Wafik El-Deiry

Wafik El-Deiry
Born1961 (age 64–65)
Egypt
CitizenshipUnited States
Education
Known forDiscovery of WAF1/p21, p53 binding site
Scientific career
FieldsOncology, Cancer research
Workplaces

Wafik El-Deiry (born 1961) is an Egyptian-American physician and cancer researcher who is the associate dean for oncologic sciences at the Warren Alpert Medical School, Brown University.[1] He is also the director of the Cancer Center at Brown University, and the director of the Joint Program in Cancer Biology at Brown University and its affiliated hospitals.[2][3][4][5]

Career

El-Deiry was born in Egypt and immigrated to the United States in 1978.[1] He was formerly a professor of Medicine and Chief of Hematology/Oncology at the Penn State Milton S. Hershey Medical Center. He also served as the associate director for Translational Research and Interim Cancer Center Director at Penn State University.[6] He held an endowed chair in hematology-oncology while at Penn State University: the Rose Dunlap Division Chair in Hematology-Oncology.[7]

Research

El-Deiry made the discoveries of the consensus binding site for p53 and the discovery of WAF1 while working with Bert Vogelstein at Johns Hopkins University. p21(WAF1) was the first mammalian cell cycle inhibitor to be discovered, and was found independently by Wade Harper and Steve Elledge as a CDK2-interacting protein p21(CIP1),[8] Yue Xiong and David Beach as a cyclin-CDK-PCNA interacting protein (p21),[9] and as a senescence derived inhibitor by Noda.[10] Multiple CDK inhibitors have become approved as cancer therapeutics, including palbociclib, abemaciclib and ribociclib. In 2017, El-Deiry's group discovered a micro-RNA family that inhibits CDK4/6.[11][12] In 2021, Dr. El-Deiry discussed the discovery of WAF1 in an interview entitled "Persistence. Agility. Cancer Research with Dr. Wafik El-Deiry" for The Medicine Mentors Podcast.[13]

He was recognized through an award from the American Cancer Society in 2016.[14]

As an independent investigator at University of Pennsylvania, El-Deiry discovered TRAIL death receptor 5 (DR5)[15][16] in 1997. His group was first to combine gene silencing with bioluminescence imaging in vivo[17][18] and to use molecular imaging for drug screening.[19] His group created a knockout mouse of death receptor 5 (DR5) that shows reduced apoptosis in vivo after exposure to gamma-radiation,[20] and increased tumor susceptibility in tumor-prone genetic backgrounds.[21] The mechanism by which cell death occurs in vivo after radiation or other DNA damage has remained an important question that has been studied by Michael B. Kastan, Scott W. Lowe, Karen Vousden, and others. El-Deiry's contribution was to define the role of the extrinsic cell death pathway through p53 regulation of death receptor 5.

El-Deiry worked on drug synergies and discovered a potent cancer therapeutic interaction between TRAIL and sorafenib.[22][23] In 2013, his group reported a TRAIL-inducing compound TIC10 as a novel cancer therapeutic and dual inhibitor of ERK and Akt.[24] TIC10 (also known as ONC201) could cross the blood-brain barrier and treat glioblastoma brain cancer in mice.[25]

Professional activities

In 2001, El-Deiry became the Founding Editor-in-Chief of the peer-reviewed journal Cancer Biology and Therapy.[26]

He is also a member of the American Society for Clinical Investigation (1999), the Association of American Physicians (2008), is a Fellow of the American College of Physicians (2012), and a member of the Johns Hopkins University Society of Scholars (2014).[27][28]

As a medical oncologist El-Deiry specializes in the care of patients with colorectal cancer. His clinical research demonstrated variability in 5-fluorouracil plasma levels in patients with colorectal cancer.[29] El-Deiry showed that pharmacokinetically guided dosing of 5-fluorouracil chemotherapy is associated with lower levels of toxicity among patients with stage II/III as well as stage IV colorectal cancer.[30][31] Toxicity from chemotherapy is associated with worse quality of life in patients with cancer. In 2017, his group showed that the tumor suppressor protein p53 represses the DPYD gene in 5-fluorouracil-treated cells and that tumor cells with mutated p53 have higher levels of DPYD thereby becoming resistant to 5-fluorouracil.[32] DPYD is involved in the metabolism of 5-fluorouracil and patients with DPD-deficiency have predictable toxicity from 5-fluorouracil.

