| Matches Found: 1746 |
| Career Development:Fellow |
| Vinay Tergaonkar, PhD - 2002 (Inactive) - 5391-02 |
|
| Salk Institute for Biological Studies |
| San Diego, CA US |
| ROLE OF I KAPPA B KINASE-2 (IKK2) IN LYMPHOCYTE DEVELOPMENT |
| Lymphomas arise as a result of uncontrolled proliferation of lymphocytes or failure of cells to die according to the predetermined developmental program for a particular cell type. NFB is one of the molecules whose controlled activity is required for normal growth of lymphocytes. Abnormally high levels of NFB are observed, and thought to contribute to, abnormal growth that occurs in leukemias and lymphomas. IKK2 is a key enzyme that is required to activate NFB. It has not been possible to define the role of IKK2 in the proliferation, maturation, and death of the normal immune system, because experimental animals that lack IKK2 fail to survive embryonic development. This project will make these investigations possible by creating a mouse that should be able to survive embryonic development, but will lack IKK2 in its blood cells. The availability of this experimental system will permit investigation of how the activity of NFB is modulated in normal development and in aberrant cells present in leukemia and lymphoma. |
|
| Career Development:Fellow |
| Karen Ross, PhD - 2002 (Inactive) - 5097-02 |
| Laboratory of Molecular and Cell Biology |
| National Institutes of Health |
| Bethesda, MD US |
| CHARACTERIZATION OF TWO ANAPHASE REGULATORS FROM YEAST |
| Errors that cause cells to inherit the wrong number of chromosomes are an early step in the development of many cancers, including adult T-cell lymphoma. Two factors important for accurate chromosome segregation are separins, which trigger chromosome separation, and securins, which first help separins enter the nucleus, but then inhibit separin activity until cells are ready divide. Using yeast as a model system, Dr. Ross will investigate how separins and securins perform these varied activities by studying the functions of different parts of these two proteins. She will then examine how securins help deliver separins to the nucleus. This project will help us to better understand an important step in the development of blood-related cancers. |
|
| Career Development:Scholar |
| William Tansey, PhD - 2002 (Inactive) - 1548-02 |
|
| Cold Spring Harbor Laboratory |
| Cold Spring Harbor, NY US |
| UNDERSTANDING PROTEOLYSIS OF THE ONCOPROTEIN TRANSCRIPTION FACTOR MYC AND HOW THIS IS PERTURBED IN LYMPHOMA |
| Myc is a protein that controls cellular growth. Elevated levels of Myc are known to contribute to a variety of human leukemias and lymphomas. Dr. Tansey and his co-workers have established that normal cells control Myc by destroying it soon after synthesis, but that this process is abnormal in lymphomas, leading to elevated levels of Myc in these tumor cells. This project is directed toward elucidating the mechanisms that cells use to control Myc destruction and how this process goes awry in cancer. The outcome of this investigation will help determine how abnormal Myc levels contribute to blood-related malignancies. |
|
| Career Development:Fellow |
| Elizabeth Sprague, PhD - 2002 (Inactive) - 5436-02 |
| Department of Biology |
| California Institute of Technology |
| Pasadena, CA US |
| STRUCTURAL STUDIES OF THE HERPES SIMPLEX VIRUS IMMUNOGLOBULIN G RECEPTOR |
| The herpes simplex virus makes two proteins, named gE and gI, that interact to form a complex that binds antibodies. The gE/gI protein complex binds antibodies in an unusual way, interfering with the body’s normal methods of attacking infections. Dr. Sprague will engineer cells to produce large amounts of the gE, gI, and antibody proteins. She will then purify and characterize these proteins, in order to determine the three-dimensional structures of the gE protein, gE/gI complex and gE/gI-antibody complex. These studies will reveal fine details about how the gE/gI complex interacts with antibodies, leading to a better understanding of how viruses subvert the immune system. |
|
| Career Development:Special Fellow |
| Eric Weiss, PhD - 2002 (Inactive) - 3112-02 |
| Department of Biochemistry, Molecular & Cell Biology |
| Northwestern University School of Medicine |
| Evanston, IL US |
| CORTICAL REGULATION OF CELL MORPHOGENESIS |
| This project concerns a fundamental problem in biology, how cells control their three-dimensional organization. The division and movement of single cells, cellular function within tissues, and embryonic development all require precise control of cell architecture. Loss of this control is an important feature of a number of major diseases, including cancer. Dr. Weiss will approach this problem in yeast using classical and novel genetic methods. He will pay particular attention to the influence of several enzymes upon cell shape. The specific pathways to be investigated are also used by human cells to direct the spatial organization of cellular processes. |
|
