Funded Research
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A Novel Approach to Elicit Anti-tumor Immunity Against Acute Myeloid Leukemia
$500,000 Tower Senior Investigator Grant
Patients with acute myeloid leukemia (AML) have a relatively poor outcome, compared with those with acute lymphocytic leukemia (ALL), another major type of leukemia. AML patients are associated with a high risk of disease come-back. Currently, immunotherapies, which mobilize a patient’s own T cells to eliminate cancer cells, have proven effective against other leukemias, particularly ALL. However, currently available immunotherapy approaches have been less effective against AML. Recently, several biology studies have shown that stimulating endogenous transposable elements, namely, long-interspersed-element-1 (L1), can induce a strong anti-tumor immune response. Herein, our preliminary study in an AML mouse model showed that antagonizing a novel enzyme can promote L1 and stimulation of the immune system, blocking disease development. Dr. Li proposes that this new drug could be developed as an anti-AML therapy and tested either alone or combined with other immunotherapies in future clinical trials.
Ling Li, PhDCity of Hope -
Exploring DOCK2 Activation In Drug Resistance And Pathogenesis Of Chronic Lymphocytic Leukemia
$100,000 Tower Career Development Grant
Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adults— DOCK2 is a key protein in cell signaling pathways that contributes to the development and progression of CLL. Dr. Hasan’s research suggests that DOCK2 could be neutralized by an antibody called cirmtuzumab or inhibitors called ibrutinib/acalabrutinib.
In fact, combining the two may become the answer to treating CLL, and this TCRF-funded project will provide the research support necessary to make such a treatment possible, which would improve the quality of life of CLL and related blood cancer patients.
Md Kamrul Hasan, PhDUniversity of California, San Diego -
Uncovering the Scope of DFFB-Mediated Cancer-Acquired Drug Resistance
$100,000 Tower Career Development Grant
This research’s focus is on how to increase the durability of cancer treatment responses and prevent the emergence of drug resistance; specifically identifying new therapeutic targets and approaches which eradicate minimal residual disease that persists in patients after initial treatment responses. This work has the potential to reveal new therapies which will transform transient responses into cures for patients.
Matthew Hangauer, PhDUniversity of California, San Diego -
Novel Drug Targets for High Grade Serous Ovarian Cancer identified through Induced Pluripotent Stem Cell Modeling of Disease
$500,000 Tower Senior Investigator Grant
Faults in high risk genes cause high grade serous ovarian cancer (HGSOC). This cancer is often lethal in patients. Novel drugs are needed to improve treatment and patient outcomes. We plan to use cells from individuals carrying high risk genes to develop precision models of their disease and then cutting edge methods in genomics and functional screens to identify novel therapeutic targets that can be tested for their potential to treat patients with HGSOC. Ultimately we expected these studies will improve survival rates in patients that get HGSOC because they carry faulty genes.
Simon Gayther, PhDCedars-Sinai Medical Center -
Cold Atmospheric Plasma for the Treatment of NF1-related Peripheral Nerve Sheath Tumors
$100,000 Angie and Michael David Career Development Grant
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue sarcomas for which the only effective therapy is surgery and NF1 patients have a greater risk of developing these tumors from plexiform neurofibromas. These tumors are collectively known as Peripheral Nerve Sheath Tumors (PNSTs). One area of active research in plasma medicine is the use of cold atmospheric plasma (CAP) in treating tumors. In this proposal, we want to investigate the role of CAP in treating NF1-related PNSTs.
Brian Na, MDUniversity of California, Los Angeles -
Epigenetic control of stem cell plasticity in colorectal cancer development and recurrence
$100,000 Tower Career Development Grant
Colorectal cancer (CRC) is the second-most lethal cancer in the United States causing 50,000 deaths annually. Cancer is caused by alterations in genetic material called mutations, however correcting such changes remains unfeasible. Additionally, non-genetic structural and chemical changes are essential for cancer to gain aggressive growth potential and evading therapy. Although such non-genetic changes are essentially reversible using therapeutic drugs, details of how and when they occur during CRC progression remains unknown. Using cutting-edge human CRC and mouse model systems, we will characterize the non-genetic changes during CRC growth and identify novel factors that can be targeted for innovative therapies.
Unmesh Jadhav, PhDUniversity of Southern California -
Single Cell Spatial Analysis of DLBCL to Develop Biomarkers and Optimize CAR T Therapy
$100,000 Tower Career Development Grant
Recently we have discovered ways to reinvigorate the immune system to fight cancer. However, in immune cancers such as lymphoma, the line between cancer and the immune system is blurred. This presents an opportunity to learn how immune cells attack cancer under complex conditions, which is called the tumor microenvironment. I propose to use a spatial protein analysis technology to identify clues, not just in cancer cells but also in the embedded immune cells, that predict cancer outcomes. Further, I will study how genetically engineered anti-tumor immune cells operate in the tumor microenvironment to improve their efficacy.
Alexander Xu, PhDCedars-Sinai Medical Center -
The impact of alpha catenin loss on DNA repair defects in triple negative breast cancer
$500.000 Barry Rosenbloom, MD Senior Investigator Grant
Triple negative breast cancer (TNBC) is an aggressive and has a high death rate, especially in black women. We have found a gene marker that may make these tumors escape chemotherapy. Our research also shows that when this marker is not present, the tumor cells respond to a very specific type of cancer therapy. Also, there might be more immune cells that come into the tumor. Therefore, we wish to expand our research help better understand the role of this marker in breast cancer growth to improve treatment of this hard to treat form of cancer.
John Carpten, PhDCity of Hope -
Targeting Monoamine Oxidase A to Expand Cancer Immune Checkpoint Blockade Therapy
$500,000 Magnolia Council Senior Investigator Grant
Immune checkpoint blockade (ICB) therapies have revolutionized the treatment of many cancers; however, the existing ICB therapies can only benefit a small fraction of cancer patients, demanding an expansion of ICB therapies. Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain; small molecule MAO inhibitors (MOIs) have been developed and are clinically used for treating depression. This proposal aims to study MAO-A regulation of antitumor immunity and evaluate MAO-A blockade for cancer immunotherapy. The project has the potential to identify MAO-A as a new immune checkpoint and support repurposing MAOI antidepressants for cancer immunotherapy.
Lili Yang, PhDUniversity of California, Los Angeles -
Performance of hypermethylated circulating tumor DNA’s in colorectal cancer
$100,000 Rosen Cherney Tower Golf Tournament Research Grant
Measuring DNA produced by colorectal cancer (CRC) in blood (ctDNA) is a new method to detect return (recurrence) of CRC. We developed an in-house, blood-based ctDNA test that is less costly and easier to apply in practice. We will compare our ctDNA test’s performance to a commercial ctDNA test for detecting recurrence in patients who no longer have CRC and tumor growth or spread in patients with existing CRC. We will also analyze our test’s potential to predict recurrence in localized rectal cancer, which can be helpful to identify candidates who can be spared from unnecessary surgery (ostomy bags).
Jun Gong, MDCedars-Sinai Medical Center
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