El-Deiry was appointed co-Editor-in-Chief of the journal Oncotarget on June 23, 2024.[33]

El-Deiry was the subject of a Retraction Watch article on June 10, 2025.[34]

References

  1. 1 2 The Cancer Letter (November 3, 2023). "Wafik El-Deiry on finding p53's binding site and his journey from Egypt to Brown". The Cancer Letter. Retrieved May 22, 2024.
  2. ↑ "Wafik El-Deiry Named Inaugural Associate Dean for Oncologic Sciences".
  3. ↑ Communications, the Office of Biomedical (22 September 2020). "Brown establishes new Cancer Center dedicated to research, clinical developments". Brown University. Retrieved 2021-08-05.
  4. ↑ "Cancer Center at Brown University Established - The ASCO Post". ascopost.com. Retrieved 2021-08-05.
  5. ↑ Alexa Gagosz (July 30, 2021). "Could Rhode Island become the next cancer research hub?". The Boston Globe. Retrieved 2021-08-05.
  6. ↑ "El-Deiry to serve as Cancer Institute interim director".
  7. ↑ "Cancer Biology and Therapy Editor Wafik El-Deiry named as Chief of Hematology/Oncology at Penn State". Cancer Biology & Therapy. 9 (7): 479–478. 2010. doi:10.4161/cbt.9.7.11846.
  8. ↑ Harper, J. W.; Adami, G. R.; Wei, N.; Keyomarsi, K.; Elledge, S. J. (1993-11-19). "The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases". Cell. 75 (4): 805–816. doi:10.1016/0092-8674(93)90499-g. ISSN 0092-8674. PMID 8242751.
  9. ↑ Xiong, Yue; Hannon, Gregory J.; Zhang, Hui; Casso, David; Kobayashi, Ryuji; Beach, David (1993). "p21 is a universal inhibitor of cyclin kinases". Nature. 366 (6456): 701–704. Bibcode:1993Natur.366..701X. doi:10.1038/366701a0. ISSN 1476-4687. PMID 8259214. S2CID 4362507.
  10. ↑ Noda, Asao; Ning, Yi; Venable, Susan F.; Pereira-Smith, Olivia M.; Smith, James R. (1994). "Cloning of Senescent Cell-Derived Inhibitors of DNA Synthesis Using an Expression Screen". Experimental Cell Research. 211 (1): 90–98. doi:10.1006/excr.1994.1063. PMID 8125163.
  11. ↑ "Researchers Discover Micro-RNA Family that Blocks Key Cancer and Cell Cycle Growth-Promoting Proteins".
  12. ↑ Lulla, Amriti R.; Slifker, Michael J.; Zhou, Yan; Lev, Avital; Einarson, Margret B.; Dicker, David T.; El-Deiry, Wafik S. (2017-12-15). "miR-6883 Family miRNAs Target CDK4/6 to Induce G1 Phase Cell-Cycle Arrest in Colon Cancer Cells". Cancer Research. 77 (24): 6902–6913. doi:10.1158/0008-5472.can-17-1767. PMID 29061672.
  13. ↑ "The Medicine Mentors Podcast: Persistence. Agility. Cancer Research with Dr. Wafik El-Deiry". themedicinementors.libsyn.com. Retrieved 2021-08-05.
  14. ↑ "American Cancer Society honors three from Fox Chase".
  15. ↑ "Novel Death-Receptor Gene Identified: KILLER/DR5 Triggers Cancer Cell Death After Chemotherapy Or Radiation".
  16. ↑ Wu, Gen Sheng; Burns, Timothy F.; McDonald, E. Robert; Jiang, Wen; Meng, Ray; Krantz, Ian D.; Kao, Gary; Gan, Dai-Di; Zhou, Jun-Ying (1997). "KILLER/DR5 is a DNA damage–inducible p53–regulated death receptor gene". Nature Genetics. 17 (2): 141–143. doi:10.1038/ng1097-141. ISSN 1546-1718. PMID 9326928. S2CID 7037468.
  17. ↑ "Molecular Tailoring Of Chemotherapy With Novel Imaging Techniques".
  18. ↑ Wang, Shulin; El-Deiry, Wafik S. (2004-09-15). "Inducible Silencing of KILLER/DR5 In vivo Promotes Bioluminescent Colon Tumor Xenograft Growth and Confers Resistance to Chemotherapeutic Agent 5-Fluorouracil". Cancer Research. 64 (18): 6666–6672. doi:10.1158/0008-5472.can-04-1734. PMID 15374982.
  19. ↑ Wang, Wenge; Kim, Seok-Hyun; El-Deiry, Wafik S. (2006-07-18). "Small-molecule modulators of p53 family signaling and antitumor effects in p53-deficient human colon tumor xenografts". Proceedings of the National Academy of Sciences. 103 (29): 11003–11008. Bibcode:2006PNAS..10311003W. doi:10.1073/pnas.0604507103. ISSN 0027-8424. PMC 1544164. PMID 16835297.
