Research Faculty

Mark Kieran, MD, PhD

 

Department Hematology/Oncology
Hospital Title Director, Pediatric Medical
Neuro-Oncology
Academic Title Associate Professor of Pediatrics
Phone 617-632-4907
Fax 617-632-4897
Email Mark Kieran
Location Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215

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 SuperDoctors.com
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

Key Publications

  • Mundel TM, Yliniemi AM, Maeshima Y, Sugimoto H, Kieran M, Kalluri R. Type IV collagen a6 chain-derived non-collagenous domain 1 (a6(IV)NC1) inhibits angiogenesis and tumor growth. Intern J Cancer 2008 April 15;122(8):1738-44. 
     
  • Xie L, Palmsten K, Macdonald B, Kieran MW, Potenta S, Vong S, Kalluri R. Basement membrane derived fibulin-1 and fibulin-5 function as angiogenesis inhibitors and suppress tumor growth. Exp Biol Med 2008 Feb;233(2):155-62.
     
  • MacDonald TJ, Stewart CF, Kocak M, Goldman S, Ellenbogen RG, Phillips P, Lafond D, Poussaint TY, Kieran MW, Boyett JM, Kun LE. Phase I clinical trial of celingitide in children with refractory brain tumors: Pediatric Brain Tumor Consortium Study PBTC-012. J. Clin Oncol 2008 Feb 20;26(6):919-24. 
     
  • Kesari S, Schiff D, Henson JW, Muzikansky A, Gigas DC, Doherty L, Batchelor TT, Longtine JA, Ligon KL, Weaver S, Laforme A, Ramakrishna N, Black PM, Drappatz J, Ciampa A, Folkman J, Kieran M Wen PY. Phase II study of temozolomide, thalidomide, and celecoxib for newly diagnosed glioblastoma in adults. Neuro Oncol. 2008 Jun;10(3):300-8. Epub 2008 Apr 10.
     
  • Gilheeney SW, Saad A, Chi S, Turner C, Ullrich NJ, Goumnerova L, Scott RM, Marcus K, Lehman L, De Girolami U, Kieran MW. Outcome of pediatric pineoblastoma after surgery, radiation and chemotherapy. J Neurooncol. 2008 Aug;89(1):89-95. Epub 2008 Apr 16.
     
  • Sauvageot CM, Weatherbee JL, Kesari S, Winters SE, Barnes J, Dellagatta J, Ramakrishna NR, Stiles CD, Kung AL, Kieran MW, Wen PY. Efficacy of the HSP90 inhibitor 17-AAG in human glioma cell lines and tumorigenic glioma stem cells. Neuro Oncol. 2008 Aug 5. [Epub ahead of print]
     
  • Snuderl M, Chi SN, De Santis SM, Stemmer-Rachamimov AO, Betensky RA, De Girolami U, Kieran MW. Prognostic value of tumor microinvasion and metalloproteinases expression in intracranial pediatric ependymomas. J Neuropathol Exp Neurol. 2008 Sep;67(9):911-20.
     
  • Eikesdal HP, Sugimoto H, Birrane G, Maeshima Y, Cooke VG, Kieran M, Kalluri R. Identification of amino acids essential for the antiangiogenic activity of tumstatin and its use in combination antitumor activity. Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15040-5. Epub 2008 Sep 25.
     
  • Ziegler DS, Kung AL, Kieran MW. Anti-apopotosis mechanism in malignant gliomas. J Clin Onc. 2008 Jan 20;26(3):493-500.
     
  • Chi SN, Zimmerman MA, Yao X, Cohen KJ, Burger P, Biegel JA, Rorke-Adams LB, Fisher MJ, Janss A, Mazewski C, Goldman S, Manley PE, Bowers DC, Bendel A, Rubin J, Turner CD, Marcus KJ, Goumnerova L, Ullrich NJ, Kieran MW. Intensive Multimodality Treatment for Children With Newly Diagnosed CNS Atypical Teratoid Rhabdoid Tumor. J Clin Oncol. 2009 Jan 20;27(3):385-9.
     
