Michael D. Hogarty, MD

Michael D. Hogarty, MD
Michael D. Hogarty, MD, is an Attending Physician in the Division of Oncology at Children's Hospital of Philadelphia. He has a special interest in neuroblastoma and histiocyte disorders.

Areas of Expertise: Histiocytic diseases (LCH and JXG), Germ cell tumors (teratomas and malignant germ cell tumors), Neuroblastoma translational research, Physician-Scientist education
Locations: Main Campus

Background

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 breadth 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

Medical School

MD - Columbia University College of Physicians and Surgeons, New York, NY

Internship

Pediatrics - Children’s Memorial Hospital/Northwestern University, Chicago, IL

Residency

Pediatrics - Children's Memorial Hospital/Northwestern University, Chicago, IL (Chief Resident)

Fellowship

Pediatric Hematology/Oncology - The Children's Hospital of Philadelphia, Philadelphia, PA

Board Certification

Hematology-Oncology
Pediatrics

Titles and Academic Titles

Attending Physician

Associate Director, Pediatric Hematology/Oncology Fellowship

Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania

Conditions Treated

Departments and Services

Research Interests

Publications

Papers

2015

Eleveld TF, Oldridge DA, Bernard V, Koster J, Daage LC, Diskin SJ, Schild L, Bentahar NB, Bellini A, Chicard M, Lapouble E, Combaret V, Legoix-Né P, Michon J, Pugh TJ, Hart LS, Rader J, Attiyeh EF, Wei JS, Zhang S, Naranjo A, Gastier-Foster JM, Hogarty MD, Asgharzadeh S, Smith MA, Guidry Auvil JM, Watkins TB, Zwijnenburg DA, Ebus ME, van Sluis P, Hakkert A, van Wezel E, van der Schoot CE, Westerhout EM, Schulte JH, Tytgat GA, Dolman ME, Janoueix-Lerosey I, Gerhard DS, Caron HN, Delattre O, Khan J, Versteeg R, Schleiermacher G, Molenaar JJ, Maris JM. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations. Nat Genet. 2015 Aug;47(8):864-71.

Bassiri H, Benavides A, Haber M, Gilmour SK, Norris MD, Hogarty MD. Translational development of DFMO for the treatment of neuroblastoma. Transl Pediatr. 2015 Jul;4(3):226-38.

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 2014. 26(5): 682-694 [PMID: 25517749].

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 2014. Feb 20; 5: e1072 [PMID: 24556687; PMCID: 3944256].

Abstracts

2015

Temple W, Mendelsohn L, Kim G, Nekritz E, Gustafson WC, Lin L, Giacomini K, Naranjo A, Van Rhyn C, Yanik GA, Kreissman SG, Hogarty MD, Matthay KK, DuBois SG. Vesicular monoamine transporter protein expression in neuroblastoma: a report from the Children’s Oncology Group. American Association for Cancer Research Annual Meeting; April 18-22, 2015; Philadelphia, PA.

Wang L, Teshiba R, Ikegaki N, Tang XX, Naranjo A, London WB, Hogarty MD, Gastier-Foster J, Look AT, Park JR, Maris JM, Cohn SL, Seeger RC, Asgharzadeh S, Shimada H. Immunohistochemical detection of MYCN protein and MYC protein identifies highly aggressive neuroblastomas. American Association for Cancer Research Special Conference- MYC: from biology to therapy; January 7-10, 2015; La Jolla, CA.

2014

Wang L, Teshiba R, Naranjo A, Ikegaki N, Tang XX, Gastier-Foster J, Asgharzadeh S, Seeger RC, Hogarty MD, London WB, Cohn SL, Park JR, Maris JM, Shimada H. MYC/MYCN protein expression in neuroblastoma, undifferentiated and poorly differentiated subtype- cMYC activation is a new marker for aggressive tumor behavior: a report from the COG Neuroblastoma Committee. Advances in Neuroblastoma Research, May 13-16, 2014; Cologne, Germany.

Ambros I, Brunner C, Bogen D, Amann G, Abbasi R, Gurtl-Lackner B, Hogarty MD, Martinsson T, Ladenstein R, Ambros P. Genomic background of neuroblastomas with intra-tumor heterogeneity of MYCN amplification. Advances in Neuroblastoma Research, May 13-16, 2014; Cologne, Germany.

Haber M, Gamble L, Murray J, Ashton L, Purgato S, Milazzo G, Valli E, Perini G, Oberthur A, London WB, Hogarty MD, Fischer M, Marshall M, Ziegler D, Norris M. The entire polyamine gene pathway is coordinately regulated by the MYCN oncogene to sustain polyamine levels and support neuroblastoma progression. Advances in Neuroblastoma Research, May 13-16, 2014; Cologne, Germany.

