TCRF
Funded Research

  • Discover Pathways Whose Inhibition Can Synergize With a PARP Inhibitor in Triple-Negative Breast Cancer
    $100,000 Irving Feintech Family Foundation Career Development Research Grant

    We want to develop a novel therapeutic approach for a subtype of aggressive breast cancer known as triple-negative breast cancer (TNBC) that lacks estrogen and progesterone receptors and does not over-express a protein called Her-2. We have learned a lesson from another type of breast cancer (BRCA mutant): In the presence of a drug that inhibits DNA repair (PARP inhibitor) these breast cancer cells often die. We hope to identify the Achilles heel of TNBC by making these cells sensitive to a PARP inhibitor, causing their death. We will discover the Achilles heel using a modern molecular biology technique called shRNA library screen. This technique delivers an inhibitor against every gene in the breast cancer cell population. Through a somewhat complicated method of selection, we will identify a pathway which, when inhibited, markedly enhances the ability of a PARP inhibitor to kill these breast cancers. Knowing the “killing” pathway, we will identify or synthesize a drug that can inhibit the pathway, and when combined with a PARP inhibitor, kills TNBC. Our approach has the potential to identify an entirely new way of treating this devastating cancer.

    Helene Marijon, MD
    Cedars-Sinai Medical Center
  • The role of lincRNAs in B-lymphoblastic leukemia pathogenesis and diagnosis
    $100,000 Irving Feintech Family Foundation Career Development Research Grant

    Major strides have been made in understanding cancers of blood cells (termed leukemia). However, recent scientific advances suggest that we do not yet understand the whole picture – new biological molecules that regulate how blood cells are made and renewed are being discovered. Here, we will test whether detecting these molecules can help diagnose or give information on prognosis to patients. We will also conduct experiments to see if these molecules are causally linked to leukemia and if they represent good targets for therapy.

    Dinesh Rao, MD, PhD
    University of California, Los Angeles
  • Antibody-interferon fusion proteins for treatment of B-cell lymphomas
    $100,000 Lakin Family Foundation Career Development Research Grant

    This two-part study aims to evaluate a new biologic agent for treatment of B cell non-Hodgkin lymphomas. The drug consists of two immune system proteins linked together through genetic engineering – an antibody that attaches to the surface of cancer cells, and interferon-alpha, which inhibits the growth of malignant cells. This antibody-interferon fusion thus targets the toxic protein directly to tumors. This treatment is highly effective against lymphoma in mice, and we now plan to: 1) Test the antibody-interferon fusion against human lymphoma cells in the laboratory, and 2) Design a Phase I clinical trial to begin testing in humans with lymphoma.

    Gataree Ngarmchamnanrith, MD
    University of California, Los Angeles
  • Discovery of novel classifications and therapeutic targets using several genomic sequencing approaches
    $100,000 Tower Career Development Grant

    Acute lymphocytic leukemia (ALL) is a fatal disease in 70% of adults and in most children who either relapse or do not go into initial remission. New therapeutic approaches are needed. We (Maya Koren-Michowitz/Koeffler) have spent a large amount of our academic careers treating these patients and looking for genomic abnormalities in their cells that might help us improve their therapies. Recently, we have utilized several new technologies called exon sequencing and distant pair-end whole genome sequencing (or gPET), as well as a second complementary technique, exon capture and DNA sequencing. Using these techniques, we will look at a selected group of ALL samples at diagnosis, remission and relapse to understand the full scope of genomic changes that occur in ALL. With that knowledge, we will interrogate a very large number of ALL samples to determine the clinical frequency and clinical significance of these alterations. Finally, we will use this knowledge to identify new therapeutic targets, and work with various industrial and academic entities to develop novel therapies, both for adult and pediatric ALL.