  • Kieran MW, Supko JG, Wallace D, Fruscio R, Poussaint TY, Phillips P, Pollack I, Packer R, Boyett JM, Blaney S, Banerjee A, Geyer R, Friedman H, Goldman S, Kun LE, Macdonald T; Pediatric Brain Tumor Consortium. Phase I study of SU5416, a small molecule inhibitor of the vascular endothelial growth factor receptor (VEGFR) in refractory pediatric central nervous system tumors. Pediatr Blood Cancer. 2009 Feb;52(2):169-76.
     
  • Samuel DP, Wen PY, Kieran MW. Antiangiogenic (metronomic) chemotherapy for brain tumors: current and future perspectives. Expert Opin Investig Drugs. 2009 Jul;18(7):973-83.
     
  • Manley P, Li X, Turner C, Chi S, Zimmerman MA, Chordas C, Gordon A, Baker A, Ullrich NJ, Goumnerova L, Marcus K, Hoffman K, Kieran MW. A prospective, blinded analysis of A-PROTEIN (recoverin or CAR protein) levels in pediatric patients with central nervous system tumors. Pediatr Blood Cancer. 2009 Sep;53(3):343-7.
     
  • Turner CD, Chordas CA, Liptak CC, Rey-Casserly C, Delaney BL, Ullrich NJ, Goumnerova LC, Scott RM, Begley HC, Fletcher WJ, Yao X, Chi S, Kieran MW. Medical, psychological, cognitive and educational late-effects in pediatric low-grade glioma survivors treated with surgery only. Pediatr Blood Cancer. 2009 Sep;53(3):417-23.
     
  • Herrington B, Kieran MW. Small molecule inhibitors in children with malignant gliomas. Pediatr Blood Cancer. 2009 Sep;53(3):312-7.
     
  • Ayala F, Dewar R, Kieran M, Kalluri R. Contribution of bone microenvironment to leukemogenesis and leukemia progression. Leukemia. 2009 Dec;23(12):2233-41; Epub 2009 Sept 3.
     
  • MacConaill LE, Campbell CD, Kehoe SM, Bass AJ, Hatton C, Niu L, Davis M, Yao K, Hanna M, Mondal C, Luongo L, Emery CM, Baker AC, Philips J, Goff DJ, Fiorentino M, Rubin MA, Polyak K, Chan J, Wang Y, Fletcher JA, Santagata S, Corso G, Roviello F, Shivdasani R, Kieran MW, Ligon KL, Stiles CD, Hahn WC, Meyerson ML, Garraway LA. Profiling critical cancer gene mutations in clinical tumor samples. PLoS One. 2009 Nov 18;4(11):e7887.
     
  • Zacharoulis S, Chi S, Kadota R, Kieran M. Biological modification strategies following marrow ablative, high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell rescue (AHSCR) for pediatric brain tumors. Pediatr Blood Cancer. 2010 Apr;54(4):654-
     
  • Rauen KA, Schoyer L, McCormick F, Lin AE, Allanson JE, Stevenson DA, Gripp KW, Neri G, Carey JC, Legius E, Tartaglia M, Schubbert S, Roberts AE, Gelb BD, Shannon K, Gutmann DH, McMahon M, Guerra C, Fagin JA, Yu B, Aoki Y, Neel BG, Balmain A, Drake RR, Nolan GP, Zenker M, Bollag G, Sebolt-Leopold J, Gibbs JB, Silva AJ, Patton EE, Viskochil DH, Kieran MW, Korf BR, Hagerman RJ, Packer RJ, Melese T. Proceedings from the 2009 genetic syndromes of the Ras/MAPK pathway: From bedside to bench and back. Am J Med Genet A. 2010 Jan;152A(1):4-24.
     
