Jeffrey A. Toretsky

ORCID: 0000-0003-3619-2879
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About
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Research Areas
  • Sarcoma Diagnosis and Treatment
  • Neuroblastoma Research and Treatments
  • Protein Degradation and Inhibitors
  • RNA modifications and cancer
  • RNA Research and Splicing
  • FOXO transcription factor regulation
  • Multiple Myeloma Research and Treatments
  • Ubiquitin and proteasome pathways
  • Lymphoma Diagnosis and Treatment
  • Peptidase Inhibition and Analysis
  • PARP inhibition in cancer therapy
  • Cancer-related gene regulation
  • Radiopharmaceutical Chemistry and Applications
  • interferon and immune responses
  • Retinoids in leukemia and cellular processes
  • CAR-T cell therapy research
  • Virus-based gene therapy research
  • Neurofibromatosis and Schwannoma Cases
  • Signaling Pathways in Disease
  • Monoclonal and Polyclonal Antibodies Research
  • Cancer Genomics and Diagnostics
  • Cancer, Hypoxia, and Metabolism
  • RNA regulation and disease
  • Acute Myeloid Leukemia Research
  • RNA Interference and Gene Delivery

Georgetown University
2016-2025

Georgetown University Medical Center
2015-2025

Georgetown Lombardi Comprehensive Cancer Center
2011-2025

Weatherford College
2024

Vince Lombardi Cancer Clinic
2006-2023

Indiana University – Purdue University Indianapolis
2010-2023

Indiana University School of Medicine
2010-2023

MedStar Georgetown University Hospital
2021-2022

Emory University
2015

Memorial Sloan Kettering Cancer Center
2001-2013

Most cancer cells are characterized by aneuploidy, an abnormal number of chromosomes. We have identified a clue to the mechanistic origins aneuploidy through integrative genomic analyses human tumors. A diverse range tumor types were found harbor deletions or inactivating mutations STAG2, gene encoding subunit cohesin complex, which regulates separation sister chromatids during cell division. Because STAG2 is on X chromosome, its inactivation requires only single mutational event. Studying...

10.1126/science.1203619 article EN Science 2011-08-18

Purpose A balanced chromosomal translocation, t(15;19), resulting in the BRD4-NUT oncogene, has been identified a lethal carcinoma of young people, disease described primarily case reports. We sought to amass more definitive series tumors with NUT and/or BRD4 gene rearrangements and determine distinct clinicopathologic features. Patients Methods Carcinomas (N = 98) individuals (median age, 32.5 years) were screened for using dual-color fluorescence situ hybridization. Four published...

10.1200/jco.2004.02.107 article EN Journal of Clinical Oncology 2004-10-13

The Hedgehog (Hh) pathway is activated in some human cancers, including medulloblastoma. glioma-associated oncogene homolog (GLI) transcription factors are critical mediators of the Hh pathway, and their expression may be elevated tumors independent upstream signaling. Thus, therapies targeting GLI benefit a wide spectrum patients with mutations at different nodal points pathway. In this study, we present evidence that arsenic trioxide (ATO) suppresses cancer cell growth tumor development...

10.1172/jci42874 article EN Journal of Clinical Investigation 2010-12-23

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates and frequently carries oncogenic KRAS mutation. However, has thus far not been a viable therapeutic target. We found that the abundance of YAP mRNA, which encodes Yes-associated protein (YAP), regulated by Hippo pathway during tissue development homeostasis, was increased in human PDAC compared normal pancreatic epithelia. In genetically engineered Kras(G12D) Kras(G12D):Trp53(R172H) mouse models,...

10.1126/scisignal.2005049 article EN Science Signaling 2014-05-06

The p53 mutant, 143ala, was translated in vitro either rabbit reticulocyte lysate (RRL) or wheat germ extract (WGE). In RRL, p53-143ala protein of both mutant and wild-type conformation, as detected immunologically with conformation-specific antibodies, translated. chaperone HSP90, present found to coprecipitate only the mutated conformation p53. Geldanamycin, shown previously bind HSP90 destabilize its association other proteins, decreased amount detectable increased protein, without...

10.1073/pnas.93.16.8379 article EN Proceedings of the National Academy of Sciences 1996-08-06

Ewing's family of tumors is characterized by a well described reciprocal translocation, t(11;22)(q24;q12), which produces fusion protein (EWS/FLI-1) that transforms mouse fibroblasts. The EWS/FLI-1 has been shown to act as potent chimeric transcription factor. Overexpression insulin-like growth factor-I receptor (IGF-IR) implicated in many tumor models playing role cell and tumorigenesis. In addition, blockade the IGF-IR inhibits cells. Therefore, we first studied whether presence required...

