Dr. Bhatia's research interests include reduced intensity allogeneic stem cell transplantation for the treatment of acute and chronic childhood leukemias with special interest in Acute Myeloid Leukemia (AML); as well as the safety and efficacy of stem cell transplantation for the treatment of Hemoglobinopathies and Immunodeficiencies. She is the Clinical Director of the Pediatric Blood & Marrow Transplantation (BMT) program, and the Medical Director of the Quality Management Program for the Division of Pediatric BMT. Dr. Bhatia is also the founder and director of the Monthly Pediatric Immunodeficiency Outpatient Clinic which provides Muli-Disciplinary care in one clinical setting to children with Immunodeficiencies. Specialists that participate include but are not limited to genetics, infectious diseases, dermatology, and neurology.

Dr. Satwani is active in both clinical and translational research. He is currently the Principal Investigator of an open study funded by Osiris Therapeutics: A Phase III, Randomized, Double Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Prochymal™ (Ex-vivo Cultured Adult Human Mesenchymal Stem Cells) Infusion for the Treatment of Patients Who Have Failed to Respond to Steroid Treatment for Acute GVHD.

Dr. Satwani is also Co- Investigator of studies funded by the Pediatric Cancer Research Foundation (PCRF) for work in the PCRF Laboratory at Morgan Stanley Children's Hospital of NY Presbyterian. The focus is on continued research into the molecular and/or proteomic basis of selected pediatric solid tumors and hematological malignancies, to perform basic and translational research in developmental and tumor immunology, conduct laboratory research in transplantation and stem cell biology and to execute translational and clinical research in selected pediatric cancers and lethal blood/immune disorders.

Dr. George joined the Division of Pediatric BMT in 2001 and since that time has had a leading role in enhancing the BMT Outpatient Center by serving as the BMT Outpatient Director. She brings expertise/experience in the areas of unrelated donor transplantation and infectious complications of allo BMT. Dr. George is the BMT Division representative physician for the National Marrow Donor Program and oversees the NMDP sponsored clinical research protocols.

Dr. Hart is an Associate Clinical Professor of Pediatrics with extensive experience in the care of patients with sickle-cell disease, thalassemia and disorders of hemostasis. He has a special interest in the diagnosis and treatment of lead poisoning.

Dr. Weiner has been involved at a national level in the treatment of children and adolescents with Hodgkin's disease. His leadership of a Pediatric Oncology Group protocol more than 20 years ago demonstrated that early response to therapy was key to long-term survival; this approach is now the paradigm upon which all present and future studies are based. In addition, his visionary leadership has been instrumental in establishing programs for alternate medicine, and for the care of adolescents and young adults.

The research program in Dr. Ferrando's leukemia research laboratory focuses on the identification of new molecular therapies for acute leukemias. Using highly innovative tools and genomic approaches the Ferrando lab has identified mutations in key genes responsible for the malignant transformation of leukemic cells. Some of their latest work shows that blocking the activity of these mutations with targeted drugs impairs leukemic cell growth and can reverse chemotherapy resistance.

Dr. Garvin is a national leader in the field of brain tumor clinical investigation. He has been the principal investigator of a Children's Cancer Group study for the treatment of ependymoma and is an active participant in the Pediatric Brain Tumor Consortium. As section leader he coordinates the efforts of the Morgan Stanley Children's Hospital of New York's multi-disciplinary team of neurosurgeons, radiation oncologists, and child neurologists.

Dr. Bender is the Director of the Pediatric Cancer Foundation Developmental Therapeutics Program, which is one of only 21 Phase I research programs supported by the National Cancer Institute (NCI) and the Children's Oncology Group (COG). They are also members of the New Approaches to Neuroblastoma Therapy (NANT) and Therapeutic Advances in Childhood Leukemia (TACL) consortia for which she serves as local Principal Investigator. Additionally, she is the clinical translational member of the Pediatric Tumor Biology laboratory which focuses on the biologic effects of vascular endothelial growth factor (VEGF) blockade and other targeted therapies on experimental models of pediatric solid tumors. She led the first pediatric trial of bevacizumab, an anti-VEGF monoclonal antibody, in children with relapsed solid tumors and is recognized as a clinical leader in the field of pediatric antiangiogenesis. She is also interested in studying patient decision making and quality of life on Phase I trials. She sits on the COG Steering Committees for Developmental Therapeutics and Bioethics, and the COG Bone Sarcoma and Neuroblastoma Disease Committees. Her clinical practice is limited to Solid tumors (e.g. neuroblastoma, sarcoma and germ cell tumors) and phase I consultations.

Dr. Kelly is the director of the Pediatric Leukemia/Lymphoma program, where she also serves as the local principal investigator for several Phase III and other correlative trials for the management of acute lymphoblastic leukemia through the Dana Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium. She is leading an investigation of how dietary intake of micronutrients such as folate and antioxidants impact toxicity to chemotherapy. In the Children's Oncology Group (COG), she is a member of the Hodgkin lymphoma steering committee. She chaired a national trial of the chemotherapy regimen, BEACOPP, in children and adolescents with high risk Hodgkin lymphoma that resulted in the best outcome of any trial in this subgroup of patients. She is currently chairing the successor trial for high risk Hodgkin lymphoma that will build upon these results. She is also leading an effort to incorporate measures of quality of life into treatment trials across risk groups in COG Hodgkin lymphoma trials.

