and the ADP-Ribose Polymerase Tankyrase. Wang Z, Tacchelly-Benites O, Yang E, Thorne CA, Nojima H, Lee E, Ahmed Y (2016) Genetics 203(1): 269-81
    › Primary publication · 26975665 (PubMed) · PMC4858779 (PubMed Central)
  37. GLI3 Links Environmental Arsenic Exposure and Human Fetal Growth. Winterbottom EF, Fei DL, Koestler DC, Giambelli C, Wika E, Capobianco AJ, Lee E, Marsit CJ, Karagas MR, Robbins DJ (2015) EBioMedicine 2(6): 536-43
    › Primary publication · 26288817 (PubMed) · PMC4535308 (PubMed Central)
  38. Inhibition of Wnt/β-catenin pathway promotes regenerative repair of cutaneous and cartilage injury. Bastakoty D, Saraswati S, Cates J, Lee E, Nanney LB, Young PP (2015) FASEB J 29(12): 4881-92
    › Primary publication · 26268926 (PubMed) · PMC4653050 (PubMed Central)
  39. Small-molecule high-throughput screening utilizing Xenopus egg extract. Broadus MR, Yew PR, Hann SR, Lee E (2015) Methods Mol Biol : 63-73
    › Primary publication · 25618336 (PubMed) · PMC4492114 (PubMed Central)
  40. Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis. Li B, Flaveny CA, Giambelli C, Fei DL, Han L, Hang BI, Bai F, Pei XH, Nose V, Burlingame O, Capobianco AJ, Orton D, Lee E, Robbins DJ (2014) PLoS One 9(7): e101969
    › Primary publication · 25003333 (PubMed) · PMC4086981 (PubMed Central)
  41. Pyrvinium attenuates Hedgehog signaling downstream of smoothened. Li B, Fei DL, Flaveny CA, Dahmane N, Baubet V, Wang Z, Bai F, Pei XH, Rodriguez-Blanco J, Hang B, Orton D, Han L, Wang B, Capobianco AJ, Lee E, Robbins DJ (2014) Cancer Res 74(17): 4811-21
    › Primary publication · 24994715 (PubMed) · PMC4321822 (PubMed Central)
  42. The Drosophila MCPH1-B isoform is a substrate of the APCCdh1 E3 ubiquitin ligase complex. Hainline SG, Rickmyre JL, Neitzel LR, Lee LA, Lee E (2014) Biol Open 3(7): 669-76
    › Primary publication · 24972868 (PubMed) · PMC4154303 (PubMed Central)
  43. Reconstitution Of β-catenin degradation in Xenopus egg extract. Chen TW, Broadus MR, Huppert SS, Lee E (2014) J Vis Exp (88)
    › Primary publication · 24962160 (PubMed) · PMC4133086 (PubMed Central)
  44. TRIP/NOPO E3 ubiquitin ligase promotes ubiquitylation of DNA polymerase η. Wallace HA, Merkle JA, Yu MC, Berg TG, Lee E, Bosco G, Lee LA (2014) Development 141(6): 1332-41
    › Primary publication · 24553286 (PubMed) · PMC3943184 (PubMed Central)