Woodburn T, Davidson H, Hogarty MD, Mosse YP, Reynolds CP. The Children’s Oncology Group Cell Culture and Xenograft Repository neuroblastoma cell lines and patient-derived xenografts. Advances in Neuroblastoma Research, May 13-16, 2014; Cologne, Germany.

Goldsmith KC, Laetsch TW, Liu X, Dunbar P, Corrigan KA, Chen M, Reynolds CP, Hogarty MD. Profound therapy resistance in neuroblastoma is characterized by a mitochondrial phenotype. Advances in Neuroblastoma Research, May 13-16, 2014; Cologne, Germany.

Diskin S, McDaniel L, Oldridge DA, Attiyeh E, Asgharzadeh S, Weisenberger DJ, Shen H, Diamond M, Guidry-Auvil J, Davidsen T, Smith M, Gerhard DS, Hogarty MD, London WB, Khan J, Seeger RC, Laird PW, Maris JM. Integrative genomic and epigenomic characterization of stage 4S neuroblastoma. Advances in Neuroblastoma Research, May 13-16, 2014; Cologne, Germany.

Liu X, Tsai PF, Vu A, Sliozberg M, Kim S, Fan HY, Hogarty MD. The ARID1-containing Swi/Snf BAF complex is a driver of poor outcome neuroblastoma. Advances in Neuroblastoma Research, May 13-16, 2014; Cologne, Germany.

Norris M, Di Giacomo S, Purgato S, Valli E, Rihani A,Van Maerken T, Vandesompele J, Speleman F, Versteeg R, Eggert A, Noguera R, Stallings R, Tonini GP, Henderson M, Gamble L, Murray J, Russell A, Ashton L, London WB, Marshall G, Ziegler D, Hogarty MD, Fong K, Bowman RV, Yang IA, Perini G, Haber M. The Ornithine Decarboxylase G317A Polymorphism is Prognostic of Outcome in Primary Neuroblastoma and Differentially Affects Promoter Binding by the MYCN Oncogene. Advances in Neuroblastoma Research, May 13-16, 2014; Cologne, Germany.

Oldridge D, McDaniel L, Attiyeh E, Asgharzadeh S, Diamond M, Guidry-Auvil J, Davidsen T, Smith M, Gerhard DS, Gastier-Foster J, Hogarty MD, London WB, Khan J, Seeger RC, Diskin SJ, Maris JM. High-risk neuroblastoma genomic plasticity allows for significant clonal evolution under selective pressure of chemotherapy. Advances in Neuroblastoma Research, May 13-16, 2014; Cologne, Germany.

Asgharzadeh S, Shen H, Gnanchandran J, Ji L, Hung L, Wakamatsu P, Weisenberger DJ, Fischer M, Attiyeh E, Wei JD, Guidry-Auvil J, Smith M, Gerhard DS, Gastier-Foster J, Hogarty MD, London WB, Oberthur A, Berthold F, Triche T, Shimada H, Sposto R, Khan J, Maris JM, Laird P, Seeger RC. Integrated genomic analyses identifies neural, metabolic and inflammatory subgroups of high-risk neuroblastoma with clinical significance. Advances in Neuroblastoma Research, May 13-16, 2014; Cologne, Germany.

Books

Chapters

2015

Brodeur GM, Hogarty MD, Bagatell R, Mosse YP, Maris JM. Neuroblastoma. In Principles and Practice of Pediatric Oncology, 7th Edition. PA Pizzo and DG Poplack, Eds. Lippincott Williams & Wilkins, Inc.; 2015 (in press).

2011

Hogarty MD, Brodeur GM. Neuroblastoma. In: Arceci R, editor. Rudolph's pediatrics. 22nd ed. New York: McGraw-Hill Professional; 2011.

2010

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.

2009

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.

2002

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.

2000

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.

1998

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.

1996

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.

Posters and Presentations

Invited Lectures

2015

“From the office to the ICU: the basics of histiocytic disorders”-Children’s Hospital of Philadelphia CME Lecture Series; Cherry Hill, NJ, June 2015.

“Neuroblastoma biology: new findings and future treatment options”-Updates in Neuroblastoma Symposium; American Society for Pediatric Hematology/Oncology Annual Meeting 2015; Phoenix, AZ, May 2015.

“Revising the COG neuroblastoma staging and risk classification systems”- Neuroblastoma Biology session, COG National meeting; Atlanta, GA, April 2015.

“Depriving tumors of polyamines as a therapeutic strategy for neuroblastoma”- Jefferson Physician Scientist Association (JPSA), Sydney Kimmel Medical College at Thomas Jefferson University; Philadelphia, PA, April 2015.

“A model of therapy resistance for pediatric cancers”- TTUHSC Cancer Center Grand Rounds, Texas Tech University of the Health Sciences; Lubbock, TX, February 2015.

2014

“Cancer therapy resistance: a mitochondrial-ER phenotype”- MitoCircle Research Seminar; Thomas Jefferson University; Philadelphia, PA, July 2014.

