Garrett M. Brodeur, MD

Garrett M. Brodeur, MD

Garrett M. Brodeur, MD, is the Director of the Cancer Predisposition Program at CHOP and Associate Director of the Abramson Cancer Center at Penn. He has a special interest in the molecular biology, genetics and targeted therapy of neuroblastoma.

Areas of Expertise: Neuroblastoma, Cancer predisposition, Targeted cancer therapy, Nanoparticle drug delivery
Locations: Main Campus
Appointments and Referrals: 1-800-TRY-CHOP (1-800-879-2467)

Background

Garrett M. Brodeur, MD, is associate chair for Research in Pediatrics, as well as professor of Pediatrics at the University of Pennsylvania and adjunct professor at The Wistar Institute in Philadelphia.

Dr. Brodeur is a graduate of the Washington University School of Medicine in St. Louis, Missouri, where he completed his pediatric residency. He continued his specialty training with a fellowship in pediatric hematology-oncology at St. Jude’s Children’s Research Hospital in Memphis. He  returned to Washington University for a post-doctoral fellowship in molecular genetics in 1981, and he joined the faculty at CHOP in 1993.

Dr. Brodeur maintains a special interest in the biology, genetics and treatment of neuroblastoma, the most common solid tumor in childhood, and is internationally recognized for his work in this area. He is currently studying certain genes, proteins and pathways that play important roles in the development and progression of neuroblastomas. For example, he is looking for a tumor suppressor gene on the short arm of chromosome 1 that is frequently deleted or inactivated in aggressive neuroblastomas. He is also examining the role that TRK (pronounced “track”) receptors play in these tumors. TRK-A is expressed on the surface of favorable neuroblastomas that are prone to regress, differentiate or respond well to modest treatment. TRK-B is expressed on the more aggressive neuroblastomas, particularly those that also amplify the MYCN proto-oncogene (a very high risk feature). Finally, he is evaluating a novel drug that can block the function of either TRK-A or TRK-B, and this causes cells expressing these receptors to die by a cellular “suicide”.

Recently, he has been invited to give lectures on his work at the National Institutes of Health/National Cancer Institute in Bethesda, Maryland; at Kyushu University in Japan, at Washington University in St. Louis, Missouri, and at Memorial Sloan-Kettering Cancer Center in New York City.

He is the author of more than 160 papers and has contributed numerous textbook chapters on topics related to the biological and clinical significance of genetic changes in neuroblastomas. Dr. Brodeur is also the principal investigator or co- investigator of six NIH/NCI grants studying the genetic basis of neuroblastomas.

Education and Training

Medical School

MD -Washington University School of Medicine, St. Louis, MO

Internship

Pediatrics - St. Louis Children's Hospital, St. Louis, MO

Residency

Pediatrics - St. Louis Children's Hospital, St. Louis, MO

Fellowship

Pediatric Hematology-Oncology - St. Jude Children's Research Center, Memphis, TN
Postdoctoral fellowship in Molecular Genetics - Washington University School of Medicine, St. Louis, MO

Board Certification

Pediatric Hematology-Oncology
Pediatrics

Titles and Academic Titles

Director, Cancer Predisposition Program

Chair, Pediatric Research Advisory Committee

Associate Director for Pediatric Research, Abramson Cancer Center

Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania

Conditions Treated

Departments and Services

Research Interests

Molecular biology and genetics of human neuroblastoma and genetics of childhood cancer

Publications

Papers

2016

Iyer R, Wehrmann L, Golden RL, Naraparaju K, Croucher JL, MacFarland SP, Guan P, Kolla V, Wei G, Cam N, Li G, Hornby Z, Brodeur GM. Entrectinib is a potent inhibitor of Trk-driven neuroblastomas in a xenograft mouse model. Cancer Lett. 2016 Mar 28;372(2):179-86. doi: 10.1016/j.canlet.2016.01.018. Epub 2016 Jn 18.

Naraparaju K, Kolla V, Zhuang T, Higashi M, Iyer R, Kolla S, Okawa ER, Blobel GA, Brodeur GM. Role of microRNAs in epigenetic silencing of the CHD5 tumor suppressor gene in neuroblastomas. Oncotarget. 2016 Feb 16.

