Faculty

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Michael D. Hogarty, MD

Professor of Pediatrics (Oncology) at the Children's Hospital of Philadelphia

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Department: Pediatrics

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1f Graduate Group Affiliations 8

Cell and Molecular Biology

46 Contact information
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Division of Oncology
2f The Children's Hospital of Philadelphia
39 Colket Translational Research Building, Room 3020
43 3501 Civic Center Boulevard
Philadelphia, PA 19104-4318

2e Office: 215-590-3931
32 Fax: 215-590-3770
32 Lab: 215-590-9930
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Email:
hogartym@chop.edu

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13 Education:
21 b B.E.S. 23 (Biomedical Engineering) c
40 Johns Hopkins University, Baltimore, MD, 1986.
21 9 M.D. 15 (Medicine) c
5d Columbia University College of Physicians and Surgeons, New York, NY, 1990.
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Links
77 CCCR Investigator Profile
88 CHOP Research Institute Faculty Profile
7a CCCR Laboratory Profile
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5 3 3 8f Permanent link
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b6 > Perelman School of Medicine > Faculty > Details a

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Description of Research Expertise

b6 The Hogarty Lab studies the childhood solid tumor neuroblastoma with the goal of identifying principal oncogenic pathways for the development of novel therapeutics.
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84 Keywords: pediatric cancer, neuroblastoma, MYC, Bcl2 signaling, cancer therapy resistance, polyamines, oncogenic translation
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fe There are currently two main projects within the lab focused on (1) the contributions of polyamines to neuroblastoma pathogenesis; and (2) the role Bcl2 family proteins and mitochondria play in defining stress sensitivity and resistance patterns.
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1f9 Current polyamine-related efforts utilize targeted inhibitors of polyamine metabolism to credential polyamine homeostasis as an essential signaling module downstream of MYC. We use complementary preclinical models (human xenografts/PDXs and transgenic mouse models) to define the extent of cancer cell intrinsic (protein stress) and extrinsic (altered tumor immuno-environment) activities. We have made fundamental discoveries related to the role of polyamines in support of oncogenic translation.
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1b0 Our Bcl2 functional profiling studies have led to the recognition of heterogeneity in major survival dependencies for neuroblastoma that appear hardwired in tumors although adaptations in Bcl2 signaling arise in response to therapeutic pressure. We are developing biomarkers to triage selective Bcl2 family inhibitors. Importantly, we have identified a mitochondrial phenotype for multidrug resistance using these approaches.
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Description of Clinical Expertise

258 Dr. Hogarty has clinical expertise managing patients with neuroblastoma and histiocytic diseases of childhood (LCH and JXG). He holds international leadership roles in neuroblastoma clinical and translational research through the Children's Oncology Group (COG), Advances in Neuroblastoma Research Association (ANRA), International Neuroblastoma Research Group (INRG) and the New Approaches to Neuroblastoma Therapy Consortium (NANT). He also participates in the International Histiocyte Society and is a co-investigator and site PI for the North America Consortium for Histiocytosis.
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Selected Publications

17e Sausen M, Leary RJ, Jones S, Wu J, Reynolds CP, Liu X, Blackford A, Parmigiani G, Diaz Jr LA, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE, Hogarty MD. : Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma. Nature Genetics 45(1): 12-7, Jan 2012.

324 Pugh TJ, Morozova O, Attiyeh A, Asgharzadeh S, Wei JS, Auclair D, Carter, Cibulskis K, Hanna M, Kiezun A, Kim J, Lawrence MS, Lichenstein L, McKenna A, Pedamallu CS, Ramos AH, Shefler E, Sivachenko A, Sougnez C, Stewart C, Ally A, Birol I, Chiu R, Corbett RD, Hirst M, Jackman SD, Kamoh B, Khodabakshi AH, Krzywinski M, Lo A, Moore RA, Mungall KL, Qian J, Tam A, Thiessen N, Zhao Y, Cole KA, Diamond M, Diskin SJ, Mosse YP, Wood AC, Ji L, Sposto R, Badgett T, London WB, Moyer Y, Gastier-Foster JM, Smith MA, Guidry Auvil JM, Gerhard DS, Hogarty MD, Jones SJM, Lander ES, Gabriel SB, Getz G, Seeger RC, Khan J, Marra MA, Meyerson M, Maris JM.: The genetic landscape of high-risk neuroblastoma. Nature Genetics 45(3): 279-284, 2013.

