Carol J. Thiele, Ph.D.
Carol J. Thiele, Ph.D.
Senior Investigator
Head, Cell and Molecular Biology Section

Dr. Thiele leads a research program which develops novel therapies for children with solid tumors using state-of-the-art biologic and genomic analyses of tumors and normal counterparts. She pioneered studies using retinoids to “target” the MYCN oncogene and control tumor growth. These led to clinical studies which showed that retinoids improved outcomes for children with high-risk neuroblastoma.

Her section has developed pre-clinical models and genetically engineered mice (GEMs) to study mechanisms of neuroblastoma tumorigenesis and assess novel therapeutic interventions. Ongoing studies are aimed at understanding epigenetic/chromatin based mechansims to re-program and differentiate neuroblastoma tumor cells.

Areas of Expertise
1) pediatric tumors, 2) neuroblastoma, 3) retinoids, 4) epigenetics, 5) signal transduction pathways, 6) neurotrophins

Contact Info

Carol J. Thiele, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 10 - Hatfield CRC, Room 1W- 3940 (office)
Bethesda, MD 20892-1928
301-496-1543
ct47a@nih.gov

 

Cell and Molecular Biology Section

Every year approximately 700 cases of neuroblastoma (NB) and 210 cases of Ewings' sarcoma (EWS) are diagnosed in children less than 20 years of age. Half will fail conventional therapy. Despite the progress made in the development of clinical/genetic-based staging systems for NB and EWS the prognosis for patients with unfavorable disease remains dismal. The focus of the Cell and Molecular Biology Section has been to develop a comprehensive understanding of the biology of peripheral neuroectodermal tumors cells. We do so by developing in vitro and in vivo modeling systems that will enable genetic interrogation of the biologic systems of tumor cells and their normal counterparts. The insights gained from these studies serve as a platform for the development of novel therapies for the treatment of children with these diseases.

A number of genetic alterations have been identified in neuroblastoma tumors which are thought to contribute to tumorigenicity. Despite these genetic alterations, retinoids (derivatives of Vitamin A) are capable of arresting cell growth, inducing differentiation and suppressing tumorigenicity. Thus by activating alternative intracellular signaling programs we may be able to bypass genetic defects and restore growth control and induction of differentiation.

ra treatment

Project I: The BDNF/TrkB/PI3-Kinase/AKT Pathway Is Important in the Survival and Metastatic Capability of NB Tumor Cells.  The specific aims of this project are:

  1. To identify and characterize the molecular mechanisms mediating these processes; and
  2. To evaluate the therapeutic potential of targeting downstream signaling intermediaries of the PI3-Kinase/AKT pathway to enhance chemosensitivity and inhibit metastasis and angiogenesis. 

Project II: Clinical, Histopathologic and Genetic Evidence Indicates that Alterations in the Regulation of Normal Development Contribute to NB Tumorigenesis.  The specific aims of this project are:

  1. To identify and characterize NB tumor-initiating cells/cancer stem cells;
  2. To identify the epigenetic pathways dysregulated in NB by using chemical and siRNA screens to identify comounds that target these epigenetic pathways; and
  3. To study the epigenetic mechanisms regulating NB differentiation by using chemical and small molecule screens to identify agents that stimulate differentiation.

CBMS Research Data

  CHLA-LAN-5 neuroblastoma cell growth in vitro - Note neuroblastoma cells are motile and clumps of cells aggregate. Cells continue to proliferate until the entire bottom of the flask is confluent.

  CHLA-LAN-5 neuroblastoma cells treated with retinoic acid in vitro. -  Note neuroblastoma cells growing in clumps, disperse and begin to extend short extensions. By 48hrs cells have ceased to proliferate and the extension of processes increases. Subsequently cells begin to re-aggregate and the clumps are tethered to each other and the bottom of the flask by longer neuritic-like extensions. In a “tug-of-war” like fashion the clumps of cells move around the flask and aggregate into even larger balls of cells. 

 

CBMS Group 2014

The CMBS Section 2014

Scientific Focus Areas:
Cancer Biology, Chromosome Biology, Developmental Biology, Genetics and Genomics, Stem Cell Biology

View Dr. Thiele's PubMed Summary.