2015

Thompson D, Vo KT, London WB, Fischer M, Ambros PF, Nakagawara A, Brodeur GM, Matthay KK, DuBois SG. Identification of patient subgroups with markedly disparate rates of MYCN amplification in neuroblastoma: A report from the International Neuroblastoma Risk Group project.

Higashi M, Kolla V, Iyer R, Naraparaju K, Zhuang T, Kolla S, Brodeur GM. Retinoic acid-induced CHD5 upregulation and neuronal differentiation of neuroblastoma. Mol Cancer. 2015 Aug 7;14:150. doi: 10.1186/s12943-015-0425-y.

Kolla V, Naraparaju K, Zhuang T, Higashi M, Kolla S, Blobel GA, Brodeur GM. The tumour suppressor CHD5 forms a NuRD-type chromatin remodeling complex. Biochem J. 2015 Jun 1;468(2):345-52. doi: 10.1042/BJ20150030.

Alferiev IS, Iyer R, Croucher JL, Adamo RF, Zhang K, Mangino JL, Kolla V, Fishbein I, Brodeur GM, Levy RJ, Chorny M. Nanoparticle-mediated delivery of a rapidly activatable prodrug of SN-38 for neuroblastoma therapy. Biomaterials. 2015 May;51:22-9. doi: 10.1016/j.biomaterials.2015.01.075. Epub 2015 Feb 16.

Iyer R, Croucher JL, Chorny M, Mangino JL, Alferiev IS, Levy RJ, Kolla V, Brodeur GM. Nanoparticle delivery of an SN38 conjugate is more effective than irinotecan in a mouse model of neuroblastoma. Cancer Lett. 2015 May 1;360(2):205-12. doi: 10.1016/j.canlet.2015.02.011. Epub 2015 Feb 12.

2014

Croucher JL, Iyer R, Li N, Molteni V, Loren J, Gordon WP, Tuntland T, Liu B, Brodeur GM. TrkB inhibition by GNF-4256 slows growth and enhances chemotherapeutic efficacy in neuroblastoma xenografts. Cancer Chemother Pharmacol. 2015 Jan;75(1):131-41. doi: 10.1007/s00280-014-2627-1. Epub 2014 Nov 14.

Brodeur GM, Bagatell R. Mechanisms of neuroblastoma regression. Nat Rev Clin Oncol. 2014 Dec;11(12):704-13. doi: 10.1038/nrclinonc.2014.168. Epub 2014 Oct 21.

Werner P, Paluru P, Simpson AM, Latney B, Iyer R, Brodeur GM, Goldmuntz E. Mutations in NTRK3 suggest a novel signaling pathway in human congenital heart disease. Hum Mutat. 2014 Dec;35(12):1459-68. doi: 10.1002/humu.22688. Epub 2014 Nov 7.

Redden RA, Iyer R, Brodeur GM, Doolin EJ. Rotary bioreactor culture can discern specific behavior phenotypes in Trk-null and Trk-expressing neuroblastoma cell lines. In Vitro Cell Dev Biol Anim. 2014 Mar;50(3):188-93. doi: 10.1007/s11626-013-9716-z.

Kolla V, Zhuang T, Higashi M, Naraparaju K, Brodeur GM. Role of CHD5 in human cancers: 10 years later. Cancer Res. 2014 Feb 1;74(3):652-8. doi: 10.1158/0008-5472.CAN-13-3056. Epub 2014 Jan 13.

Brodeur GM, Iyer R, Croucher JL, Zhuang T, Higashi M, Kolla V. Therapeutic targets for neuroblastomas. Expert Opin Ther Targets. 2014 Mar;18(3):277-92. doi: 10.1517/14728222.2014.867946. Epub 2014 Jan 6.

Editorial and Academic Positions

Editorial positions

Editorial boards

1990-present, Cancer and Metastasis Reviews
1989-present, Genes, Chromosomes and Cancer
1987-present, Medical and Pediatric Oncology
1982-present, Cancer Genetics and Cytogenetics

Academic positions

Pediatric Oncology Tumor Board: Neuroblastoma, August 2005

Cancer Pharmacology Course (PHRM 560), U. Penn, Tyrosine kinases as targets for future therapy, February 2006