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Cancers of Childhood
Brain Tumors
Brain tumors are the most common solid tumor in children, with about 2,000 new patients diagnosed every year. At Children’s National Medical Center, we see nearly 10 percent of all brain tumor patients diagnosed in the United States and through a multidisciplinary team approach that includes neuro-oncology, neurology, neurosurgery, neuropathology, and neuro-radiology, we provide not only state-of-the-art clinical care, but perform cutting-edge research investigating the genetic causes, biology and new treatments of these tumors. The investigators studying brain tumors are Stephan Ladisch, MD, Tobey J. MacDonald, MD, Roger J. Packer, MD, Brian R. Rood, MD, and Stanislav Vukmanovic, MD, PhD.
Neuroblastoma
Neuroblastoma is the second most common solid tumor in children, and accounts for 50percent of all tumors diagnosed in children less than 2 years of age. At Children’s National Medical Center, we have an active clinical neuroblastoma program which employs state-of-the-art therapies, including stem cell transplantation, for the treatment of neuroblastoma patients. To complement the clinical program, we have an active research program to investigate the biochemistry, cellular biology, and immunology of tumor development and progression, and develop new therapies to complement conventional chemotherapy. The investigator studying neuroblastoma is Dr. Ladisch.
Leukemias and lymphomas
Leukemia is a form of cancer of any particular type of the white blood cells. Therapeutic approaches include irradiation and chemotherapy followed by bone marrow reconstitution. Naynesh R. Kamani, MD, and Brett J. Loechelt, MD, study immune reconstitution and the impact of CD34+ cell selection on engraftment, leukemia recurrence and immune recovery following transplantation.
Hemoglobinopathies
Hemoglobin is a molecule inside red blood cells that carries oxygen. Genetic disorders causing alterations in hemoglobin structure reduce the capacity of red blood cells to supply oxygen to tissues causing anemia. They also alter the physical properties of red blood cells making them more vulnerable to destruction and/or prone to induce damage of small blood vessels, potentially leading to stroke. The genetic disorders of hemoglobin include Sickle Cell Disease and Thalassemia. The investigators studying these diseases are Caterina P. Minniti, MD, Naomi L.C. Luban, MD, and Dr. Vukmanovic. Their research is described in the programmatic area of Hematology.
Autoimmune Disorders (Lupus and Diabetes)
The role of the immune system is to destroy foreign tissues while preserving the integrity of the host tissue and organs. In some cases the immune system fails in the task of preserving the tolerance to self, resulting in an autoimmune disease. The type of the immune disease depends on the tissue(s) attacked by the immune system. Sometimes the attack is global (for example in Lupus), and sometimes it is localized to a single tissue (such as Diabetes). The reasons and mechanisms for absence of tolerance to self can also be different, contributing to the diversity of autoimmune disorders. Dr. Vukmanovic and Olcay Y. Jones, MD, PhD, study the mechanisms of development, as well as means of therapeutical intervention in the mouse model of lupus. Dr. Kamani and Loechelt study the immune basis for chronic autoimmune diseases in humans and treatment of new onset type 1 diabetes with immune modulating agents.
Infectious Diseases
Infections with Human Immunodeficiency Virus (HIV) and Human Cytomegalovirus (HCMV) are clinically important because they either induce the state of secondary immunodeficiency or are especially frequent and difficult to resolve in immunodeficient patients. Hans M.L. Spiegel, MD, PhD, Larry D’Angelo, MD, and Tamara A. Rakusan, MD, PhD, are studying various clinical aspects of treatment of children with AIDS. Stephen Zeichner, MD, PhD, is investigating viral pathogenesis at the cellular level. Anamaris M. Colberg-Poley PhD, studies the pathogenesis of HCMV infection.
The laboratory of Dr. Zeichner, studies viral pathogenesis at a molecular level, with a focus on understanding the interactions of human immunodeficiency virus 1 (HIV-1) and Kaposi's sarcoma-associated herpesvirus (KSHV; Human herpesvirus-8, HHV-8) viruses and their host cells. The aim of the HIV research is to understand how host cell functions contribute to the maintenance of HIV latency, identifying cellular genes that help control HIV latency and identifying additional small molecule agents targeting the products of those genes. In addition, the influence of certain HIV gene products, such as Vpr, on host cell physiology and cell signal transduction pathways is studied. This work has additional implications for the pathogenesis and replication strategies of HIV. Studies of KSHV are focused on detailed kinetic description of the KSHV gene expression program and dissecting the KSHV gene expression program using inhibitors of KSHV replication that act a discrete points in the viral replication cycle. The effects of KSHV regulatory genes, such as KSHV Rta (ORF50), on the KSHV gene expression program, are also studied. Finally, in his clinical research, Dr. Zeichner studies pathogenesis of pediatric HIV disease.
Because of the widespread acquisition of resistance to antibiotics in the general population, testing old and new antibacterial coumpounds is of particular importance. The infectious diseases laboratories focus on the pharmacokinetics, safety and efficacy of antibiotics in collaboration with Stephen Soldin, PhD, in our GCRC Bioanalytic Core Laboratory and our newly NIH funded Pediatric Pharmacology Research Unit. Nalini Singh, MD, MBBS, is using molecular diagnostics for studying microbial resistance.
Primary Immunodeficiencies
Primary immunodeficiencies are arelatively rare group of disorders caused by mutations in genes participating in normal immune response. Consequently, some or all aspects of immune responses in affected individuals may be reduced or absent, resulting in chronic and repetitive infections. In the most severe cases long term treatment of choice is allogeneic bone marrow transplatation. Drs. Kamani and Loechelt study immune reconstitution in patients following hematopoietic stem cell transplantation and the impact of donor immunologic cell chimerism on immune recovery post-transplantation in children with primary immune deficiencies. Additional research investigations focusing on the impact of CD34+ cell selection on engraftment, leukemia recurrence and immune recovery following HSCT are underway.
Glycosphingolipid Storage Disorders (GSL)
GSL storage disorders are caused by a malfunction within the lysosomes, the recycling centers of the cell. Individuals with a GSL storage disorder have a genetic deficiency of one of the enzymes necessary to break down complex fatty/sugar molecules that then accumulate in body cells, particularly nerve cells within the brain, causing progressive neurodegeneration and death. GSL storage disorders include Tay-Sachs and Sandhoff diseases and GM1 gangliosidosis. The investigator studying the natural history and therapy for these diseases is Cynthia J. Tifft, MD, PhD.
Related Links
The Childhood Brain Tumor Foundation
www.childhoodbraintumor.org
The Leukemia and Lymphoma Society
www.leukemia.org
American Autoimmune and Related Diseases Association
www.aarda.org
Candlelighters Childhood Cancer Foundation National Office
www.candlelighters.org
National Childhood Cancer Foundation
www.curesearch.org
National Cancer Institute
www.cancer.gov/cancertopics/types/childhoodcancers
Medline
www.ncbi.nlm.nih.gov
Contact Information:
Stephan Ladisch, MD
Vice Chair for External Affairs, Department of Pediatrics
Children's Research Institute
Center for Cancer and Immunology Research
Children's National Medical Center
111 Michigan Avenue, NW
Washington, DC 20010
202-476-3898
202-476-3929 fax
sladisch@cnmc.org
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