| Career Development:Fellow |
| Jun Sun, PhD - 2002 (Inactive) - 5071-02 |
| Department of Molecular & Experimental Medicine |
| Scripps Research Institute |
| La Jolla, CA US |
| Biologic Implications Of The Interaction Between Phospholipid Scramblase And C-abl Kinase |
| PLSCR1 is a newly identified protein, which is found in the membrane envelope that surrounds all cells. Its precise function remains unsettled, however it is likely to be involved in determining the characteristics of the cell surface and in controlling the survival of cells inside the body. Dr. Sun has observed that PLSCR1 interacts with another cellular protein, c-Abl. Alterations in c-Abl have been directly linked to a variety of human leukemias and other malignancies. The aim of this project is to elucidate molecular and cellular consequences of the interaction between PLSCR1 and c-Abl. Experiments will be carried out to determine how and why these proteins interact. Dr. Jun will then explore how the molecular interactions he has characterized might influence the proliferation and survival of malignant cells within the body. |
|
| Career Development:Fellow |
| Katherine Zahradka, PhD - 2002 (Inactive) - 5285-02 |
| Department of Gene Therapy |
| Mount Sinai School of Medicine |
| New York, NY US |
| MOLECULAR CHARACTERIZATION OF THE HEMANGIOBLAST |
| The earliest steps in the development of the vascular system involve the formation of both blood cells and the endothelial cells that will line the blood vessel walls. Previous investigations have indicated that blood and endothelial cells arise from a common precursor termed the hemangioblast. In this study, genes will be isolated from a population of cells believed to contain the hemangioblast. These genes will be analyzed to gain a better understanding of the initial formation of the vascular system as a whole and how these processes may potentially go awry during development of leukemia and lymphoma in the adult. |
|
| Career Development:Special Fellow |
| Ana Losada, PhD - 2002 (Inactive) - 3473-02 |
|
| Cold Spring Harbor Laboratory |
| Cold Spring Harbor, NY US |
| THE MECHANISM OF SISTER CHROMATID COHESION IN VERTEBRATE CELLS |
| The two copies of each chromosome, called sister chromatids, that arise from duplication of the genetic material must be held together until cell division occurs. The association between sister chromatids permits the recognition and repair of errors that occur during the copying process, and the orderly packaging of the genetic material. More importantly, it ensures that each chromatid goes to a different daughter cell. Premature separation of the sister chromatids results in abnormal chromosome distribution, a condition correlated with cancer and birth defects. Dr. Losada and co-workers have identified a protein complex, called cohesin, and have established that it is required for sister chromatid cohesion in vertebrate cells. The goal of this project is to understand how cohesins work at both cellular and molecular levels. |
|
| Career Development:Special Fellow |
| Cornelius Schmaltz, MD - 2002 (Inactive) - 3110-02 |
|
| Memorial Sloan-Kettering Cancer Center |
| New York, NY US |
| COOPERATION OF TRAIL AND OTHER CYTOLYTIC PATHWAY EFFECTORS IN BONE MARROW TRANSPLANTATION |
| TRAIL and a variety of related molecules mediate the way immune cells kill foreign cells as well as tumor cells. In bone marrow transplant (BMT) both pathways play an important role. Graft-versus-leukemia effect (GVL) is the advantageous attack of the transplanted immune cells on the leukemic cells. While graft-versus-host-disease (GVHD) is the unwanted attack of the transplanted immune cells on the patient’s own tissues. By using BMT and leukemia models in mice that are genetically altered to lack one or more of these molecules, Dr. Schmaltz will examine the role of these molecules in GVL and GVHD and endeavor to find ways to separate them. |
|
| Career Development:Scholar |
| Francisco Asturias, PhD - 2002 (Inactive) - 1434-02 |
|
| Scripps Research Institute |
| La Jolla, CA US |
| Structural Studies of Eukaryotic DNA Transcription Regulation |
| The abnormal expression and activities of various gene products underlie the aberrant growth of cancer cells. An important aspect of gene regulation is the control the expression of individual DNA sequences through the process termed transcription. The focus of this project is on providing a structural basis for understanding the regulation of DNA transcription in cells with nuclei. The goal is to provide a very detailed picture of how various components of the cellular transcription machinery interact with each other. The technique that Dr. Asturias will use is single-particle three-dimensional electron microscopy, a sophisticated technique for directly examining complexes of proteins. This structural information will provide insights into critical interactions involved in the regulation of gene expression. |
|
| Career Development:Special Fellow |