    Maya Koren-Michowitz, MD
    Cedars-Sinai Medical Center
  • Sec61β and platinum drug resistance
    $50,000 Hope Rosen Cancer Research Career Development Grant

    Platinum-based chemotherapy continues to be an essential component of the drug regimens given to patients with a variety of cancers including breast, colon, long, testicular and ovarian. Although most patients respond to treatment with tumor shrinkage initially, in many cases, the cancer comes back resistant. We have discovered a new mechanism involving a protein called sec61beta through which one can affect tumor cell resistance to the platinum drugs, as well as to a variety of other commonly used chemotherapeutics. By understanding this mechanism, we may potentially be able to modify it to increase chemotherapy sensitivity in a variety of cancers.

    Paolo Abada, MD
    University of California, San Diego
  • Towards developing novel biomarkers and therapeutic targets in castration-resistant prostate cancer
    $50,000 Tower Career Development Grant

    The objective of the project is to identify novel biomarkers for metastatic castration-resistant prostate cancer (mCRPC). Currently, radiographic imaging and serum prostate specific antigen (PSA) are the most common modalities used to track the course of mCRPC, but neither is believed to be an ideal surrogate for disease status. Preclinical data implicates signal transducer and activator of transcription 3 (STAT3) and prostate cancer stem cells (PCSCs) in prostate cancer pathogenesis. The project focuses on assessing these moieties in the peripheral blood of patients with mCRPC as an initial step towards Institutional Review Board (COH IRB 11004) approval to facilitate the proposed studies.

    Sumanta Kumar Pal, MD
    City of Hope
  • Novel understanding and treatment of Acute Leukemia
    $50,000 Tower Career Development Grant

    One of the major defects in acute leukemia is a block in differentiation preventing the young blast cells from becoming mature useful blood cells. As a result, the patient dies of infection, severe anemia, and hemorrhage. We believe that we have discovered one of the causes of this block in differentiation. By understanding this abnormality, we now have a new target that can be attacked therapeutically.

    Ahmed M. Aribi, MD
    University of California, Los Angeles
  • Thrombopoietin’s stabilization of Tensin2, a protein with migrational implications
    $50,000 Tower Career Development Grant

    The proposed research focuses on bone marrow stem cells that mature into the diverse range of cells found in the blood: white cells, important in defense against infection; red cells, which shuttle oxygen and carbon dioxide to and from all parts of the body; and platelets, essential in blood clotting in response to injury. Successful completion of the proposed work will advance our understanding of the intracellular events necessary for cell maturation and migration; such knowledge will aid in designing new strategies, when the normal machinery has faltered, to prevent leukemic and other cancer cell growth and metastasis.

    Andre Scott Jung, MD
    University of California, San Diego
  • Quercetin: A New Hepatocellular Carcinoma Prevention Paradigm
    $50,000 Tower Career Development Grant

    Chronic hepatitis C (HCV) is a global disease affecting more than 170 million people. Chronic carriers risk serious complications including liver cirrhosis, failure, and cancer. HCV is responsible for the recent liver cancer doubling in the U.S. Treatment options for chronically infected patients are limited, expensive, poorly tolerated, and frequently not effective.
    We have recently demonstrated the flavonoid Quercetin to inhibit HCV production in our lab. This represents a promising novel antiviral target for secondary prevention and an opportunity to address the large population of patients who are currently untreated and thus at higher risk of liver cancer.

    Nu Lu, PhD
    University of California, Los Angeles
  • Novel immunotherapies against chemotherapy refractory ovarian cancer
    $50,000 Tower Career Development Grant

    When ovarian cancer stops responding to chemotherapy, few options remain for patients. One approach which may prove beneficial involves harnessing the power of the immune system to fight this disease. Our proposed treatment involves training the patient’s own immune system to selectively target their tumor cells. This targeted approach should minimize side effects and provide a long lasting, self-renewing “drug” for the patient because of the property of immune cells to reproduce themselves. In addition, we intend to use sensitive PET scans to monitor the persistence of the immune cells and their interactions with the tumor.

    Arun Singh, MD
    University of California, Los Angeles

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