Faculty

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Anat Erdreich-Epstein, MD, PhD
Associate Professor of Pediatrics
Pediatrics
CHL Mail Stop 57 Off Campus Los Angeles
+1 323 361 4613

Overview

For more information please contact Dr. Anat Epstein, epstein@usc.edu

Our laboratory studies molecular mechanisms in brain cancer. Brain tumors are the most common cause of cancer-related death in children. Better cancer therapy can only come from improved understanding of the molecular mechanisms driving growth of tumors. We strive to understand the biology of brain tumors and thus contribute to development of better treatments based on their biology.

We were the first to show that PID1 (Phosphotyrosine Interaction Domain containing 1; also called NYGGF4), thought to be an inhibitor of insulin receptor signaling, is an inhibitor of growth of a number of brain cancer cell lines (Clinical Cancer Research 2014; PMID: 24300787). These include medulloblastoma (the most common malignant brain tumor in children), gliomas and atypical teratoid rhabdoid (ATRT) tumors. We also found that patients whose medulloblastoma or glioma tumors had higher PID1 mRNA had longer survival. This work was the first peer-reviewed publication to link PID1 to cancer and suggested that PID1 is a novel candidate tumor suppressor in brain cancers. More recently we showed that PID1 mediates some of the tumor-killing effect of chemotherapy, potentially explaining the link between longer survival and higher tumor levels of PID1 mRNA (Scientific Reports, 2017; PMID:28400607).

Overall, only little else is known about PID1 to date. PID1 has mostly been studied in adipocytes and muscle cells where it is considered an inhibitor of insulin receptor signaling and thought to play a role in insulin resistance in obesity. PID1 inhibits mitochondrial function and directly binds to the Low Density lipoprotein receptor-related Protein 1, LRP1, although the function of this interaction remains unknown. PID1 mRNA level is also altered in brains of Alzheimer’s patients compared to healthy brains, although here too, its function is not yet known.

Ongoing work in our lab suggests that PID1 plays a central role in a number of important biological processes. Our laboratory studies are now focused on understanding the function and molecular mechanism of PID1 in cancer using in vitro and in vivo approaches. These studies will also help understand the function of PID1 in other processes in health and disease and will guide development of improved therapies

Publications

PID1 increases chemotherapy-induced apoptosis in medulloblastoma and glioblastoma cells in a manner that involves NF?B. PID1 increases chemotherapy-induced apoptosis in medulloblastoma and glioblastoma cells in a manner that involves NF? B. Sci Rep. 2017 Apr 11; 7(1):835. View in: PubMed

Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors. Cancer Cell. 2016 Dec 12; 30(6):891-908. 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

CXCR4 increases in-vivo glioma perivascular invasion, and reduces radiation induced apoptosis: A genetic knockdown study. Oncotarget. 2016 Nov 11. View in: PubMed

Re-irradiation of Recurrent Pineal Germ Cell Tumors with Radiosurgery: Report of Two Cases and Review of Literature. Cureus. 2016; 8(4):e585. View in: PubMed

Molecular subgroups of medulloblastoma identification using noninvasive magnetic resonance spectroscopy. Neuro Oncol. 2016 Jan; 18(1):126-31. View in: PubMed

BarTeL, a Genetically Versatile, Bioluminescent and Granule Neuron Precursor-Targeted Mouse Model for Medulloblastoma. PLoS One. 2016; 11(6):e0156907. View in: PubMed

Wnt pathway in atypical teratoid rhabdoid tumors. Neuro Oncol. 2015 Apr; 17(4):526-35. View in: PubMed

Tumor-Associated Macrophages in SHH Subgroup of Medulloblastomas. Clin Cancer Res. 2015 Mar 15; 21(6):1457-65. View in: PubMed

Disrupting LIN28 in atypical teratoid rhabdoid tumors reveals the importance of the mitogen activated protein kinase pathway as a therapeutic target. Oncotarget. 2015 Feb 20; 6(5):3165-77. View in: PubMed

Pediatric brain tumor cell lines. J Cell Biochem. 2015 Feb; 116(2):218-24. View in: PubMed

The Chromatin-Modifying Protein HMGA2 Promotes Atypical Teratoid/Rhabdoid Cell Tumorigenicity. J Neuropathol Exp Neurol. 2015 Feb; 74(2):177-85. View in: PubMed

Disseminated Medulloblastoma in a Child with Germline BRCA2 6174delT Mutation and without Fanconi Anemia. Front Oncol. 2015; 5:191. View in: PubMed

Novel Paracrine Modulation of Notch-DLL4 Signaling by Fibulin-3 Promotes Angiogenesis in High-Grade Gliomas. Cancer Res. 2014 Oct 1; 74(19):5435-48. View in: PubMed

A retrospective analysis of recurrent intracranial ependymoma. Pediatr Blood Cancer. 2014 Jul; 61(7):1195-201. View in: PubMed

PID1 (NYGGF4), a New Growth-Inhibitory Gene in Embryonal Brain Tumors and Gliomas. Clin Cancer Res. 2014 Feb 15; 20(4):827-36. View in: PubMed

A novel tumor-promoting role for nuclear factor IA in glioblastomas is mediated through negative regulation of p53, p21, and PAI1. Neuro Oncol. 2014 Jan; 16(2):191-203. View in: PubMed

Heparanase-Induced GEF-H1 Signaling Regulates the Cytoskeletal Dynamics of Brain Metastatic Breast Cancer Cells. Mol Cancer Res. 2012 Jun; 10(6):689-702. View in: PubMed