Selected Key Publications
  1. Liu Z, Li W, Ma X, Ding N, Spallotta F, Southon E, Tessarollo L, Gaetano C, Mukouyama YS, Thiele CJ
    J. Biol. Chem. 289: 29801-29816, 2014. [ Journal Article ]
  2. Wang C, Liu Z, Woo CW, Li Z, Wang L, Wei JS, Marquez VE, Bates SE, Jin Q, Khan J, Ge K, Thiele CJ
    Cancer Res. 72: 315-324, 2012. [ Journal Article ]
  3. Li Z, Jaboin J, Dennis PA, Thiele CJ
    Cancer Res. 65: 2070-2075, 2005. [ Journal Article ]
  4. Liu Z, Yang X, Li Z, McMahon C, Sizer C, Barenboim-Stapleton L, Bliskovsky V, Mock B, Ried T, London WB, Maris J, Khan J, Thiele CJ
    Cell Death Differ. 18: 1174-1183, 2011. [ Journal Article ]
  5. Thiele CJ, Reynolds CP, Israel MA
    Nature. 313: 404-406, 1985. [ Journal Article ]

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.

Position Number of Positions Contact E-mail Contact Name Contact Phone
Postdoctoral Fellow 1

ct47a@nih.gov

Carol J. Thiele, Ph.D. 301.496.1543
Name Position
Fidelia Acevedo Program Assistant
Deblina Banerjee Ph.D. Postdoctoral Fellow (Visiting)
Barbara Kunzler Souza M.Sc. Predoctoral Fellow (Visiting)
Norris Lam B.S. Postbaccalaureate Fellow
Zhihui Liu Ph.D. Staff Scientist
Seiichi Odate M.D., Ph.D. Postdoctoral Fellow (Visiting)
Neeraj Prasad Special Volunteer
Veronica Veschi M.D. Predoctoral Fellow (Visiting)

News

2011 FARE Awards

  • Doo-Yi Oh – Retinoids (RA) Relieve EZH2- mediated Epigenetic Suppression of Neuroblastoma (NB) Differentiation
  • Shuang Yan, MD, PhDNeuroblastoma Tumor Initiating Cells Express CD22 Making Them Susceptible to HA22 anti-CD22 Immunotoxin-induced Cell Death

Advances In Neuroblastoma Research 2010 – Best Abstracts

  • Ryan VirdenIdentification and Analysis of Critical Domains in the Neuroblastoma Tumor Suppressor Gene CASZ1
  • Chunxi WangEZH2 Mediates Epigenetic Silencing of Candidate Neuroblastoma Tumor Suppressor Gene CASZ1
  • Zhihui Liu, PhD Haploinsufficiency of Candidate Tumor Suppressor Gene CASZ1 Blocks Embryonic Stem Cell Neurogenesis

2010 NCI Director’s Intramural Innovation Awards

  • Zhihui Liu, PhD Genetic  Screen of Candidate Tumor Suppressor Genes for Neural Crest-derived Tumors

 

Research

 

Cell and Molecular Biology Section

Every year approximately 700 cases of neuroblastoma (NB) and 210 cases of Ewings' sarcoma (EWS) are diagnosed in children less than 20 years of age. Half will fail conventional therapy. Despite the progress made in the development of clinical/genetic-based staging systems for NB and EWS the prognosis for patients with unfavorable disease remains dismal. The focus of the Cell and Molecular Biology Section has been to develop a comprehensive understanding of the biology of peripheral neuroectodermal tumors cells. We do so by developing in vitro and in vivo modeling systems that will enable genetic interrogation of the biologic systems of tumor cells and their normal counterparts. The insights gained from these studies serve as a platform for the development of novel therapies for the treatment of children with these diseases.

A number of genetic alterations have been identified in neuroblastoma tumors which are thought to contribute to tumorigenicity. Despite these genetic alterations, retinoids (derivatives of Vitamin A) are capable of arresting cell growth, inducing differentiation and suppressing tumorigenicity. Thus by activating alternative intracellular signaling programs we may be able to bypass genetic defects and restore growth control and induction of differentiation.

ra treatment

Project I: The BDNF/TrkB/PI3-Kinase/AKT Pathway Is Important in the Survival and Metastatic Capability of NB Tumor Cells.  The specific aims of this project are:

  1. To identify and characterize the molecular mechanisms mediating these processes; and
  2. To evaluate the therapeutic potential of targeting downstream signaling intermediaries of the PI3-Kinase/AKT pathway to enhance chemosensitivity and inhibit metastasis and angiogenesis. 