10.1074/jbc.272.49.30822 article EN cc-by Journal of Biological Chemistry 1997-12-01

Ewing sarcoma family of tumors (ESFT) is an undifferentiated neoplasm the bone and soft tissue. ESFT characterized by a specific chromosomal translocation occurring between chromosome 22 (in most cases) 11, which generates aberrant transcription factor, EWS-FLI1. The function EWS-FLI1 essential for maintenance cell survival tumorigenesis. Hedgehog pathway activated in several cancers. Oncogenic potential mediated increasing activity GLI factors. Recent evidence suggests that increases...

10.1074/jbc.m806233200 article EN cc-by Journal of Biological Chemistry 2009-02-04

Looping together genes in cancer A subset of human cancers are characterized by aberrant fusion two specific genes. In some cases, the activity resultant protein drives tumor growth. Most appear to arise from simple reciprocal chromosomal translocations. Anderson et al. found that characteristic gene a bone and soft tissue called Ewing sarcoma is produced far more complicated mechanism (see Perspective Imielinski Ladanyi). nearly half tumors examined, was created formation dramatic genomic...

10.1126/science.aam8419 article EN Science 2018-08-30

Background Cancer stem cells are a chemotherapy-resistant population capable of self-renewal and regenerating the bulk tumor, thereby causing relapse patient death. Ewing's sarcoma, second most common form bone tumor in adolescents young adults, follows clinical pattern consistent with Stem Cell model – remission is easily achieved, even for patients metastatic disease, but remains frequent usually fatal. Methodology/Principal Findings We have isolated subpopulation sarcoma cells, from both...

10.1371/journal.pone.0013943 article EN cc-by PLoS ONE 2010-11-11

Significance Alternative splicing of RNA allows a limited number coding regions in the human genome to produce proteins with diverse functionality. has also been implicated as an oncogenic process. Identifying aspects cancer cells that differentiate them from noncancer remains ongoing challenge, and our research suggests alternatively spliced mRNA subsequent protein isoforms will provide new anticancer targets. We determined key oncoprotein Ewing sarcoma (ES), EWS-FLI1, regulates alternative...

10.1073/pnas.1500536112 article EN Proceedings of the National Academy of Sciences 2015-03-03

// Tsion Zewdu Minas 1,* , Didier Surdez 2,3,* Tahereh Javaheri 4,* Miwa Tanaka 5,* Michelle Howarth 6,* Hong-Jun Kang 7,* Jenny Han 1 Zhi-Yan 2,3 Barbara Sax 4 E. Kream 8 Sung-Hyeok Hong Haydar Çelik Franck Tirode Jan Tuckermann 9 Jeffrey A. Toretsky Lukas Kenner 4,10,15 Heinrich Kovar 12,13 Sean Lee 7 Alejandro Sweet-Cordero 6 Takuro Nakamura 5 Richard Moriggl 4,11,16 Olivier Delattre 2,3,14 and Aykut Üren Department of Oncology, Georgetown University Medical Center,...

10.18632/oncotarget.9388 article EN Oncotarget 2016-05-15

Introduction Insulin-like growth factor-II (IGF-II) is a regulatory peptide which critical for normal organismal and differentiation, implicated in tumor progression metastasis by variety of mechanisms, many otherwise unrelated tumors. IGF-II signaling pathways involve two specific receptors. A family six unique binding proteins exist, as well protein proteases which, turn, regulate IGF-II-binding levels. This report briefly describes the structural functional characteristics molecule...

10.1677/joe.0.1490367 article EN Journal of Endocrinology 1996-06-01

Abstract Cervical carcinoma, the second leading cause of cancer deaths in women worldwide, is associated with human papillomavirus (HPV). HPV-infected individuals are at high risk for developing cervical carcinoma; however, molecular mechanisms that lead to progression have not been established. We hypothesized a multistep carcinogenesis model, HPV provides initial hit and activation canonical Wnt pathway may serve as hit. To test this hypothesis, we evaluated promoting factor HPV-induced...

10.1158/0008-5472.can-05-0455 article EN Cancer Research 2005-07-15

Abstract Neuropeptide Y (NPY) is a sympathetic neurotransmitter recently found to be potently angiogenic and growth promoting for endothelial, vascular smooth muscle neuronal cells. NPY its cognate receptors, Y1, Y2 Y5, are expressed in neural crest–derived tumors; however, their role regulation of unknown. The effect on the vascularization neuroendocrine tumors was tested using three types cells: neuroblastoma, pheochromocytoma, Ewing's sarcoma family (ESFT). varied expression which linked...

10.1158/0008-5472.can-04-2192 article EN Cancer Research 2005-03-01
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