Wafik S. El-Deiry, M.D. Ph.D.
Professor, Departments of Medicine (Hematology/Oncology), Genetics, and Pharmacology
Co-Program Leader, Radiation Biology Program, Abramson Comprehensive Cancer Center, Associate Director for Physician-Scientist Training Hematology-Oncology Division

Cancer Biology Program

Address

437 Clinical Rsch Bldg (Office)
440 Clinical Rsch Bldg (Lab)
415 Curie Boulevard
Philadelphia, PA 19104-6140

Office tel.: 215-898-9015
Lab tel.: 215 898-9072
Fax: 215 573-9139
E-mail: wafik@mail.med.upenn.edu

Administrative Assistant:
Shannone Nicholson
University of Pennsylvania School of Medicine Department of Medicine Hematology/Oncology Division
415 Curie Blvd., 427 CRB
Philadelphia, PA 19104
Tel: 215-573-9661
Fax: 215-898-0814
Email: nichols4@mail.med.upenn.edu


Link(s)

Dr. El-Deiry's Hematology/Oncology web page

Cancer Biology and Therapy (A peer reviewed journal edited by Dr. El-Deiry)

ISI Interview with Dr. El-Deiry

Tumor Suppressor Genes (A 2 volume text edited by Dr. El-Deiry):

Dr. El-Deiry's BMB graduate group page

Dr. El-Deiry's Pharmacology group page

Highly Cited Researcher

Death Receptors Book

Bioluminescence Imaging

Drug Development

Littlefield-AACR Award

Education

University of Miami: BS (Chemistry), 1981.

University of Miami School of Medicine: Ph.D. (Biochemistry), 1987.

University of Miami School of Medicine: M.D., 1987.

Johns Hopkins University: Post-graduate training (Internal Medicine, Oncology, Molecular Genetics of Cancer), 1987-1994.

Research Interests

1. p53 and TRAIL signaling
2. Novel anti-cancer therapeutics
3. In vivo molecular imaging

Key words: P53, apoptosis, transcription, cancer, p21, TRAIL, GI cancer, drug resistance, in-vivo bioluminescence imaging, BRCA1, transformation, repair, caspase activation, tumor suppression.

Search PubMed for articles

Description of Research

The major interest of the lab in recent years has been to understand the mechanism of action of the tumor suppressor p53 and the contribution of its downstream target genes to cellular growth control. Analysis of this pathway led to our identification of a number of genes directly regulated by p53 and which can inhibit cell cycle progression (p21WAF1), induce apoptosis (KILLER/DR5, Bid, caspase 6, Traf4 and others) or activate DNA repair (DDB2). Insights have emerged into the tissue specificity of the DNA damage response in vivo as well as into the mechanism by which wild-type p53 sensitizes cells to killing by anti-cancer drugs. Efforts have been directed at understanding regulation of p53 activity through control of its stability as well as its selectivity in target gene activation. An area of focus in the lab that emerged from our work on p53 involves analysis of the extrinsic cell death pathway and its activation by the death ligand TRAIL. Our work on the TRAIL pathway has involved analysis of mechanisms of sensitivity and resistance of cancer cells, exploration of intracellular signaling events involved in regulating caspase activation and studies of how cell death occurs with respect to mitochondrial involvement.

A new direction for the lab within the last several years has involved the development and application of non-invasive in vivo imaging technologies for cancer research. We have used bioluminescence and fluorescence to image tumors in vivo as well as molecular events occurring within the tumors including chemotherapy-induced gene expression changes. Other exciting applications include the ability to image protein-protein interaction in vivo and the ability to image the effects of genetic changes on tumor cell transformation and tumor growth in vivo. Of particular interest are efforts to incorporate genetic alterations (oncogene overexpression into primary human epithelial cells from the human esophagus or human mammary gland; tumor suppressor gene silencing including inducible systems) and imaging reporters/probes for longitudinal multi-modality in vivo molecular imaging in small animals. Efforts include validation of models through studies involving microarray comparisons with human tumors. These capabilities and new technologies are enabling the development of cell-based assays, small molecule screens, animal models, and imaging probes to accelerate research on cancer biology, drug development, drug target validation, as well as biomarker development for clinical use in cancer diagnosis and therapeutic monitoring.