She is also the Medical Director of the Integrative Therapies Program for Children with Cancer, a program which provides free integrative clinical services and educational resources and to children with cancer and their families through and beyond cancer treatment. She is the principal investigator of numerous research trials investigating the use of complementary supportive therapies among children with cancer, including studies on acupuncture and herbs such as milk thistle. She has led several studies examining the effects of antioxidant supplements during chemotherapy for cancer. She is a member of the COG Cancer Control steering committee and she serves as chair of the Integrative Therapies Committee, where she is leading efforts to evaluate different integrative therapies such as fish oils for neurocognitive dysfunction and acupressure for nausea treatment in the management of children with brain tumors. She is a member of the National Cancer Institute's PDQ Complementary and Alternative Medicine Editorial Board. She is also a member of the Board of Directors of the Society of Integrative Oncology (SIO) and she is the Scientific Chair of the 2009 Annual meeting.

Dennis John Kuo M.D. has a part of our team since 2006. His clinical interests are in the treatment, supportive care and long-term survivorship issues surrounding the care of patients with leukemias and lymphomas. He speaks Mandarin Chinese and Spanish, and sees patients at both the Herbert Irving Child & Adolescent Oncology Center at Columbia University Medical Center and our affiliate, St. Joseph's Children's Hospital in Paterson, New Jersey.

Unrestrained proliferation and differentiation block are hallmarks of childhood cancers of the nervous system. Our laboratory is using an interdisciplinary approach that includes cellular biology, mouse genetics and biochemical methods to integrate basic research with an understanding of malignant transformation caused by two transcription factors that are critically involved in normal development of the nervous system, namely Id2 and N-Myc.

- The Id2 protein is a general inhibitor of differentiation and positive regulator of proliferation that is frequently recruited by oncogenic signals to mediate multiple hallmarks of neoplasia. Our work aims at identifying the molecular pathways engaged by Id2 to prevent differentiation, promote cell proliferation and induced invasion and neoangiogenesis in cancer of the nervous system.

- To address the function of deregulated N-Myc in neuroblastoma we identified the natural protein complexes engaged by N-Myc using a state-of-the-art proteomic approach in human neuroblastoma cells. Among the N-Myc protein partners we identified the ubiquitin ligase Huwe1. Huwe1 targets N-Myc protein for degradation during differentiation and cell cycle arrest in the developing nervous system and neuroblastoma cells. The major implication of this work is that continuous self-renewal and inhibition of differentiation of neural stem cells requires protection of the N-Myc oncoprotein from the destructive activity of the Huwe1. The most exciting novel finding that originated from the identification of the Huwe1-N-Myc pathway in neural cells is that primary neural tumors in humans carry focal genetic deletions of the Huwe1 gene. These results identify Huwe1 as a new tumor suppressor gene in neural tumors and establish an unprecedented link between neural stem cell renewal and tumor development.

Dr. Levine's clinical interests are in the treatment of pediatric leukemia and lymphoma. As the medical director of the Center for Survivor Wellness, she is interested in understanding and evaluating the medical and psychosocial long term complications of treatment for pediatric cancer. The research interests of the Center include fertility preservation, maximizing optimal nutrition and exercise in survivors, and understanding barriers to long term care.

Dr. Stephen Sands is actively involved in investigating the neuropsychological and quality of life late effects arising from the treatment of pediatric oncology. Specific international and national protocols that Dr. Sands has assumed a leadership role in involve the examination of the long-term impacts from the use of cranial irradiation and chemotherapy for the treatment of various brain tumors and acute lymphoblastic leukemia upon the developing brain, as well as the social-emotional and behavioral sequelae.

The main focus of Dr. Sulis's research in the laboratory is the study of the role of NOTCH1 in the development of T cell ALL. Until now almost 2/3 of the cases of T-ALL have been found to have aberrant expression of the NOTCH1 pathway by either activating mutations of the NOTCH1 receptor or inactivating mutations of FBW7 which normally degrades NOTCH1. They believe that activated NOTCH1 pathway may be a universal event in T-ALL, therefore she is interested in finding alternative, yet unknown ways, to activate it. Currently she is studying the expression profile of mouse T-cell lymphoblastic lymphomas originated from different transgenic models. She has found that a subset of them carry activated Notch1 in the absence of any of the mutations mentioned above suggesting the existence of alternative mechanisms of Notch1 activation. By comparing the expression profile of the Notch 1 wild type tumors with the Notch1 mutated ones and the ones which are neither wild type nor mutated but have an aberrantly activated pathway, they hope to identify genes or pathways that can interfere with and activate Notch1 and ultimately lead to the development of T-cell lymphomas. The candidate genes or pathways will then be validated with a series of experiments in the second part of the project.

The laboratory of Dr. Darrell Yamashiro, Pediatric Oncology, examines the role of angiogenesis in the growth and metastasis of pediatric solid tumors. They have demonstrated that blocking the angiogenic factor vascular endothelial growth factor (VEGF) inhibited growth of xenografts tumors such as neuroblastoma, Wilms, and hepatoblastoma. These preclinical studies led to the Children's Oncology Group/NCI Phase I study of the anti-VEGF antibody bevacizumab (Avastin) in children, chaired by Dr. Julia Glade Bender, Pediatric Oncology, and Dr. Yamashiro (J. Clin. Oncology, 26: 399-405, 2008). His laboratory is currently examining the role of alternative angiogenic pathways and the mechanisms by which tumors evade anti-angiogenic therapy. These include the Notch and placental growth factor/VEGFR1 pathways.