Faculty

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Robert Charles Seeger, MD
Professor of Pediatrics
Section Head For Research in The Division of Hem Onc Bmt
Pediatrics
CHL Mail Stop 57 Off Campus Los Angeles
+1 323 361 5618

Overview

Dr. Seeger is Professor of Pediatrics in the Keck School of Medicine, Director of Cancer Research Program of the Saban Research Institute, and Division Head for Basic and Translational Research of the Center for Cancer and Blood Diseases at CHLA. Dr. Seeger obtained MD and MS degrees from the University of Oregon School of Medicine, Pediatric training at the University of Minnesota, and research training at the NIH and University College London. Before joining USC in 1989 as a Professor of Pediatrics, he was Professor of Pediatrics at the UCLA School of Medicine.

He is a well-funded investigator and currently is the Principal Investigator of a PPG, an R01, an R33, and two U10s. Dr. Seeger’s therapeutic research deals with immunotherapy strategies that seek to maximize natural killer (NK) cell activity with tumor cell targeting antibodies and with agents that modify the tumor microenvironment milieu to minimize NK suppressive effects of monocytes/macrophages producing IL-6 and TGFß1. His biomarker research, in collaboration with Dr. Shahab Asgharzadeh, has resulted in a 14-gene expression signature (TaqMan® Low Density Array, TLDA) that predicts outcome for children with high-risk metastatic neuroblastoma. He also has developed a second TLDA assay that quantifies expression of 5 neuroblastoma genes in bone marrow and blood with the ability to detect 1 tumor cell/million normal cells. This assay is proving useful for monitoring response and predicting outcome.

Finally, in his role as Principal Investigator of and NCI-funded Neuroblastoma PPG, he Co-Chairs the Scientific Review Committee of the New Approaches to Neuroblastoma Therapy consortium (NANT, see www.nant.org), which sets directions and reviews clinical trial proposals. The NANT is an early-phase clinical trials consortium of 15 institutions in North America that tests new treatments, biomarkers, and imaging for children with refractory or recurrent neuroblastoma. Thus, his expertise includes pre-clinical immunotherapy, biomarker development and application, and early phase clinical trials.

Awards

University of Southern California School: Mellon Mentoring Award, 2011

Willamette University: Distinguished Alumni Citation, 2008

H. Russell Smith Award for Innovation in Pediatric Biomedical Research

Publications

Optimization of a Neural Stem-Cell-Mediated Carboxylesterase/Irinotecan Gene Therapy for Metastatic Neuroblastoma. Mol Ther Oncolytics. 2017 Mar 17; 4:67-76. View in: PubMed

Large-scale isolation and cytotoxicity of extracellular vesicles derived from activated human natural killer cells. J Extracell Vesicles. 2017; 6(1):1294368. View in: PubMed

Recommendations for the standardization of bone marrow disease assessment and reporting in children with neuroblastoma; on behalf of the International Neuroblastoma Response Criteria Bone Marrow Working Group. Cancer. 2016 Dec 16. View in: PubMed

Association of high microvessel avß3 and low PTEN with poor outcome in stage 3 neuroblastoma: rationale for using first in class dual PI3K/BRD4 inhibitor, SF1126. Oncotarget. 2016 Nov 16. View in: PubMed

TGFßR1 Blockade with Galunisertib (LY2157299) Enhances Anti-Neuroblastoma Activity of Anti-GD2 Antibody Dinutuximab (ch14. 18) with Natural Killer Cells. Clin Cancer Res. 2016 Oct 10. View in: PubMed

More than the genes, the tumor microenvironment in neuroblastoma. Cancer Lett. 2016 Sep 28; 380(1):304-14. View in: PubMed

A novel minimal residual disease model of neuroblastoma in mice. J Pediatr Surg. 2016 Jun; 51(6):991-4. View in: PubMed

MYCN controls an alternative RNA splicing program in high-risk metastatic neuroblastoma. Cancer Lett. 2016 Feb 28; 371(2):214-24. View in: PubMed

A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis. Cancer Cell. 2015 Nov 9; 28(5):599-609. View in: PubMed

Pilot study of intravenous melphalan combined with continuous infusion L-S,R-buthionine sulfoximine for children with recurrent neuroblastoma. Pediatr Blood Cancer. 2015 Oct; 62(10):1739-46. View in: PubMed

CASC15-S Is a Tumor Suppressor lncRNA at the 6p22 Neuroblastoma Susceptibility Locus. Cancer Res. 2015 Aug 1; 75(15):3155-66. View in: PubMed

Exosome-Mediated Transfer of microRNAs Within the Tumor Microenvironment and Neuroblastoma Resistance to Chemotherapy. J Natl Cancer Inst. 2015 Jul; 107(7). View in: PubMed

Revised risk estimation and treatment stratification of low- and intermediate-risk neuroblastoma patients by integrating clinical and molecular prognostic markers. Clin Cancer Res. 2015 Apr 15; 21(8):1904-15. View in: PubMed