  • Huttner AJ, Kieran MW, Yao X, Cruz L, Ladner J, Quayle K, Goumnerova LC, Irons MB, Ullrich NJ. Clinicopathologic study of glioblastoma in children with neurofibromatosis type 1. Pediatr Blood Cancer. 2010 Mar 22 [Epub ahead of print].
     
  • Kieran MW, Walker D, Frappaz D, Prados M. Brain Tumors: From Childhood, Through Adolescence and into Adulthood. JCO, April 2010 (in press)
     
  • Panigrahy D, Kaipainen A, Butterfield CE, Chaponis DM, Laforme AM, Folkman J, Kieran MW. Inhibition of tumor angiogenesis by oral etoposide. Experimental and Therapeutic Medicine. 2010; 1: 739-746.
     
  • Lai JS, Zelko F, Butt Z, Cella D, Kieran MW, Krull KR, Magasi S, Goldman S.  Parent-perceived child cognitive function: results from a sample drawn from the US general population.  Childs Nerv Syst. 2010 Jul 23. [Epub ahead of print] PMID: 20652814.
     
  • Geyer JR, Stewart CF, Kocak M, Broniscer A, Phillips P, Douglas JG, Blaney SM, Packer RJ, Gururangan S, Banerjee A, Kieran MW, Kun LE, Gilbertson RJ, Boyett JM.  A phase I and biology study of gefitinib and radiation in children with newly diagnosed brain stem gliomas or supratentorial malignant gliomas.  Eur J Cancer. 2010 Dec;46(18):3287-93. [Epub 2010 Aug 12] PMID: 20708924.
     
  • Ullrich NJ, Zimmerman M, Smith E, Irons M, Marcus K, Kieran MW.  Association of Rapidly Progressive Moyamoya Syndrome With Bevacizumab Treatment for Glioblastoma in a Child With Neurofibromatosis Type 1.  J Child Neurol. 2010 Sep 7. [Epub ahead of print] PMID: 20823033.
     
  • Garcia I, Mayol G, Rodriguez E, Sunol M, Gershon TR, Rios J, Cheung NK, Kieran MW, George RE, Perez-Atayde AR, Casala C, Galvan P, de Torres C, Mora J, Lavarino C.  Expression of the neuron-specific protein CHD5 is an independent marker of outcome in neuroblastoma.  Mol Cancer. 2010 Oct 15;9(1):277. [Epub ahead of print] PMID: 20950435.
     
  • Prabhu SP, Ng S, Vajapeyam S, Kieran MW, Pollack IF, Geyer R, Haas-Kogan D, Boyett JM, Kun L, Poussaint TY. DTI assessment of the brainstem white matter tracts in pediatric BSG before and after therapy. Childs Nerv Syst. 2011 Jan;27(1):11-8 [Epub 2010 Nov 4] PMID: 21052693.
     
  • Winkfield KM, Tsai HK, Yao X, Larson E, Neuberg D, Pomeroy SL, Ullrich NJ, Cohen LE, Kieran MW, Scott RM, Goumnerova LC, Marcus KJ.  Long-term clinical outcomes following treatment of childhood craniopharyngioma.  Pediatr Blood Cancer. 2011 Jul 1;56(7):1120-6. doi: 10.1002/pbc.22884. Epub 2010 Dec 1. PMID: 21488157.
     
  • Chaponis D, Barnes JW, Dellagatta JL, Kesari S, Fast E, Sauvageot S, Panagrahy D,  Greene ER, Ramakrishna N, Wen PY, Kung AL, Stiles C, Kieran MW. Lonafarnib (SCH66336) improves the activity of temozolomide and radiation for orthotopic malignant gliomas. J Neuro-Oncol, 2011 In press. PMID: 21246394.
     
  • Lai J-S, Zelko F, Butt Z, Cella D, Kieran M, Krull K, Magasi S, Goldman S. Perceived cognitive function reported by parents of the United State pediatric population. Child’s Nervous System. 2011 27(2): 285-293 [Epub 2010 Jul 23].  PMID: 20652814.
     