| Alexei Toutchkine, PhD - 2002 (Inactive) - 3427-02 |
|
| Scripps Research Institute |
| La Jolla, CA US |
| SPATIAL AND TEMPORAL CONTROL OF MAP KINASE PHOSPHORYLATION IN TRANSFORMATION AND METASTASIS |
| For several cancers, abnormal activation of the enzyme, MAP kinase, is central to the uncontrolled cell growth and migration that are the hallmarks of cancer. Paradoxically, the same protein is activated as part of the maturation of normal cells. Activation of MAP kinase can produce different effects depending on where in the cell it is turned on. Dr. Toutchkine we will compare the location and timing of MAP kinase activation in normal and cancer cells by developing a new MAP kinase 'reporter protein' that emits light when activated. This system will then be used to identify and characterize the roles of specific cell components in MAP activation. |
|
| Career Development:Scholar |
| Ali Shilatifard, PhD - 2002 (Inactive) - 1520-02 |
| Department of Biochemistry |
| Saint Louis University School of Medicine |
| Kansas City, MO US |
| THE ROLE OF TRANSCRIPTION FACTORS MLL AND ELL IN THE DEVELOPMENT OF HUMAN LEUKEMIA |
| The fundamental understanding of the role of molecular factors involved in the development of human malignancies is critical for our comprehension and treatment of human cancers. Dr. Shilatifard and collaborators have identified a family of proteins, designated ELL (eleven nineteen lymphoid leukemia). The first member of this family to be characterized, ELL, is associated with a gene, MLL (mixed lineage leukemia), which is found in acute human leukemia. The goal of this project is to decipher the molecular role of both ELL and MLL proteins in normal cellular growth regulation and during the development of acute myeloid leukemia. |
|
| Career Development:Special Fellow |
| Jeffrey Singer, PhD - 2002 (Inactive) - 3374-02 |
| Department of Molecular Biology, Cell Biology, and Biochemistry |
| Brown University |
| Providence, RI US |
| REGULATION OF THE G1/S TRANSITION IN MAMMALIAN CELLS BY TARGETED PROTEOLYSIS |
| A major regulatory step in cell proliferation is the commitment to entering the cell division cycle through several irreversible steps that lead to DNA synthesis. A particular set of proteins are synthesized and rapidly degraded in this part of the cell cycle. The cell cycle dependant synthesis of these proteins is accomplished by regulation of gene expression. Rapid degradation is regulated by a targeted-protein destruction system involving the small protein, ubiquitin. How the destruction of proteins regulates the G1/S transition in mammalian cells is poorly understood. Dr. Singer will investigate several proteins that are believed to play a key role in controlling protein degradation at this critical step in cellular proliferation. |
|
| Career Development:Fellow |
| Neil Shah, MD, PhD - 2002 (Inactive) - 5281-02 |
| Division of Hematology & Oncology |
| University of California at Los Angeles |
| San Francisco, CA US |
| MOLECULAR ASSESSMENT OF RESISTANCE MECHANISMS TO STI 571, A NOVEL BCR-ABL-SPECIFIC TYROSINE KINASE INHIBITOR. |
| The genetic alteration that gives rise to most, if not all, cases of chronic myelogenous leukemia is known. This mutation leads to the formation of a protein, designated Bcr-Abl, that is found only in leukemic, and not in normal cells. The drug, STI-571 (Gleevec) that antagonizes this protein is being tested in clinical trials, and appears to be well-tolerated and capable of leading to complete remissions. However, some patients treated with this drug do not respond dramatically, and in some cases become resistant. The goal of this project is to understand the mechanisms by which some leukemic cells become resistant to STI-571, with a view toward developing therapeutic interventions that can override resistance. |
|
| Career Development:Special Fellow |
| Calin Dumitru, MD, PhD - 2002 (Inactive) - 3519-02 |
| Department of Microbiology |
| Thomas Jefferson University |
| Philadelphia, PA US |
| The Role Of Tpl2 In Controlling Cytokine Expression In Activated Macrophages |
| Mutations in the mouse Tpl2 gene are associated with thymic lymphomas, and at the same time protect mice from septic shock. The Tpl2 gene product is required for the synthesis of two growth factors, IL-1beta and TNF-alpha, which start a cascade of cellular events that produce septic shock. In the absence of Tpl2, IL-1beta synthesis is decreased because it’s gene is not efficiently transcribed into an RNA copy, while the TNF-alpha defect in synthesis is novel, and involves a block to the movement of the RNA copy of the TNF-alpha gene to the protein synthesizing machinery. Dr. Dumitru will use Tp2-deficient mice to investigate how this protein regulates IL-1beta gene transcription, and elucidate the newly recognized mechanism by which TNF-alpha, synthesis is controlled. These insights into the normal activity of Tp12 will help us to understand better the progression of thymic lymphomas and other blood cell cancers. |