Age-Dependent Prognostic Effect by Mitosis-Karyorrhexis Index in Neuroblastoma: A Report from the Children's Oncology Group. Pediatr Dev Pathol. 2014 Nov-Dec; 17(6):441-9. View in: PubMed

Drugging MYCN through an Allosteric Transition in Aurora Kinase A. Cancer Cell. 2014 Sep 8; 26(3):414-27. View in: PubMed

Neuroblastoma of undifferentiated subtype, prognostic significance of prominent nucleolar formation, and MYC/MYCN protein expression: a report from the Children's Oncology Group. Cancer. 2013 Oct 15; 119(20):3718-26. View in: PubMed

Lenalidomide overcomes suppression of human natural killer cell anti-tumor functions by neuroblastoma microenvironment-associated IL-6 and TGFß1. Cancer Immunol Immunother. 2013 Oct; 62(10):1637-48. View in: PubMed

Purged versus non-purged peripheral blood stem-cell transplantation for high-risk neuroblastoma (COG A3973): a randomised phase 3 trial. Lancet Oncol. 2013 Sep; 14(10):999-1008. View in: PubMed

Critical role of STAT3 in IL-6-mediated drug resistance in human neuroblastoma. Cancer Res. 2013 Jul 1; 73(13):3852-64. View in: PubMed

Membrane-bound TRAIL supplements natural killer cell cytotoxicity against neuroblastoma cells. J Immunother. 2013 Jun; 36(5):319-29. View in: PubMed

Growth and activation of natural killer cells ex vivo from children with neuroblastoma for adoptive cell therapy. Clin Cancer Res. 2013 Apr 15; 19(8):2132-43. View in: PubMed

The genetic landscape of high-risk neuroblastoma. Nat Genet. 2013 Mar; 45(3):279-84. View in: PubMed

Peripheral neuroblastic tumors with genotype-phenotype discordance: a report from the Children's Oncology Group and the International Neuroblastoma Pathology Committee. Pediatr Blood Cancer. 2013 Mar; 60(3):363-70. View in: PubMed

Clinical significance of tumor-associated inflammatory cells in metastatic neuroblastoma. J Clin Oncol. 2012 Oct 1; 30(28):3525-32. View in: PubMed

Sorafenib inhibits endogenous and IL-6/S1P induced JAK2-STAT3 signaling in human neuroblastoma, associated with growth suppression and apoptosis. Cancer Biol Ther. 2012 May 1; 13(7):534-41. View in: PubMed

Common variation at BARD1 results in the expression of an oncogenic isoform that influences neuroblastoma susceptibility and oncogenicity. Cancer Res. 2012 Apr 15; 72(8):2068-78. View in: PubMed

Immunology and immunotherapy of neuroblastoma. Semin Cancer Biol. 2011 Oct; 21(4):229-37. View in: PubMed

Genotypes of NK cell KIR receptors, their ligands, and Fc? receptors in the response of neuroblastoma patients to Hu14. 18-IL2 immunotherapy. Cancer Res. 2010 Dec 1; 70(23):9554-61. View in: PubMed

Antitumor activity of hu14. 18-IL2 in patients with relapsed/refractory neuroblastoma: a Children's Oncology Group (COG) phase II study. J Clin Oncol. 2010 Nov 20; 28(33):4969-75. View in: PubMed

Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010 Sep 30; 363(14):1324-34. View in: PubMed

Outcome after reduced chemotherapy for intermediate-risk neuroblastoma. N Engl J Med. 2010 Sep 30; 363(14):1313-23. View in: PubMed

Phase II randomized comparison of topotecan plus cyclophosphamide versus topotecan alone in children with recurrent or refractory neuroblastoma: a Children's Oncology Group study. J Clin Oncol. 2010 Aug 20; 28(24):3808-15. View in: PubMed

NF1 is a tumor suppressor in neuroblastoma that determines retinoic acid response and disease outcome. Cell. 2010 Jul 23; 142(2):218-29. View in: PubMed

Prognostic impact of gene expression-based classification for neuroblastoma. J Clin Oncol. 2010 Jul 20; 28(21):3506-15. View in: PubMed

Novel cancer vaccine based on genes of Salmonella pathogenicity island 2. Int J Cancer. 2010 Jun 1; 126(11):2622-34. View in: PubMed

Peripheral blood stem cell support for multiple cycles of dose intensive induction therapy is feasible with little risk of tumor contamination in advanced stage neuroblastoma: a report from the Childrens Oncology Group. Pediatr Blood Cancer. 2010 Apr; 54(4):596-602. View in: PubMed

ATM is down-regulated by N-Myc-regulated microRNA-421. Proc Natl Acad Sci U S A. 2010 Jan 26; 107(4):1506-11. View in: PubMed

Clinicopathological characteristics of ganglioneuroma and ganglioneuroblastoma: a report from the CCG and COG. Pediatr Blood Cancer. 2009 Oct; 53(4):563-9. View in: PubMed