Choroid plexus tumors; management, outcome, and association with the Li-Fraumeni syndrome: The Children's Hospital Los Angeles (CHLA) experience, 1991-2010. Pediatr Blood Cancer. 2012 Jun; 58(6):905-9. View in: PubMed

Novel cell lines established from pediatric brain tumors. J Neurooncol. 2012 Apr; 107(2):269-80. View in: PubMed

c-Abl Is an Upstream Regulator of Acid Sphingomyelinase in Apoptosis Induced by Inhibition of Integrins avß3 and avß5. PLoS One. 2012; 7(8):e42291. View in: PubMed

Microdeletion del(22)(q12. 2) encompassing the facial development-associated gene, MN1 (meningioma 1) in a child with Pierre-Robin sequence (including cleft palate) and neurofibromatosis 2 (NF2): a case report and review of the literature. BMC Med Genet. 2012; 13:19. View in: PubMed

Treatment of children with recurrent high grade gliomas with a bevacizumab containing regimen. J Neurooncol. 2011 Jul; 103(3):673-80. View in: PubMed

Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro. J Neuroinflammation. 2011; 8:162. 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

c-Abl mediates endothelial apoptosis induced by inhibition of integrins alphavbeta3 and alphavbeta5 and by disruption of actin. Blood. 2010 Apr 1; 115(13):2709-18. View in: PubMed

Nuclear factor IA is expressed in astrocytomas and is associated with improved survival. Neuro Oncol. 2010 Feb; 12(2):122-32. View in: PubMed

Metabolism of orthotopic mouse brain tumor models. Mol Imaging. 2009 Jul-Aug; 8(4):199-208. View in: PubMed

High-dose chemotherapy and autologous hematopoietic progenitor cell rescue in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors: the impact of prior radiotherapy on outcome. Cancer. 2009 Jul 1; 115(13):2956-63. View in: PubMed

Inducing a mode of NK-resistance to suppression by stress and surgery: a potential approach based on low dose of poly I-C to reduce postoperative cancer metastasis. Brain Behav Immun. 2007 May; 21(4):395-408. View in: PubMed

Progress in the treatment of childhood brain tumors: no room for complacency. Pediatr Hematol Oncol. 2007 Jan-Feb; 24(1):79-84. View in: PubMed

Androgen inducibility of Fgf8 in Shionogi carcinoma 115 cells correlates with an adjacent t(5;19) translocation. Genes Chromosomes Cancer. 2006 Feb; 45(2):169-81. View in: PubMed

Endothelial apoptosis induced by inhibition of integrins alphavbeta3 and alphavbeta5 involves ceramide metabolic pathways. Blood. 2005 Jun 1; 105(11):4353-61. View in: PubMed

Bone marrow mesenchymal stem cells provide an alternate pathway of osteoclast activation and bone destruction by cancer cells. Cancer Res. 2005 Feb 15; 65(4):1129-35. View in: PubMed

Approaches to treatment for extraocular retinoblastoma: Children's Hospital Los Angeles experience. J Pediatr Hematol Oncol. 2004 Jan; 26(1):31-4. View in: PubMed

Induction of intercellular adhesion molecule-1 on human brain endothelial cells by HIV-1 gp120: role of CD4 and chemokine coreceptors. Lab Invest. 2003 Dec; 83(12):1787-98. View in: PubMed

Placenta growth factor activates monocytes and correlates with sickle cell disease severity. Blood. 2003 Aug 15; 102(4):1506-14. View in: PubMed

Ceramide signaling in fenretinide-induced endothelial cell apoptosis. J Biol Chem. 2002 Dec 20; 277(51):49531-7. View in: PubMed

Successful multimodality therapy of recurrent multifocal juvenile granulosa cell tumor of the ovary. J Pediatr Hematol Oncol. 2002 Mar-Apr; 24(3):229-33. View in: PubMed

Plasminogen activator inhibitor-1 promotes angiogenesis by stimulating endothelial cell migration toward fibronectin. Cancer Res. 2001 Jul 15; 61(14):5587-94. View in: PubMed

Integrins alpha(v)beta3 and alpha(v)beta5 are expressed by endothelium of high-risk neuroblastoma and their inhibition is associated with increased endogenous ceramide. Cancer Res. 2000 Feb 1; 60(3):712-21. View in: PubMed

High affinity IgG receptor activation of Src family kinases is required for modulation of the Shc-Grb2-Sos complex and the downstream activation of the nicotinamide adenine dinucleotide phosphate (reduced) oxidase. J Immunol. 1999 Dec 1; 163(11):6023-34. View in: PubMed

Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages. J Leukoc Biol. 1999 Apr; 65(4):523-34. View in: PubMed

Characterization of Cbl-Nck and Nck-Pak1 interactions in myeloid FcgammaRII signaling. Exp Cell Res. 1998 Dec 15; 245(2):330-42. View in: PubMed

Differential expression of Wnt genes in normal and flat variants of PC12 cells, a cell line responsive to ectopic Wnt1 expression. Growth Factors. 1998; 15(2):149-58. View in: PubMed

Protein tyrosine phosphatase inhibitors in Fc gamma RI-induced myeloid oxidant signaling. Exp Cell Res. 1997 Dec 15; 237(2):288-95. View in: PubMed

Prolonged clinical response to vincristine treatment in two patients with idiopathic hypereosinophilic syndrome. Am J Pediatr Hematol Oncol. 1992 Nov; 14(4):348-51. View in: PubMed

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