|
| Career Development:Scholar in Clinical Research |
| Aaron Rapoport, MD - 2002 (Inactive) - 2063-02 |
|
| University of Maryland |
| Baltimore, MD US |
| Autotransplantation Followed By Immunotherapy With Ex-Vivo Costimulated Autologous T-Cells: Using Chronic Myelogenous Leukemia (CML) As a Foundation for Developmental Studies In Multiple Myeloma (MM) |
| High-dose therapy followed by infusion of the patient’s own primitive blood cells (autologous stem cell transplants) has improved the response rates for patients with chronic myelogenous leukemia (CML) and multiple myeloma (MM). However, autologous transplants often fail due to the lack of immune cells (T-cells) capable of killing the leukemia or myeloma cells which remain after treatment. Experiments suggest that anti-leukemic and anti-myeloma T-cells do exist in patients with CML and MM but in an inactivated state. In this project, T-cells from patients with CML and MM will be activated in the laboratory and then returned to patients to better treat their disease. |
|
| Career Development:Special Fellow |
| Sheri Moores, PhD - 2002 (Inactive) - 3523-02 |
| Department of Cell Biology |
| Harvard Medical School |
| Boston, MA US |
| THE ROLE OF VAV PROTEINS IN BCR/ABL-MEDIATED LEUKEMOGENESIS |
| More than 90% of chronic myelogenous leukemia (CML) cases are caused by expression of an abnormal protein called BCR/ABL. There is evidence that BCR/ABL sends signals through another protein, Rac, that contributes to the abnormal properties of the leukemic cells in CML patients. Members of a family of proteins designated Vav, have been shown to activate Rac in other cells and have increased activity in BCR/ABL-expressing cells. Thus, Vav proteins may link BCR/ABL signals to Rac in CML cells. This study will attempt to induce a CML-like disease in mice that lack Vav proteins to determine whether Vav proteins are important for the development and progression of this leukemia. |
|
| Career Development:Scholar |
| Jonathan Graff, MD, PhD - 2002 (Inactive) - 1197-02 |
| Center for Developmental Biology |
| University of Texas |
| Dallas, TX US |
| Identification and Characterization of Genes That Regulate Cellular Proliferation and Blood Formation. |
| Leukemias, lymphomas, and myelomas occur in cells that have been programmed to differentiate into specific types of blood cells. The common feature of these cancers is that improperly maturing, malignant cells have lost growth control. The goal of Dr. Graff’s research is to design rational approaches to these deadly diseases, by providing a better understanding of the genes that control the transition from normal to cancerous. He and his collaborators will employ methods that they have devised to discover genes that might be important in this critical transition. Isolation of such molecules might provide new targets for the diagnosis, treatment, or prevention of hematological malignancies. |
|
| Career Development:Scholar |
| Anthony Capobianco, PhD - 2002 (Inactive) - 1298-02 |
|
| Wistar Institute |
| Philadelphia, PA US |
| Molecular Mechanisms of Notch Signaling in Neoplasia |
| At the cellular level, cancer can be viewed as an abnormality in growth control. Cancer cells arise as a result of mutations in genes that can promote cellular growth, or mutations that inactivate genes that suppress uncontrolled cellular growth. The consequence of these mutations is the disruption of the normal controls that govern cell growth. In T-cell acute lymphoblastic leukemia (T-ALL), the gene designated Notch1 becomes rearranged in a way that Notch is no longer properly regulated. Dr. Capobianco’s research is directed toward the elucidation of Notch’s function in intracellular pathways that respond to factors that normally control T-cell growth. He will try to determine how deregulation of these pathways can lead to leukemia. |
|
| Career Development:Special Fellow |
| Geeta Narlikar, PhD - 2002 (Inactive) - 3269-02 |
| Department of Biochemistry & Biophysics |
| The Regents of the University of California, San Francisco |
| San Francisco, CA US |
| MECHANISTIC INVESTIGATIONS INTO THE CHROMATIN REMODELING ACTIVITY OF THE HUMAN SWI/SNF COMPLEX |
| Specific information in DNA is transferred as RNA copies to the cellular protein synthesizing machinery, which then translate these transcripts into the appropriate proteins. A process called transcription is used to synthesize the RNA copy. However, the DNA in higher organisms is highly compacted into a structure called chromatin, which reduces the accessibility of DNA to the transcription machinery. One way this problem is overcome in the cell is by large protein assemblies that use energy from the breakdown of a high-energy compound, ATP, to disrupt chromatin structure. Dr. Marlikar’s research will address the issue of how these complexes affect chromatin structure, and, in turn, the expression of specific genes, a process that when improperly regulated can be manifested in leukemia and other cancers. |
|
