Research Overview

Research, particularly as it relates to translational medicine, has become progressively more dependent on strong collaborations. In this regard, my research efforts have been directed towards projects with translational potential and team building. My current laboratory space is located within the Vascular Biology Program, Department of Surgery at Boston Children’s Hospital and is comprised of basic and clinical faculty from a number of different departments. Originally under the Chairmanship of Dr Judah Folkman and now Dr Marsha Moses, my independent laboratory efforts are focused on identifying novel biologic and anti-angiogenic agents that can be translated into the clinic. My lab's initial studies examined the role of traditional chemotherapy such as cyclophosphamide and etoposide provided in low doses to target angiogenesis (called metronomic chemotherapy). A number of preclinical studies resulted from this work with direct translation into pediatric clinical trials for agents such as oral etoposide, oral cyclophosphamide, celecoxib, thalidomide and PPARa agonists. In order to better understand the underlying mechanisms for the activity observed, Dr Dipak Panigrahy and I have been examining the role of the EETs lipid signaling pathway. A second and related approach has been the pre-clinical evaluation of novel antiangiogenic agents that are moving towards clinical trials. To promote rapid translation to pediatric patients, particularly for use in central nervous system tumors, my laboratory, in conjunction with our pre-clinical models group (Dr Andrew Kung), adult neuro-oncology (Dr Patrick Wen) and Cancer Biology (Dr Chuck Stiles), we have developed orthotopic model system that provides rapid evaluation of novel agents. These have led to a number of pediatric clinical trials including SCH66336, 17-AAG, SU5416 and AZD2171. Finally, my laboratory has embraced the importance of molecular profiling of tumors as an important facet of designing improved therapy. Initially focused on pediatric low-grade gliomas, in conjunction with the Center for Cancer Genome Discovery at DFCI and the Broad Institute, we have molecularly profiled almost 500 primary tumor samples from children with low-grade gliomas and performed detailed mutation analysis in half of these. Important discoveries have resulted from these efforts that are being translated into the clinic and similar approaches have recently been completed for ATRT and DIPG.

Clinical Overview

As Director, Pediatric Medical Neuro-Oncology, my groups’ focus remains on supporting our multi-disciplinary program with expertise in all aspects of clinical care including 1) Protocol driven treatment evaluation through a multidisciplinary pediatric brain tumor clinic, 2) Development of a comprehensive pediatric brain tumor survivorship program, 3) Development of a translational research base with an emphasis on taking laboratory findings into the clinic, and 4) A disease specific sub-fellowship training program for individuals interested in Pediatric Neuro-Oncology. Through the Children’s Oncology Group (COG), I am on the Steering Committee of the Neuro-Oncology Disease Center and Chair the malignant glioma section (shared with Dr. Ken Cohen). I have Chaired the DOD funded NF1 Consortium brain tumor committee and I am the Harvard PI of the Pediatric Oncology Experimental Therapeutics Investigators Consortium (POETIC). With increasing importance of small groups of dedicated institutions to complete specific studies, almost one third of our protocols are not directly affiliated with any one Cooperative Group. Rather, collaborations locally, nationally and internationally have become an import part of achieving our study priorities, while supporting other groups with similar needs. Due to the increasing importance of biologic-based profiling of tumors to guide interventions, we created the first comprehensive DFCI/CH tissue bank. This has now expanded to other Harvard institutions. Finally, I have a long-standing interest in supporting program development in developing countries and travel regularly to China, India, Turkey, and Egypt for these on-going program efforts.

About Mark Kieran

Mark Kieran received his PhD from the University of Alberta, Edmonton, Canada, and his MD from the University of Calgary. He completed postgraduate training in molecular biology at the Pasteur Institute in Paris. He completed a pediatric residency at McGill University in Montreal and a postdoctoral fellowship at Children's Hospital Boston.

Awards (from 2002):

  • 2002: Nick Palmer Lecture Award, ISPNO, London, England
  • 2005: 2nd International Germ Cell Meeting, Los Angeles
  • 2006: Triple Winner Award, Boston, MA
  • 2006: Voted An America’s Top Cancer Doctor
  • 2006: Letter of Appreciation, Seoul National University, Seoul, Korea
  • 2007: Voted An America’s Top Cancer Doctor
  • 2008: Voted An America’s Top Cancer Doctor
  • 2009: Top Doctors in Boston, Boston Magazine
  • 2009: Voted An America’s Top Cancer Doctor
  • 2009: Appreciation Award, Children’s Cancer Hospital Egypt
  • 2010: Top Doctors in Boston, Boston Magazine
  • 2010: Excellence Award, Egyptian Society of Neurosurgeons, Sharm El Sheikh
  • 2010: Certificate of Appreciation in Teaching, University of Constantine, Algeria
  • 2010: National Brain Tumor Society Billy Grey Research Chairman Award. San Francisco
  • 2010: Voted An America’s Top Cancer Doctor
  • 2011: Mill Foundation for Kid’s Above and Beyond Award, Southington CT
  • 2011: Selected Top Doctors in Boston, Doximity
  • 2011: America's Top Doctors for Cancer, Castle Connolly
  • 2011 – 2012: Marquis Who's Who in Medicine and Healthcare
  • 2011: Top Doctors in Boston, Boston Magazine
  • 2012: Nominated, Schwartz Compassionate Care Giver Award

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Researcher Areas

  • Anti-Angiogenesis and Novel Molecularly Targeted Therapy in Neuro-Oncology

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