Valpha24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages. J Clin Invest. 2009 Jun; 119(6):1524-36. View in: PubMed

Common variations in BARD1 influence susceptibility to high-risk neuroblastoma. Nat Genet. 2009 Jun; 41(6):718-23. View in: PubMed

ZNF423 is critically required for retinoic acid-induced differentiation and is a marker of neuroblastoma outcome. Cancer Cell. 2009 Apr 7; 15(4):328-40. View in: PubMed

Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children's oncology group study. J Clin Oncol. 2009 Mar 1; 27(7):1007-13. View in: PubMed

Outcome of high-risk stage 3 neuroblastoma with myeloablative therapy and 13-cis-retinoic acid: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2009 Jan; 52(1):44-50. View in: PubMed

Phase I study of ch14. 18 with granulocyte-macrophage colony-stimulating factor and interleukin-2 in children with neuroblastoma after autologous bone marrow transplantation or stem-cell rescue: a report from the Children's Oncology Group. J Clin Oncol. 2009 Jan 1; 27(1):85-91. View in: PubMed

Interleukin-6 in the bone marrow microenvironment promotes the growth and survival of neuroblastoma cells. Cancer Res. 2009 Jan 1; 69(1):329-37. View in: PubMed

An integrated cross-platform prognosis study on neuroblastoma patients. Genomics. 2008 Oct; 92(4):195-203. View in: PubMed

Molecular characterization of the pediatric preclinical testing panel. Clin Cancer Res. 2008 Jul 15; 14(14):4572-83. View in: PubMed

Chromosome 6p22 locus associated with clinically aggressive neuroblastoma. N Engl J Med. 2008 Jun 12; 358(24):2585-93. View in: PubMed

Cdc6 knockdown inhibits human neuroblastoma cell proliferation. Mol Cell Biochem. 2008 Apr; 311(1-2):189-97. View in: PubMed

Sparse representation and Bayesian detection of genome copy number alterations from microarray data. Bioinformatics. 2008 Feb 1; 24(3):309-18. View in: PubMed

De novo identification of MIZ-1 (ZBTB17) encoding a MYC-interacting zinc-finger protein as a new favorable neuroblastoma gene. Clin Cancer Res. 2007 Oct 15; 13(20):6001-9. View in: PubMed

Oncogene MYCN regulates localization of NKT cells to the site of disease in neuroblastoma. J Clin Invest. 2007 Sep; 117(9):2702-12. View in: PubMed

Prognostic significance of gene expression profiles of metastatic neuroblastomas lacking MYCN gene amplification. J Natl Cancer Inst. 2006 Sep 6; 98(17):1193-203. View in: PubMed

A phase I clinical trial of the hu14. 18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children's Oncology Group. Clin Cancer Res. 2006 Mar 15; 12(6):1750-9. View in: PubMed

The MYCN enigma: significance of MYCN expression in neuroblastoma. Cancer Res. 2006 Mar 1; 66(5):2826-33. View in: PubMed

Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study. J Clin Oncol. 2006 Jan 20; 24(3):500-6. View in: PubMed

Chromosome 1p and 11q deletions and outcome in neuroblastoma. N Engl J Med. 2005 Nov 24; 353(21):2243-53. View in: PubMed

Favorable prognosis for patients 12 to 18 months of age with stage 4 nonamplified MYCN neuroblastoma: a Children's Cancer Group Study. J Clin Oncol. 2005 Sep 20; 23(27):6474-80. View in: PubMed

Enlarged and prominent nucleoli may be indicative of MYCN amplification: a study of neuroblastoma (Schwannian stroma-poor), undifferentiated/poorly differentiated subtype with high mitosis-karyorrhexis index. Cancer. 2005 Jan 1; 103(1):174-80. View in: PubMed

TrkA expression in peripheral neuroblastic tumors: prognostic significance and biological relevance. Cancer. 2004 Oct 15; 101(8):1873-81. View in: PubMed

GABAergic system gene expression predicts clinical outcome in patients with neuroblastoma. J Clin Oncol. 2004 Oct 15; 22(20):4127-34. View in: PubMed

Natural killer T cells infiltrate neuroblastomas expressing the chemokine CCL2. J Exp Med. 2004 May 3; 199(9):1213-21. View in: PubMed

Identification of genes that are regulated transcriptionally by Myc in childhood tumors. Cancer. 2003 Aug 15; 98(4):841-53. View in: PubMed

Impact of radiotherapy for high-risk neuroblastoma: a Children's Cancer Group study. Int J Radiat Oncol Biol Phys. 2003 May 1; 56(1):28-39. View in: PubMed

Antidisialoganglioside/granulocyte macrophage-colony-stimulating factor fusion protein facilitates neutrophil antibody-dependent cellular cytotoxicity and depends on FcgammaRII (CD32) and Mac-1 (CD11b/CD18) for enhanced effector cell adhesion and azurophil granule exocytosis. Blood. 2002 Jun 1; 99(11):4166-73. View in: PubMed

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