Associate professor of Pediatrics, University of Pennsylvania School of Medicine
AddressDivision of Oncology The Children's Hospital of Philadelphia Colket Translational Research Building, Room 3020 3501 Civic Center Boulevard
The Hogarty lab works on defining the cancer biopathways that support neuroblastoma tumourigenesis with particular focus on understanding how neuroblasts with MYCN amplification avoid engaging the latent apoptosis programs usually activated with dergulated oncogene activity. We study experimental therapeutics targeting key neuroblast survival pathways.
- 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., Columbia University College of Physicians and Surgeons, New York, NY (1990)
- B.E.S., Biomedical Engineering, Johns Hopkins University, Baltimore, MD (1986)
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.
- Suganuma Rie, Wang Larry L, Sano Hideki, Naranjo Arlene, London Wendy B, Seeger Robert C, Hogarty Michael D, Gastier-Foster Julie M, Look A Thomas, Park Julie R, Maris John M, Cohn Susan L, Amann Gabriele, Beiske Klaus, Cullinane Catherine J, d'Amore Emanuele S G, Gambini Claudio, Jarzembowski Jason A, Joshi Vijay V, Navarro Samuel, Peuchmaur Michel, Shimada Hiroyuki. Peripheral neuroblastic tumors with genotype-phenotype discordance: A report from the Children's Oncology Group and the International Neuroblastoma Pathology Committee.. Pediatric blood & cancer. Vol 60(3) . 2013 Mar:363-70.
- Boiani Mariana, Daniel Cristina, Liu Xueyuan, Hogarty Michael D, Marnett Lawrence J. The stress protein BAG3 stabilizes Mcl-1 and promotes survival of cancer cells and resistance to ABT-737.. The Journal of biological chemistry. 2013 Jan.
- 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.
- 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.
- 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.
- Hogarty Michael D, Maris John M. PI3King on MYCN to improve neuroblastoma therapeutics.. Cancer cell. Vol 21(2) . 2012 Feb:145-7.
- 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.
- Dubois Steven G, Geier Ethan, Batra Vandana, Yee Sook Wah, Neuhaus John, Segal Mark, Martinez Daniel, Pawel Bruce, Yanik Greg, Naranjo Arlene, London Wendy B, Kreissman Susan, Baker David, Attiyeh Edward, Hogarty Michael D, Maris John M, Giacomini Kathleen, Matthay Katherine K. Evaluation of Norepinephrine Transporter Expression and Metaiodobenzylguanidine Avidity in Neuroblastoma: A Report from the Children's Oncology Group.. International journal of molecular imaging. Vol 2012. 2012:250834.
- De Preter Katleen, Mestdagh Pieter, Vermeulen Joëlle, Zeka Fjoralba, Naranjo Arlene, Bray Isabella, Castel Victoria, Chen Caifu, Drozynska Elzbieta, Eggert Angelika, Hogarty Michael D, Izycka-Swieszewska Ewa, London Wendy B, Noguera Rosa, Piqueras Marta, Bryan Kenneth, Schowe Benjamin, van Sluis Peter, Molenaar Jan J, Schramm Alexander, Schulte Johannes H, Stallings Raymond L, Versteeg Rogier, Laureys Geneviève, Van Roy Nadine, Speleman Frank, Vandesompele Jo. miRNA expression profiling enables risk stratification in archived and fresh neuroblastoma tumor samples.. Clinical cancer research : an official journal of the American Association for Cancer Research. Vol 17(24) . 2011 Dec:7684-92.
- Liu Grant T, Mahoney Nicholas R, Avery Robert A, Menacker Sheryl J, Wilson Martin C, Hogarty Michael D, Maris John M. Pediatric horner syndrome.. Archives of ophthalmology. Vol 129(8) . 2011 Aug:1108-9; author reply 1109.