  • Lai JS, Butt Z, Zelko F, Cella D, Krull KR, Kieran MW, Goldman S. Development of a parent-report cognitive function item bank using item response theory and exploration of its clinical utility in computerized adaptive testing.  J Pediatr Psychol. 2011 Aug;36(7):766-79. Epub 2011 Mar 4.
     
  • Gordon CM, Gordon LB, Snyder BD, Nazarian A, Quinn N, Huh S, Giobbie-Hurder A, Neuberg D, Cleveland R, Kleinman M, Miller DT, Kieran MW. Hutchinson-Gilford progeria is a skeletal dysplasia.  J Bone Miner Res. 2011 Jul;26(7):1670-9 doi: 10.1002/jbmr.392. [Epub ahead of print] PMID: 21445982.
     
  • Ziegler DS, Keating J, Kesari S, Fast EM, Zawel L, Ramakrishna N, Barnes J, Kieran MW, Veldhuijzen van Zanten SE, Kung AL.  A small-molecule IAP inhibitor overcomes resistance to cytotoxic therapies in malignant gliomas in vitro and in vivo.  Neuro Oncol. 2011 Jul 1. [Epub ahead of print]  PMID:21724651.
     
  • Pasquier E, Kieran MW, Sterba J, Shaked Y, Baruchel S, Oberlin O, Kivivuori MS, Peyrl P, Diawarra M, Casanova M, Zacharoulis S, Vassal G, Berthold F, Verschuur A, André N.  Moving Forward with Metronomic Chemotherapy: Meeting Report of the 2nd International Workshop on Metronomic and Anti-Angiogenic Chemotherapy in Paediatric Oncology. Translational Oncology 2011 Aug:4(4):189-197.
     
  • Rajagopal MU, Hathout Y, Macdonald TJ, Kieran MW, Gururangan S, Blaney SM, Phillips P, Packer R, Gordish-Dressman H, Rood BR.  Proteomic profiling of cerebrospinal fluid identifies prostaglandin D2 synthase as a putative biomarker for pediatric medulloblastoma: A pediatric brain tumor consortium study.  Proteomics Clin Appl. 2011 Oct;5(9-10):543. PMID:21984079.
     
  • Geoerger B, Kieran MW, Grupp S, Perek D, Clancy J, Krygowski M, Ananthakrishnan R, Boni JP, Berkenblit A, Spunt SL.  Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma.  Eur J Cancer. 2011 Oct 25. [Epub ahead of print] PMID:22033322.
     
  • Tian Y, Rich BE, Vena N, Craig JM, Macconaill LE, Rajaram V, Goldman S, Taha H, Mahmoud M, Ozek M, Sav A, Longtine JA, Lindeman NI, Garraway LA, Ligon AH, Stiles CD, Santagata S, Chan JA, Kieran MW, Ligon KL.  Detection of KIAA1549-BRAF Fusion Transcripts in Formalin-Fixed Paraffin-Embedded Pediatric Low-Grade Gliomas.  J Mol Diagn. 2011 Nov;13(6):669-77. Epub 2011 Aug 30.  PMID:21884820.
     
  • Rehman M, Jenkins KJ, Juraszek AL, Connor JA, Gauvreau K, Muneeb M, Sena LM, Colan SD, Saia T, Kieran MW. A Prospective Phase II Trial of Vinblastine and Methotrexate in Multivessel Intraluminal Pulmonary Vein Stenosis in Infants and Children.  Congenit Heart Dis. 2011 Nov 11. doi: 10.1111/j.1747-0803.2011.00574.x. [Epub ahead of print].
     
  • Gerhard-Herman M, Smoot LB, Wake N, Kieran MW, Kleinman ME, Miller DT, Schwartzman A, Giobbie-Hurder A, Neuberg D, Gordon LB.  Mechanisms of Premature Vascular Aging in Children With Hutchinson-Gilford Progeria Syndrome.  Hypertension. 2011 Nov 14. [Epub ahead of print]