I’m a pediatric oncologist with both clinical and research responsibilities. On the clinical side, I have developed expertise in the management of patients with neuroblastoma, germ cell tumors, and histiocytic diseases (such as Langerhans cell histiocytosis and hemophagocytic lymphohistiocytosis, or LCH and HLH). I help coordinate the care of children with these diseases at Children's Hospital, and have roles in the international community in developing clinical and translational programs for neuroblastoma and histiocytic diseases. This involves leadership roles within the Children’s Oncology Group (COG), the International Neuroblastoma Risk Group (INRG), and the International Histiocyte Society.
In the laboratory, I'm involved in neuroblastoma research, an interest initially developed while training with Dr. Garrett Brodeur here at Children’s Hospital. Dr. Brodeur is a world renowned researcher studying the molecular pathogenesis of this tumor. He piqued my interest in neuroblastoma and I continue to study it even after transitioning to my own independent laboratory. My lab currently focuses on defining the cancer pathways that support neuroblastoma development, particularly those that interact with the MYCN gene, and in developing novel therapeutics that might target this disease.
Neuroblasts are the immature cells that will eventually develop into the adrenal glands and peripheral nerve tissues of a child. When these cells fail to mature properly, they may instead become cancerous -- giving rise to neuroblastoma. My laboratory studies the behavior of such neuroblastoma cells, what distinguishes them from their normal counterparts, and what facets of their behavior might be exploited by novel treatments. Surprisingly, many of the genetic changes that occur in cancer cells to make them very aggressive also provide certain vulnerabilities that can be exploited once they are understood.
Currently, we have several major laboratory projects underway. First, we are studying how MYC genes regulate polyamines, and how amplification of the MYCN gene (which is found in about 25 percent of tumors and is associated with a very aggressive tumor) causes a tumor to be dependent on polyamines. We’ve discovered that numerous medications that interfere with steps in the pathway of making polyamines can disrupt neuroblastomas -- either blocking them before they form, or making tumors regress or respond more fully to standard therapies. These novel approaches have been validated in complementary models of neuroblastoma in mice and will also be studied in children with relapsed high-risk disease.
We also are studying the process by which neuroblastoma cells become resistant to the body’s protective mechanisms to prevent them from becoming cancerous, and ultimately how these cells become resistant to the chemotherapy and radiation therapy used to kill them. A large part of this process is overseen by proteins of the Bcl2 family. Our laboratory has been defining the patterns of Bcl2 proteins that cause poor treatment response. We’ve also been studying diverse small molecule drugs that interfere with those functions of the Bcl2 family that keep cancer cells alive. These studies are designed to both improve the initial response of these tumors to chemotherapy, and also to restore therapy responses in tumors cells that have become resistant and relapsed.
These two areas of study have been rewarding because not only do they help us better understand the biology underlying this cancer type and its distinct behaviors, but because each of these areas is leading directly into new therapies. We anticipate that drugs in both of these classes will soon be tested in clinical trials to see if they improve the outcome of children with advanced neuroblastoma.
One of the things that makes our neuroblastoma program at Children's Hospital unique is the depth and breath of our team – from basic research to the translation of novel discoveries to new therapies that improve outcomes. We have the ability to translate the gap from bedside to bench and provide the most effective treatments now and for the future.
- Education and Training
Columbia University College of Physicians and Surgeons (MD), New York, NY
Pediatrics - Children's Memorial Hospital/Northwestern University, Chicago, IL
Pediatric Hematology/Oncology - The Children's Hospital of Philadelphia, Philadelphia, PA
- Titles and Academic Titles
Associate Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania
- Centers and Programs
- Research Interests
Hogarty MD, Brodeur GM. Neuroblastoma. In: Arceci R, editor. Rudolph's pediatrics. 22nd ed. New York: McGraw-Hill Professional; 2011.
Brodeur GM, Hogarty MD, Mosse YP, Maris JM. Neuroblastoma. In: Pizzo PA, Poplack DG, editors. Principles and practice of pediatric oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins, Inc.; 2010.
