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Carol J. Thiele, Ph.D.

Portait Photo of Carol Thiele
Pediatric Oncology Branch
Head, Cell and Molecular Biology Section
Senior Investigator
Center for Cancer Research
National Cancer Institute
Building 10 - Hatfield CRC, Room 1W- 3940 (office)
Building 10 - Hatfield CRC, Room 1W-5819 (lab)
Bethesda, MD 20892-1928

Thiele's Video Cast

Produced and edited by Natalie Giannosa


Dr. Thiele received her Ph.D. in Microbiology and Immunology from the University of California, Los Angeles. She completed her postdoctoral research as a Cancer Research Institute and a Damon Runyon-Walter Winchell Fellow at the NCI. Dr. Thiele was one of the founding editors of Cell Death & Differentiation, and has served on the editorial boards of Cell Death & Differentiation, Cancer Research and Molecular Cancer Therapeutics. Dr. Thiele was Chair of the AACR Women in Cancer Research and has a long-standing interest in developing programs so that young scientific investigators can realize their potential. As the Chief of the Cell and Molecular Biology Section in the Pediatric Oncology Branch, Dr. Thiele's scientific interest is in the field of cancer biology with a special emphasis on pediatric neuroectodermal tumors and neuronal development. She has been involved in the organization of the Advances in Neuroblastoma Research Association (ANRA). Her research strives to understand molecular mechanisms involved in the pathogenesis of neuroblastoma tumors and utilizes insights gleaned from these studies to develop novel therapeutic strategies for pediatric tumors.


Every year approximately 700 cases of Neuroblastoma (NB) and 210 cases of Ewings' sarcoma (EWS) are diagnosed in children less than 20 yrs of age. Despite the progress made in the development of clinical/genetic staging systems for NB and EWS, half will succumb to disease despite multi-modality therapy, while survivors are frequently left with debilitating sequelae due to therapy. For this reason, more effective and less toxic therapies are needed. Over the last 15 years, we have focused our basic research on NB and retinoic acid (RA) induced differentiation. NB tumors contain a number of genetic alterations yet despite these alterations, RA can inhibit cell growth, suppress tumorigenicity and induce differentiation. Our finding that the RA induced growth arrest and differentiation of NB cell lines is accompanied by a transcriptional decrease in the expression of theMYCN proto-oncogene (whose amplification mark NB with the worst prognosis) provided an important pre-clinical rationale for RA-therapy in NB. The inclusion of retinoids significantly enhanced overall survival with few side effects. Retinoids are now part of the standard therapy for high-risk NB patients.

Using model systems we have detailed; 1) the role of MYCN in NB cell cycle progression, 2) the identification of p27 as a key inhibitor of NB cell cycle progression, 3) how RARbeta was a key transcriptional mediator of RA induced control of NB cell growth and differentiation 4) and how the development of retinoid resistance could be overcome with inhibitors of growth factor signaling. We have identified a number of genes that are regulated under physiological and pharmacologic levels of retinoids that have been key in understanding the underlying developmental programs that mediate neuroblastoma cell differentiation, survival and chemoresistance. Our identification of BDNF/TrkB/PI3K/AKT as a key pathway mediating NB cell survival and chemoresistance has led to the development of pre-clinical models that identified that kinase inhibitors of PI3K/AKT/mTOR pathways would enhance the efficacy of cytotoxic therapy. Currently Phase I trials are evaluating protocols to implement such a strategy. We have identified a novel 1p36 NB tumor suppressor gene, CASZ1, and determined that EZH2 mediated epigenetic suppression of the remaining allele and 1pLOH were the mechanisms leading to the biallelic inactivation of this tumor suppressor gene. Current studies are examining how retinioids relieve epigenetic suppression in NB and how targeting the epigenome may lead to novel, less toxic therapies.

This page was last updated on 7/9/2014.