Michael D. Hogarty

faculty photo
Associate Professor of Pediatrics at the Children's Hospital of Philadelphia
Member, Abramson Cancer Center
Assistant Member, The Children's Hospital of Philadelphia Research Institute
Member, Institute for Translational Medicine and Therapeutics, University of Pennsylvania
Director, Physician Scientist Program, The Children's Hospital of Philadelphia
Department: Pediatrics

Contact information
Division of Oncology
The Children's Hospital of Philadelphia
Colket Translational Research Building, Room 3020
3501 Civic Center Boulevard
Philadelphia, PA 19104-4318
Office: 215-590-3931
Fax: 215-590-3770
Lab: 215-590-9930
Education:
B.E.S. (Biomedical Engineering)
Johns Hopkins University, Baltimore, MD, 1986.
M.D. (Medicine)
Columbia University College of Physicians and Surgeons, New York, NY, 1990.
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Description of Research Expertise

The Hogarty Lab studies the childhood solid tumor neuroblastoma with the goal of identifying principal oncogenic pathways for the development of novel therapeutics. There are currently three main projects within the lab focused on (1) the contributions of polyamines to neuroblastoma pathogenesis; (2) the role Bcl2 family proteins and mitochondria play in defining stress sensitivity and resistance patterns; and (3) the role chromatin remodeling BAF complexes (Swi/Snf) play in tumor pathogenesis.

Current polyamine-related efforts utilize targeted inhibitors of polyamine metabolism to credential polyamine homeostasis as an essential signaling module downstream of MYC in oncogenesis. We use complementary preclinical models (human xenografts and transgenic mouse models) to define the extent of cancer cell intrinsic (protein stress) and extrinsic (altered tumor immunoenvironment) activities.

Our Bcl2 functional profiling studies have led to the recognition of heterogeneity in major survival dependencies for neuroblastoma that appear hardwired in tumors. We are exploring biomarkers of Bcl2 dependence to triage Bcl2 inhibitors for this subset, and using Mcl1-dependent tumors for functional screening to identify novel Mcl1 antagonists. Importantly, we have identified a mitochondrial phenotype for multidrug resistance using this platform.

Finally, we identified mutations in ARID1A and ARID1B in highest risk lethal neuroblastomas. These BAF complex members are proposed to alter neural differentiation programs through effects on chromatin remodeling and we are characterizing BAF membership and activities to define principal mechanisms.

Selected Publications

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.

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.

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.

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.

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.

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.

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.

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.: Circulating tumor DNA for the detection and monitoring of human malignancies. Science Translational Medicine 6(224): 224, 2014.

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.

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.

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Last updated: 12/16/2014
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