Hogarty MD, Shusterman S, Evans A. Wilms tumor. In: Brodeur GM, Manno CS, editors. Pediatric hematology/oncology: requisites in pediatrics. Philadelphia: CV-Mosby; 2009.
Goldsmith KC, Hogarty MD, Nichols K. The childhood histiocytoses: Langerhans cell histiocytosis and hemophagocytic lymphohistiocytosis. In: Brodeur GM, Manno CS, editors. Pediatric hematology/oncology: requisites in pediatrics. Philadelphia: CV-Mosby; 2009.
Hogarty MD, Brodeur GM. Gene amplification in human cancers: biological and clinical significance. In: Vogelstein B, Kinzler KW, editors. The genetic basis of human cancer. 2nd ed. New York: McGraw-Hill; 2002. p. 115-58.
Caron HN, Hogarty MD. Imprinting of 1p, MYCN, and other loci in neuroblastoma. In: Brodeur GM, Sawada T, Tsuchida Y, Voute PA, editors. Neuroblastoma. Philadelphia: Elsevier Science; 2000. p. 101-12.
Hogarty MD, Lange B. Oncologic emergencies. In: Fleisher GR, Ludwig S, editors. Textbook of pediatric emergency medicine. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2000. p. 1157-90.
Hogarty MD. Neuroblastoma. In: Altschuler SM, Ludwig S, editors. Pediatrics at a glance. Philadelphia: Current Medicine, Inc. and Appleton & Lange; 1998. p. 218-9.
Hogarty MD. Wilms tumor. In: Altschuler SM, Ludwig S, editors. Pediatrics at a glance. Philadelphia: Current Medicine, Inc. and Appleton & Lange; 1998. p. 320-1.
Hogarty MD. Hodgkins disease. In: Altschuler SM, Ludwig S, editors. Pediatrics at a glance. Philadelphia: Current Medicine, Inc. and Appleton & Lange; 1998. p. 154-5.
Hogarty MD. Immune thrombocytopenic purpura. In: Schwartz MW, editor. The CHOP 5-minute pediatric consult. Baltimore: Williams & Wilkins; 1996.
Hogarty MD. Glucose-6-phosphate dehydrogenase deficiency. In: Schwartz MW, editor. The CHOP 5-minute pediatric consult. Baltimore: Williams & Wilkins; 1996.
Hogarty MD. Retinoblastoma. In: Schwartz MW, editor. The CHOP 5-minute pediatric consult. Baltimore: Williams & Wilkins; 1996.
Hogarty, MD. IL-17A in LCH: systemic biomarker, local factor, or none of the above? Mol Ther. 2011 Aug; 19(8):1405-6. doi: 10.1038/mt.2011.150. Cited in PubMed: PMID 21804617. Read the abstract
Shields CL, Hogarty MD, Kligman BE, Christian C, Ehya H, Shields JA. Langerhans cell histiocytosis of the uvea with neovascular glaucoma: diagnosis by fine-needle aspiration biopsy and management with intraocular bevacizumab and brachytherapy. J AAPOS. 2010 Dec;14(6):534-7. Cited in PubMed: PMID 21168078. Read the abstract
Hogarty MD. Mcl1 becomes ubiquitin-ous: new opportunities to antagonize a pro-survival protein. Cell Res. 2010 Apr;20(4):391-3. Cited in PubMed: PMID 20357805. No abstract available.
