Dr. Hogarty has clinical expertise managing patients with neuroblastoma, germ cell tumors (malignant and benign), and histiocytic diseases of childhood (LCH and HLH). 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.
The Hogarty Lab studies the childhood solid tumor neuroblastoma with the goal of identifying principal oncogenic pathways for the development of novel therapeutics.
Keywords: pediatric cancer, neuroblastoma, MYC, Bcl2 signaling, cancer therapy resistance, polyamines
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.
- Associate Professor of Pediatrics at the Children's Hospital of Philadelphia (2009– present)
- Assistant Professor of Pediatrics at University of Pennsylvania School of Medicine (2000 – 2006)
- Assistant Professor of Pediatrics at the Children's Hospital of Philadelphia (2006 – 2009)
- M.D., Medicine, Columbia University College of Physicians and Surgeons, New York, NY (1990)
- B.E.S., Biomedical Engineering, Johns Hopkins University, Baltimore, MD (1986)
- 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. Vol 45(1) . 2012 Jan:12-7.
- Pugh Trevor J, Morozova Olena, Attiyeh Edward F, Asgharzadeh Shahab, Wei Jun S, Auclair Daniel, Carter Scott L, Cibulskis Kristian, Hanna Megan, Kiezun Adam, Kim Jaegil, Lawrence Michael S, Lichenstein Lee, McKenna Aaron, Pedamallu Chandra Sekhar, Ramos Alex H, Shefler Erica, Sivachenko Andrey, Sougnez Carrie, Stewart Chip, Ally Adrian, Birol Inanc, Chiu Readman, Corbett Richard D, Hirst Martin, Jackman Shaun D, Kamoh Baljit, Khodabakshi Alireza Hadj, Krzywinski Martin, Lo Allan, Moore Richard A, Mungall Karen L, Qian Jenny, Tam Angela, Thiessen Nina, Zhao Yongjun, Cole Kristina A, Diamond Maura, Diskin Sharon J, Mosse Yael P, Wood Andrew C, Ji Lingyun, Sposto Richard, Badgett Thomas, London Wendy B, Moyer Yvonne, Gastier-Foster Julie M, Smith Malcolm A, Auvil Jaime M Guidry, Gerhard Daniela S, Hogarty Michael D, Jones Steven J M, Lander Eric S, Gabriel Stacey B, Getz Gad, Seeger Robert C, Khan Javed, Marra Marco A, Meyerson Matthew, Maris John M. The genetic landscape of high-risk neuroblastoma.. Nature genetics. 2013 Jan.
- 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. Vol 72(10) . 2012 May:2565-77.
- 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. Vol 17(5) . 2010 May:872-82.
- Lestini Brian J, Goldsmith Kelly C, Fluchel Mark N, Liu Xueyuan, Chen Niel L, Goyal Bella, Pawel Bruce R, Hogarty Michael D. Mcl1 downregulation sensitizes neuroblastoma to cytotoxic chemotherapy and small molecule Bcl2-family antagonists.. Cancer biology & therapy. Vol 8(16) . 2009 Aug:1587-95.
- 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. Vol 22(5) . 2012 Nov:631-44.