  20. ↑ Finnberg, Niklas; Gruber, Joshua J.; Fei, Peiwen; Rudolph, Dorothea; Bric, Anka; Kim, Seok-Hyun; Burns, Timothy F.; Ajuha, Hope; Page, Robert (2005-03-01). "DR5 Knockout Mice Are Compromised in Radiation-Induced Apoptosis". Molecular and Cellular Biology. 25 (5): 2000–2013. doi:10.1128/mcb.25.5.2000-2013.2005. ISSN 0270-7306. PMC 549384. PMID 15713653.
  21. ↑ Finnberg, Niklas; Klein-Szanto, Andres J.P.; El-Deiry, Wafik S. (2008). "TRAIL-R deficiency in mice promotes susceptibility to chronic inflammation and tumorigenesis". Journal of Clinical Investigation. 118 (1): 111–123. doi:10.1172/jci29900. PMC 2129232. PMID 18079962.
  22. ↑ Ricci, M. Stacey; Kim, Seok-Hyun; Ogi, Kazuhiro; Plastaras, John P.; Ling, Jianhua; Wang, Wenge; Jin, Zhaoyu; Liu, Yingqiu Y.; Dicker, David T. (2007). "Reduction of TRAIL-Induced Mcl-1 and cIAP2 by c-Myc or Sorafenib Sensitizes Resistant Human Cancer Cells to TRAIL-Induced Death". Cancer Cell. 12 (1): 66–80. doi:10.1016/j.ccr.2007.05.006. PMID 17613437.
  23. ↑ Kim, Seok-Hyun; Ricci, M. Stacey; El-Deiry, Wafik S. (2008-04-01). "Mcl-1: A Gateway to TRAIL Sensitization". Cancer Research. 68 (7): 2062–2064. doi:10.1158/0008-5472.can-07-6278. PMID 18381408.
  24. ↑ Allen, Joshua E.; Krigsfeld, Gabriel; Mayes, Patrick A.; Patel, Luv; Dicker, David T.; Patel, Akshal S.; Dolloff, Nathan G.; Messaris, Evangelos; Scata, Kimberly A. (2013-02-06). "Dual Inactivation of Akt and ERK by TIC10 Signals Foxo3a Nuclear Translocation, TRAIL Gene Induction, and Potent Antitumor Effects". Science Translational Medicine. 5 (171): 171ra17. doi:10.1126/scitranslmed.3004828. ISSN 1946-6234. PMC 4535715. PMID 23390247.
  25. ↑ "Small-molecule drug drives cancer cells to suicide".
  26. ↑ "Cancer Biology & Therapy". Taylor & Francis.
  27. ↑ "Society of Scholars inducts new members". 2014-05-06.
  28. ↑ "Cancer Biology & Therapy Editor-in-Chief, Wafik S El-Deiry, MD, PhD, FACP, inducted into the Society of Scholars of the Johns Hopkins University on April 7, 2014". Cancer Biol Ther. 15 (5): 479–480. 2014. doi:10.4161/cbt.28843. PMC 4026066. PMID 24717728.
  29. ↑ Kline, Christina Leah; Sheikh, Hassan S.; Scicchitano, Angelique; Gingrich, Rebecca; Beachler, Cheryl; Finnberg, Niklas K.; Liao, Jason; Sivik, Jeffrey; El-Deiry, Wafik S. (2011-10-01). "Preliminary observations indicate variable patterns of plasma 5-fluorouracil (5-FU) levels during dose optimization of infusional 5-FU in colorectal cancer patients". Cancer Biology & Therapy. 12 (7): 557–568. doi:10.4161/cbt.12.7.18059. ISSN 1555-8576. PMID 21931273.
  30. ↑ Kline, Christina Leah B.; Schiccitano, Angelique; Zhu, Junjia; Beachler, Cheryl; Sheikh, Hassan; Harvey, Harold A.; Mackley, Heath B.; McKenna, Kevin; Staveley-O'Carroll, Kevin (2014). "Personalized Dosing via Pharmacokinetic Monitoring of 5-Fluorouracil Might Reduce Toxicity in Early- or Late-Stage Colorectal Cancer Patients Treated With Infusional 5–Fluorouracil-Based Chemotherapy Regimens". Clinical Colorectal Cancer. 13 (2): 119–126. doi:10.1016/j.clcc.2013.11.001. PMID 24461492.
  31. ↑ Kline, Christina Leah B.; El-Deiry, Wafik S. (2013-08-21). "Personalizing Colon Cancer Therapeutics: Targeting Old and New Mechanisms of Action". Pharmaceuticals. 6 (8): 988–1038. doi:10.3390/ph6080988. PMC 3817731. PMID 24276379.
  32. ↑ Gokare, Prashanth; Finnberg, Niklas K.; Abbosh, Phillip H.; Dai, Jenny; Murphy, Maureen E.; El-Deiry, Wafik S. (2017-08-29). "P53 represses pyrimidine catabolic gene dihydropyrimidine dehydrogenase (DPYD) expression in response to thymidylate synthase (TS) targeting". Scientific Reports. 7 (1): 9711. Bibcode:2017NatSR...7.9711G. doi:10.1038/s41598-017-09859-x. PMC 5575263. PMID 28851987.
  33. ↑ "Oncotarget editorial board". Retrieved November 4, 2025.
  34. ↑ Travis, Kate (2025-06-11). "Apparent NCI director candidate wants 'open, respectful' post-publication peer review while promoting anonymous site that calls sleuths a 'mob'". Retraction Watch. Retrieved 2025-11-04.
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