Project II: Clinical, Histopathologic and Genetic Evidence Indicates that Alterations in the Regulation of Normal Development Contribute to NB Tumorigenesis.  The specific aims of this project are:

  1. To identify and characterize NB tumor-initiating cells/cancer stem cells;
  2. To identify the epigenetic pathways dysregulated in NB by using chemical and siRNA screens to identify comounds that target these epigenetic pathways; and
  3. To study the epigenetic mechanisms regulating NB differentiation by using chemical and small molecule screens to identify agents that stimulate differentiation.

CBMS Research Data

  CHLA-LAN-5 neuroblastoma cell growth in vitro - Note neuroblastoma cells are motile and clumps of cells aggregate. Cells continue to proliferate until the entire bottom of the flask is confluent.

  CHLA-LAN-5 neuroblastoma cells treated with retinoic acid in vitro. -  Note neuroblastoma cells growing in clumps, disperse and begin to extend short extensions. By 48hrs cells have ceased to proliferate and the extension of processes increases. Subsequently cells begin to re-aggregate and the clumps are tethered to each other and the bottom of the flask by longer neuritic-like extensions. In a “tug-of-war” like fashion the clumps of cells move around the flask and aggregate into even larger balls of cells. 

 

CBMS Group 2014

The CMBS Section 2014

Scientific Focus Areas:
Cancer Biology, Chromosome Biology, Developmental Biology, Genetics and Genomics, Stem Cell Biology

Publications

View Dr. Thiele's PubMed Summary.

Selected Key Publications
  1. Liu Z, Li W, Ma X, Ding N, Spallotta F, Southon E, Tessarollo L, Gaetano C, Mukouyama YS, Thiele CJ
    J. Biol. Chem. 289: 29801-29816, 2014. [ Journal Article ]
  2. Wang C, Liu Z, Woo CW, Li Z, Wang L, Wei JS, Marquez VE, Bates SE, Jin Q, Khan J, Ge K, Thiele CJ
    Cancer Res. 72: 315-324, 2012. [ Journal Article ]
  3. Li Z, Jaboin J, Dennis PA, Thiele CJ
    Cancer Res. 65: 2070-2075, 2005. [ Journal Article ]
  4. Liu Z, Yang X, Li Z, McMahon C, Sizer C, Barenboim-Stapleton L, Bliskovsky V, Mock B, Ried T, London WB, Maris J, Khan J, Thiele CJ
    Cell Death Differ. 18: 1174-1183, 2011. [ Journal Article ]
  5. Thiele CJ, Reynolds CP, Israel MA
    Nature. 313: 404-406, 1985. [ Journal Article ]

Biography

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.

Positions

Position Number of Positions Contact E-mail Contact Name Contact Phone
Postdoctoral Fellow 1

ct47a@nih.gov

Carol J. Thiele, Ph.D. 301.496.1543

Team

Name Position
Fidelia Acevedo Program Assistant
Deblina Banerjee Ph.D. Postdoctoral Fellow (Visiting)
Barbara Kunzler Souza M.Sc. Predoctoral Fellow (Visiting)
Norris Lam B.S. Postbaccalaureate Fellow
Zhihui Liu Ph.D. Staff Scientist
Seiichi Odate M.D., Ph.D. Postdoctoral Fellow (Visiting)
Neeraj Prasad Special Volunteer
Veronica Veschi M.D. Predoctoral Fellow (Visiting)

News

News

2011 FARE Awards

  • Doo-Yi Oh – Retinoids (RA) Relieve EZH2- mediated Epigenetic Suppression of Neuroblastoma (NB) Differentiation
  • Shuang Yan, MD, PhDNeuroblastoma Tumor Initiating Cells Express CD22 Making Them Susceptible to HA22 anti-CD22 Immunotoxin-induced Cell Death

Advances In Neuroblastoma Research 2010 – Best Abstracts

  • Ryan VirdenIdentification and Analysis of Critical Domains in the Neuroblastoma Tumor Suppressor Gene CASZ1
  • Chunxi WangEZH2 Mediates Epigenetic Silencing of Candidate Neuroblastoma Tumor Suppressor Gene CASZ1
  • Zhihui Liu, PhD Haploinsufficiency of Candidate Tumor Suppressor Gene CASZ1 Blocks Embryonic Stem Cell Neurogenesis

2010 NCI Director’s Intramural Innovation Awards

  • Zhihui Liu, PhD Genetic  Screen of Candidate Tumor Suppressor Genes for Neural Crest-derived Tumors

 

Lab Life