The goal of the laboratory is to translate basic knowledge in the areas of tumor suppressor genes and cell death signaling into novel diagnostic/therapeutic modalities in the clinic. Recent efforts to develop small molecule therapeutics are proceeding in the direction of creating and testing structural analogues through medicinal chemistry and are involving collaborations and interactions with the NCI Developmental Therapeutics Program, the Broad Institute at MIT, The Penn MLSCN, as well as Biotech companies including Oncoceutics and Progenra. We are also investing efforts to understand the impact of the tumor microenvironment including hypoxia and stem cell composition on therapeutic sensitivity. Mechanistic studies, target validation, preclinical toxicology and pharmacokinetics are part of the effort that involves multiple collaborators to achieve specific translational goals. Efforts are progressing to develop therapeutic agents and combinations including TRAIL, radiation, classical chemotherapy and novel small molecules targeting drug-resistant cancer for implementation through Phase I/II clinical protocols. This is a rich laboratory environment for learning about cancer biology, preclinical models of human cancer, and the complexities of translational drug development research targeting key molecular events required for transformation and tumor progression.

Recent Publications

Ricci, M.S., Kim, S-H., Ogi, K., Plastaras, J.P., Ling, J., Wang, W., Jin, Z., Liu, Y.Y., Dicker, D.T., Chiao, P.J., Flaherty, K.T., Smith, C.D., and *El-Deiry, W.S. (2007). Repression of TRAIL-induced Mcl-1 and CIAP2 expression by c-Myc or Bay 43-9006 (Sorafenib) sensitizes resistant human cancer cells to TRAIL-induced death. Cancer Cell. 12, 66-80. Accompanying Preview in July 2007 Cancer Cell)

Plastaras, J.P., Kim, S-H., Liu, Y., Dicker, D.T., Dorsey, J.F., McDonough, J., Cerniglia, G., Rajendran, R., Gupta, A., Rustgi, A.K., Diehl, J.A., Smith, C., Flaherty, K., and *El-Deiry, W.S. (2007). Cell cycle and schedule dependent anti-tumor effects of Sorafenib combined with radiation. Cancer Research, in press.

Tumeh, P.C., Lerner, J.M., Dicker, D.T., and *El-Deiry, W.S. (2007). Differentiation of vascular and non-vascular skin spectral signatures using in vivo hyperspectral radiometric imaging: Implications for monitoring angiogenesis. Cancer Biol. Ther. 6, 447-453

Yang, W-S., Rozan, L.M., McDonald, E.R., III, Matthew, E., Wang, W., Dicker, D.T., and *El-Deiry, W.S. (2007). Caspase-8/-10 associated RING domain proteins (CARPs) 1/2 are novel ubiquitin ligases that promote MDM2-independent p53 and phospho-p53ser20 degradation. J. Biol. Chem. 282., 3273-3281.

Rozan, L.M., and El-Deiry, W.S. (2007). p53 downstream target genes and tumor suppression: A classical view in evolution. Cell Death Diff. 14, 3-9.

Kim, S-H., Nakagawa, H., Navaraj, A., Naomoto, Y., Klein-Szanto, A.J.P., Rustgi, A.K., and El-Deiry, W.S. (2006). Tumorigenic conversion of primary human esophageal epithelial cells using oncogene combinations in the absence of exogenous Ras. Cancer Research. 66, 10415-10424. (Featured on the Cover; November 1, 2006)

LAB

Rotation Projects

Please make an appointment to discuss ongoing work and available projects.

Personnel

Junaid Abdulghani, M.D. Ph.D., Post-doctoral Scientist (Jefferson)
Joe Ackerman, Ph.D., Post-doctoral Scientist (Penn State)
David T. Dicker, Research Specialist (Flow and Multispectral Imaging)
Nathan Dolloff, Ph.D., Post-doctoral Scientist (Drexel)
Wafik S. El-Deiry, M.D., Ph.D. (Professor and Lab Director)
Niklas Finnberg, Ph.D., Post-doctoral Scientist (Karolinska Institute)
Lori Hart, Ph.D., Post-doctoral Scientist (Wake Forest U.)
Sharyn Katz, M.D., Assistant Professor (Penn Radiology)
Seok-Hyun Kim, M.D. Ph.D., Post-doctoral Scientist (Yonsei Medical University)
Kageaki Kuribayashi, M.D. Ph.D., Post-doctoral Scientist (Sapporo Medical University)
Yvette Liu, Imaging Specialist (Bioluminescence & Fluorescence Tomography)
Elizabeth Matthew, Ph.D., Post-doctoral Scientist (U. Cincinnati)
Patrick Mayes, Graduate Student (Pharmacology)
Arunasalam Navaraj, Ph.D., Post-doc. Scientist (Northwestern U.)
Shannone Nicholson, Administrative Assistant
Kimberly Scata, Ph.D., Post-doctoral Scientist (Penn)
Raluca Tavaluc, Visiting Undergraduate (Georgetown)
Xiaobing Tian, Ph.D., Post-doctoral Scientist (Medicinal Chemist; Jefferson)
Wenge Wang, M.D. Ph.D., Post-doctoral Scientist (Columbia U.)
Wensheng Yang, Ph.D., Post-doctoral Scientist (Clemson U.)
Lanlan Zhou, Graduate Student (Bioengineering)