“Developing polyamine pathway antagonists for neuroblastoma therapy”- Translational Oncology Seminar; Nationwide Children’s Hospital; Columbus, OH, May 2014.

“Targeting the polyamine pathway in neuroblastoma-rationale and clinical translation”- Pediatric Oncology Seminar Series; Cincinnati Children’s Hospital Medical Center; Cincinnati, OH, March 2014.

“Pediatric Cancer Therapy Response and Resistance”- Alex’s Lemonade Stand Foundation (ALSF) Corporate Sponsor Summit; Philadelphia, PA, March 2014.

“NANT 2012-01: Phase 1 study of DFMO and celecoxib with cyclophosphamide/topotecan for patients with relapsed or refractory neuroblastoma”- New Approaches to Neuroblastoma Therapy (NANT) Annual Meeting; Redondo Beach, CA, March 2014.

Awards and Honors

2014, Basic Science Poster Award at Advances in Neuroblastoma Research

2009, “Best Producer Academy Award”; given by Oncology Division for best nursing-medical partnership in medical care delivery

2005, University Research Foundation Award (University of Pennsylvania)

2004, Honorary Board Member; The Thomas Peterpaul Foundation

2003, Italian Neuroblastoma Association Award at Advances in Neuroblastoma Research 2004

2001-2003; 2004-05; 2007-08 - Faculty Honor Roll Teaching Award, Children’s Hospital of Philadelphia

2002, Howard Hughes Medical Institute/Burroughs Wellcome Fund Scientific Management Program

2002, Audrey Evans Prize at Advances in Neuroblastoma Research 2002

2000, Burroughs Wellcome Fund Career Award in the Biomedical Sciences

1999, Career Development Award; American Society of Clinical Oncology

1998, Molecular Approach to Pediatric Science-CHRC Award

1998, Young Investigator Award; Advances in Neuroblastoma Research 1998

1997, Molecular Biologics in Clinical Cancer Research Award (K12)

1996, Young Investigator Award; American Society of Clinical Oncology

1995, NIH National Research Service Award (T32)

1995, Fellow Teacher of the Year Award; Children’s Hospital of Philadelphia

1993, Northwestern University Feinberg School of Medicine Resident Teaching Award

1991, PL1 Outstanding Teacher Award; Children’s Memorial Hospital

1985, Alpha Epsilon Delta

Editorial and Academic Positions

Editorial positions

Ad hoc reviewer

Archives of Pediatric and Adolescent Medicine
Biochimica et Biophysica Acta -- Gene Structure and Function
BMC Cancer
Cancer Epidemiology, Biomarkers & Prevention
Cancer Cell
Clinical Cancer Research
Genes Chromosomes & Cancer
Human Genetics
Journal of Cellular Biochemistry
Journal of Clinical Investigation
Journal of Clinical Oncology
Laboratory Investigation
Medical and Pediatric Oncology
Oncogene
Pediatric Blood and Cancer
Pediatric and Developmental Pathology
Pediatric Emergency Medicine
The American Journal of Pathology
The FASEB Journal

Academic and Institutional Committees

2014-present, CCCR Strategic Planning Task Force; Co-Leader-Education Goal, executive committee
2014-present, Director of Research on Pediatric Education, search committee
2014-present, Data Safety Monitoring Committee (DSMC); NO-021 Proton Therapy Protocol, Hospital of the University of Pennsylvania (HUP)
2014-present, Education Committee, Department of Pediatrics
2013-present, Research Institute Scientific Symposium Planning Committee
2012-present, CCCR-ALSF Awards Steering Committee, Division of Oncology
2012-present, Oncology Division Instructor Oversight Committee, co-chair
2012-present, CCCR Biobank Scientific Review Committee
2011-present, Director, Physician-Scientist Recruitment, Pediatrics Residency Program
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

Leadership and Memberships

Memberships in Professional Organizations

2011-present, Society for Pediatric Research

2008-present, Advances in Neuroblastoma Research Association

 - 2012-present, Steering Committee

 - 2008-present, North American-South American Advisory Board

 - 2000-present, Children’s Oncology Group

 - 2011-2013, Biobanking Task Force

 - 2007-present, Neuroblastoma Executive Committee

 - 2006-present, High-Risk Neuroblastoma Task Force

 - 2006-present, Neuroblastoma Biology Committee, chair

 - 2006-present, Neuroblastoma Steering Committee

 - 2001-present, Neuroblastoma Biology Committee

 - 2000-present, Neuroblastoma Strategy Group

2000-present, International Histiocyte Society

1999-present, American Board of Pediatrics, Diplomate

1998-present, American Academy for the Advancement of Science

1998-present, American Society of Pediatric Hematology/Oncology

1996-present, American Association for Cancer Research

1995-present, American Society of Clinical Oncology