Research: We believe that both clinical and laboratory research are essential to providing the best care for our patients, current and future.

Clinical Research

Clinical Trials

Our membership in cooperative groups and studies include:
· Children's Oncology Group
· National Marrow Donor Program
· Pediatric Blood and Marrow Transplant Consortium (Clinical Trials Network)
· Cord Blood Transplantation Study
· International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry
· Pediatric Aplastic Anemia Cooperative Trials
· New York Regional Thalassemia Network
· Histiocyte Society

Our clinician investigators have leadership positions in many of these groups. Our clinical research is conducted through a number of active collaborations with national cooperative groups. These clinical studies encompass cancer, stem cell (bone marrow) transplantation, acquired aplastic anemia, inherited bone marrow failure syndromes, sickle cell anemia, thalassemia, histiocytic disorders, Gaucher disease and bleeding disorders. We also participate in a number of important pharmaceutical sponsored clinical studies. In particular the Children's Oncology Group (COG) is an organization dedicated to clinical research in the field of pediatric cancer. The Children's Oncology Group is a cooperative cancer treatment group funded by the National Cancer Institute with a network of over 235 institutions that treat children with cancer in North America, Europe, and Australia. The institutions collaborate in clinical research studies aimed at improving treatment for cancer and developing new strategies for the early detection and prevention of cancer. In this manner, the best treatment can be established. It is common medical practice to treat children with cancer on national research studies, which offer the best treatment available for childhood cancer.

Epidemiology
Diamond Blackfan Anemia Registry of North America (DBAR)
Adrianna Vlachos, M.D.
Eva Atsidaftos, B.A., M.A.
Jeffrey M. Lipton, M.D., Ph.D.

Diamond Blackfan anemia (DBA), is an extremely rare, severe anemia of childhood. There are only 1,000 cases of DBA diagnosed worldwide. As such, there are gaps in the understanding of the natural history of this disorder. For this reason, the Diamond Blackfan Anemia Registry of North America was established in 1993 to collect accurate clinical and demographic data on DBA patients and their families. Headquartered in Schneider Children's Hospital, the DBAR is a Natural Heart Lung a Blood Institute funded (RO 1) research tool dedicated to acquiring, analyzing and disseminating information on Diamond Blackfan anemia to affected individuals, their families and medical professionals. The DBAR has collected information on over 420 patients in its database.

The database serves as the substrate for the investigation of the biology and epidemiology of DBA. Indeed the biology and epidemiology of DBA are only partially understood. The database has been developed through a comprehensive questionnaire with follow-up in-person evaluations and telephone interviews and a thorough review of medical records. The patients who need to be evaluated in-person at the General Clinical Research Center of the North Shore-LIJ Research Institute. The project has already provided insight into the epidemiology of this disorder. A second DBA gene has been inferred by linkage analysis using multiplex families from the DBAR. Studies of the epidemiology and genetics of cancer and congenital anomalies are ongoing.

Laboratory Research
Our laboratory research is directed to understanding the cellular and molecular biology of Diamond Blackfan Anemia (DBA) and Fanconi anemia (FA)

Diamond Blackfan anemia and Fanconi anemia
Johnson Liu, M.D.
Steven Arkin, M.D.
Jeffrey M. Lipton, M.D., Ph.D.

Pathogenesis of DBA is still unclear although an intrinsic defect in the erythroid progenitor or even multipotent stem cells resulting in premature or accelerated apoptosis appears to be responsible for the development of anemia. We are currently studying the molecular biological profile of human erythropoiesis as tools to understand the pathogenesis of DBA. We are determining the gene expression during erythropoiesis in normal individuals and erythroid cell lines and how they differ in patients with DBA using state-of-the-art gene microarray technology. Our focus is on understanding the role of RPS-19, a ribosomal protein, found to be mutated in 25% of the patients, in the development of the DBA phenotype. This line of investigation involves the study of cell survival and apoptotic pathways in erythroid cells, characterization of genes that are involved in intracellular signal transduction, and discovery of other DBA genes. Daniella Maria Arturi Foundation and Diamond Blackfan Anemia Foundation fund our studies.

Investigations in the Michael Neisloss Hematopoiesis Research Laboratory are directed at understanding cellular and molecular pathways leading to markedly increased rates of bone marrow aplasia and malignancy in hereditary Bone Marrow Failure disorders. These disorders include Diamond-Blackfan Anemia (DBA), Fanconi Anemia (FA) and Shwachman Diamond Syndrome (SDS). Cellular abnormalities described in these diseases include increased apoptosis (programmed cell death), with or without associated abnormalities in DNA repair and altered cell cycle progression. The resulting, accelerated, transition of these disorders towards aplastic anemia and cancer makes their study highly significant in understanding mechanisms leading to aplastic anemia and leukemogenesis. We hypothesize that abnormal apoptosis observed in these disorders results in depletion of necessary hematopoietic progenitor cells and impose, at the cellular level, a selective pressure to escape vital regulatory mechanisms mediated through apoptotic pathways. These same apoptotic defects render host cells extraordinarily sensitive to cytotoxic effects of cancer chemotherapy, effectively precluding effective treatment of cancer in affected patients.

Studies presently underway in the laboratory include; a) identification of disrupted RPS 19 mediated pathways in Diamond Blackfan Anemia (DBA) and identification of additional genetic loci conveying the DBA phenotype. B) Validation of diagnostic modalities for detection of Fanconi Anemia and correlation of DNA damage with induction of apoptosis and escape from cell cycle homeostatic mechanisms. C) In Vitro evaluation of antibody directed chemotherapy with the objective of reducing the generally fatal toxicity experienced by these patients when receiving chemotherapy treatment for cancer. This in vitro study is preparatory to a clinical trial evaluating antibody-targeted chemotherapy in the treatment of bone marrow failure associated cancer.

The Les Nelkin Memorial Pediatric Oncology Research Laboratory
Johnson Liu, M.D. is the Section Head, Experimental Hematology/Oncology and directs The Les Nelkin Memorial Pediatric Oncology Research Laboratory. The Laboratory is designed as a lasting monument to an exceptional young man struck down in the prime of his life by Wilms tumor. The objective of the Nelkin Laboratory is to support world-class laboratory research into the mechanisms of childhood cancer with the clear mission to translate these discoveries into improvements in the treatment and prevention of childhood cancer.

The Nelkin Memorial Pediatric Oncology Research Laboratory enables the Division of Pediatric Hematology/Oncology and Stem Cell Transplantation to expand its research efforts, concentrating on translating laboratory science into clinical advances in the area of pediatric cancer.

Dr. Liu, Les Nelkin Professor of Pediatrics is an investigator of international caliber. The Les Nelkin Memorial Pediatric Oncology Research Laboratory will be housed in 4000 ft2 of modern and fully equipped laboratory space in the Institute for Medical Research of the North Shore - LIJ Health System and is adjacent to the Michael Neisloss Hematopoiesis Research Laboratory.