Goldsmith KC, Lestini BJ, Gross M, Ip L, Bhumbla A, Zhang X, et al. BH3 response profiles from neuroblastoma mitochondria predict activity of small molecule Bcl-2 family antagonists. Cell Death Differ. 2010; 17:872-882. Cited in PubMed; PMID: 19893570. Read the abstract
Vermeulen J, De Preter K, Naranjo A, Vercruysse L, Van Roy N, Hellemans J, et al. Predicting outcomes for children with neuroblastoma using a multigene-expression signature: a retrospective SIOPEN/COG/GPOH study. Lancet Oncol. 2009;10:663-670. Cited in PubMed; PMID: 19515614. Read the article
Goldsmith KC, Hogarty MD. Small molecule BH3 mimetics to antagonize Bcl2-homologue survival functions in cancer. Curr Opin Investig Drugs. 2009; 10 (6): 559-571. Cited in PubMed;PMID: 19513945. Read the abstract
Evageliou NF, Hogarty MD. Molecular pathways: disrupting polyamine homeostasis as a therapeutic strategy for neuroblastoma. Clin Cancer Res. 2009;15 (19): 5956-61. Cited in PubMed; PMID: 19789308. Read the article
Lestini BJ, Goldsmith KC, Fluchel MN, Liu X, Chen NL, Goyal B, et al. Mcl1 downregulation sensitizes neuroblastoma to cytotoxic chemotherapy and small molecule Bcl2-family antagonists. Cancer Biol Ther. 2009; 8(16): 1587-95. Cited in PubMed; PMID: 19556859. Read the abstract
Chayka O, Corvetta D, Dews M, Caccamo AE, Piotrowska I, Santilli G, et al. Clusterin, a haploinsufficient tumor suppressor gene in neuroblastomas. J Natl Cancer Inst. 2009;101:663-77. Cited in PubMed; PMID: 19401549. Read the article
Okamatsu C, London WB, Naranjo A, Hogarty MD, Gastier-Foster JM, Look AT, et al. Clinicopathological characteristics of ganglioneuroma and ganglioneuroblastoma: a report from the CCG and COG. Pediatr Blood Cancer. 2009; 53: 563-69. Cited in PubMed; PMID: 19301388. Read the article
Combaret V, Hogarty MD, London W, McGrady P, Iacono I, Brejon S, et al. Influence of neuroblastoma stage on serum-based detection of MYCN amplification. Pediatr Blood Cancer. 2009;53(3):329-31.Cited in PubMed; PMID: 19301388. Read the article
Posters and Presentations
Hogarty MD. Polyamine inhibition blocks initiation and progression of neuroblastoma [presentation]. Advances in Neuroblastoma Research; 2010 Jun 22; Stockholm, Sweden.
Hogarty MD. Bc12 family proteins, chemoresistance, and apoptosis-directed therapies for neuroblastoma [invited lecture]. Program in Cell Biology Seminar, The Hospital for Sick Children, University of Toronto; 2010 Mar 19; Toronto, CA.
Hogarty MD. Genetic alterations in neuroblastoma and their clinical utility [invited lecture]. Medical Genetics I (GC550), Arcadia University; 2009 Dec 10; Philadelphia, PA.
Hogarty MD. Polyamine depletion as a therapeutic strategy for MYC-driven embryonal tumors [invited lecture]. Aflac Cancer Center Visiting Professor Seminar, Children's Healthcare of Atlanta; 2009 Jun 4; Atlanta, GA.
Hogarty MD. Polyamine dependence in neuroblastoma: a novel therapeutic opportunity [invited lecture]. Visiting Professor Research Seminar, Vanderbilt-Ingram Cancer Center, Vanderbilt University; 2009 Apr 6; Nashville, TN.
- Editorial and Academic Positions
Ad hoc reviewer
Archives of Pediatric and Adolescent Medicine
Biochimica et Biophysica Acta -- Gene Structure and Function
Cancer Epidemiology, Biomarkers & Prevention
Clinical Cancer Research
Genes Chromosomes & Cancer
Journal of Cellular Biochemistry
Journal of Clinical Investigation
Journal of Clinical Oncology
Medical and Pediatric Oncology
Pediatric Blood and Cancer
Pediatric and Developmental Pathology
Pediatric Emergency Medicine
The American Journal of Pathology
The FASEB Journal
2009, Member, Search Committee for Pediatric Oncology Survivorship Faculty Member
2008-present, Co-chair, Pediatric Protocol Review Committee, Division of Oncology and Abramson Family Cancer Center
2008-present, Resident Physician-Scientist Mentor Committee
- Editorial and Academic Positions