115 Laetsch TW, Liu X, Vu A, Sliozberg M, Vido M, Elci OU, Goldsmith KC, Hogarty MD.: Multiple components of the spliceosome regulate Mcl1 activity in neuroblastoma. Cell Death and Disease 20(5): e1072, 2014.

143 Goldsmith KC, Gross M, Pierce S, Luyindula D, Liu X, Vu A, Sliozberg M, Guo R, Zhao H, Reynolds CP, Hogarty MD. : Mitochondrial Bcl-2 family dynamics define therapy response and resistance in neuroblastoma. Cancer Research 72(10): 2565-77, May 2012.

14a Goldsmith K C, Lestini B J, Gross M, Ip L, Bhumbla A, Zhang X, Zhao H, Liu X, Hogarty M D: BH3 response profiles from neuroblastoma mitochondria predict activity of small molecule Bcl-2 family antagonists. Cell Death and Differentiation 17(5): 872-82, 2010.

142 Lestini BJ, Goldsmith KC, Fluchel MN, Liu X, Chen NL, Goyal B, Pawel BR, Hogarty MD.: Mcl1 downregulation sensitizes neuroblastoma to cytotoxic chemotherapy and small molecule Bcl2-family antagonists. Cancer Biology & Therapy 8(16): 1587-1595, 2009.

1ad Hogarty MD, Norris MD, Davis K, Liu X, Evageliou NF, Hayes CS, Pawel B, Guo R, Zhao H, Sekyere E, Keating J, Thomas W, Cheng NC, Murray J, Smith J, Sutton R, Venn N, London WB, Buxton A, Gilmour SK, Marshall GM, Haber M.: ODC1 is a critical determinant of MYCN oncogenesis and a therapeutic target in neuroblastoma. Cancer Research 68(23): 9735-9745, 2008.

362 Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Choti MA, Clarence LC, Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff M, Hong S, Jiao Y, Juhl HH, Kim JJ, Siravegna G, Laheru DA, Lauricella C, Lim M, Lipson EJ, Marie S, Netto GJ, Oliner KS, Olivi A, Olsson L, Riggins GJ, Sartore-Bianchi A, Schmidt K, Shih L, Shinjo S, Siena S, Theodorescu D, Tie J, Hawkins TT, Veronese S, Wang T, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, and Diaz LA, Jr.: Detection of circulating tumor DNA in early- and late-stage human malignancies. Science Translational Medicine 6(224): 224, 2014.

18a Bresler SC, Weiser DA, Huwe PJ, Park JH, Krytska K, Ryles H, Laudenslager M, Rappaport EF, Wood AC, McGrady PW, Hogarty MD, London WB, Radhakrishna R, Lemmon MA, Mosse YP.: ALK mutations confer differential oncogenic activation and sensitivity to ALK inhibition therapy in neuroblastoma. Cancer Cell 26(5): 682-694, 2014.

12e Qing G, Li B, Vu A, Skuli N, Walton ZE, Liu X, Mayes PA, Wise DR, Thompson CB, Maris JM, Hogarty MD, Simon MC.: ATF4 regulates MYC-mediated neuroblastoma cell death upon glutamine deprivation. Cancer Cell 22(5): 631-44, Nov 2012.

131 Evageliou NF, Haber M, Vu A, Laetsch TW, Murray J, Gamble L, Cheng NC, Liu K, Reese M, Corrigan KA, Ziegler DS, Webber H, Hayes CS, Pawel B, Marshall GM, Zhao H, Gilmour SK, Norris MD, and Hogarty MD.: Polyamine antagonist therapies inhibit neuroblastoma 65 initiation and progression. Clinical Cancer Research 22(17): 4391-4404, 2016.

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