Simon Gayther, PhD

Tower Senior Investigator Grant

Research Title: Novel Drug Targets for High-Grade Serous Ovarian Cancer identified through Induced Pluripotent Stem Cell Modeling of Disease

Cedars-Sinai Medical Center, Biomedical Sciences

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.


Brian Na, MD

Tower Career Development Grant

Research Title: Cold Atmospheric Plasma for the Treatment of NF1-related Peripheral Nerve Sheath Tumors

University of California, Los Angeles (UCLA)/Pediatric Hematology/Oncology

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue sarcomas for which the only effective therapy is surgery. Existing adjuvant therapy has produced lackluster results. Therefore, the development of better treatments is needed. One promising treatment is cold atmospheric plasma through reactive oxygen and nitrogen species generation. By exploring CAP as a therapeutic modality, we will define the mechanism by which CAP induces selectivity in cancer cell death and as a therapeutic delivery tool. We will describe the mechanism of CAP in cancer cell selectivity and examine the synergy between CAP and existing therapeutic modalities to improve outcomes.


Unmesh Jadhav, PhD

Tower Career Development Grant 

Research Title: Epigenetic control of stem cell plasticity in colorectal cancer development and recurrence

Norris Comprehensive Cancer Center, University of Southern California/Department of Stem Cell Biology and Regenerative Medicine

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 evade therapy. Although such non-genetic changes are essentially reversible using therapeutic drugs, details of how and when they occur during CRC progression remain 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.


Alexander Xu, PhD

Tower Career Development Research Grant 

Research Title: Single Cell Spatial Analysis of DLBCL to Develop Biomarkers and Optimize CAR T Therapy

Cedars-Sinai Medical Center, Cancer, Hematology/Oncology

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.


John Carpten, PhD

Tower Senior Investigator Grant

Research Title: The impact of alpha catenin loss on DNA repair defects in triple negative breast cancer

Keck School of Medicine of USC

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.


Lili Yang, PhD

The Magnolia Council Senior Investigator Grant

Research Title: Targeting Monoamine Oxidase A to Expand Cancer Immune Checkpoint Blockade Therapy

University of California Los Angeles

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.


Jun Gong, MD

Rosen-Cherney Tower Golf Tournament Research Grant

Research Title: Performance of hypermethylated circulating tumor DNA’s in colorectal cancer

Cedars-Sinai Medical Center

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).


Evanthia Roussos Torres, MD-PhD

Howard and Reva Colover Trust Career Development Research Grant

Research Title: Sensitizing the tumor immune microenvironment of breast cancer

Keck School of Medicine of USC

Breast cancer is the second leading cause of cancer-related death in women. Immunotherapies harness the body’s immune system to fight cancer, holding great promise to prevent recurrence and prolong survival. Immunotherapies have been less effective in patient’s with breast cancer in part, due to the recruitment of suppressive cells that prevent an anti-tumor effect. We will investigate strategies to decrease suppressive signals within the tumor, allowing anti-tumor signals to successfully eliminate tumor growth. We will also determine differences in suppressive signals between early versus metastatic breast cancers to improve response to immunotherapy for patients with all stages of disease.


Wenqi Wang, PhD

Cancer Free Generation Career Development Research Grant

Research Title: Harnessing the Hippo signaling pathway to counteract chemoresistance

University of California, Irvine (UCI)

Cisplatin-based chemotherapy has been widely used for treating a variety of solid tumors including breast, lung and ovarian cancers. Although initial therapeutic success is achieved, a number of tumors are found to be intrinsically resistant or gradually develop resistance to cisplatin treatment, which greatly limits its therapeutic potential. Notably, cisplatin belongs to the platinum compound family, which are known as the only heavy metal containing drugs used for chemotherapy. Our proposed research will focus on a growth-related signaling pathway, named the Hippo pathway in regulating heavy metal-induced stress response, which results in a unique mechanism accounting for the cisplatin-based chemo-resistance.



Jlenia Guarnerio, PhD

Tower Career Development Grant

Research Title: Identifying novel therapeutic targets in circular RNAs that bolster the sarcoma-protective microenvironment

Cedars-Sinai Medical Center

To identify circular RNAs abundantly expressed in Undifferentianted Pleiomorphic Sarcoma and illuminate how circRNAs catalyze cancer-promoting and drug-resisting conditions in the microenvironment surrounding tumor cells. In particular, we will study how circRNAs merge with RNAbinding proteins to powerfully modulate tumor cell secretions, which in turn forge a tumor-protective niche that renders many existing therapies ineffective against UPS. Finally, we will use newly developed molecular techniques to manipulate circRNAs in tumor cells, paving the way to design transcriptional therapies against UPS, and to use circRNAs to refashion the tumor microenvironment, rendering this intractable disease newly vulnerable to previously failed therapies.


Theodore Scott Nowicki, MD, PhD

Tower Career Development Grant

Research Title: Functional Epigenomics of Transgenic Cellular Immunotherapies for Cancer

University of California Los Angeles

Cellular immunotherapies, in which a patient’s immune system is genetically engineered to target cancer cells, are revolutionizing cancer treatment. However, these engineered cells do not always persist long-term in patients, which can lead to disease relapse. I propose that the DNA structure of these engineered immune cells changes over time, ultimately impairing the expression of receptors which target the cancer cells, and that these changes can lead to treatment failure. I will examine genetically engineered immune cells from patients receiving them for cancer treatment for this phenomenon, and correlate the DNA structural changes with engineered receptor expression and therapeutic response.


Soo Park, MD

Tower Career Development Grant

Research Title: Use of Metformin for Prevention of Clonal Progression to Therapy-Related MDS/AML

University of California San Diego

Clonal hematopoiesis describes a common pre-cancerous condition where blood stem cells gain mutations in cancer-associated genes that allow them to grow and expand abnormally. This condition occurs more frequently with increasing age and after chemotherapy for solid tumors where it is a strong risk factor for developing secondary blood cancers. Inflammation after chemotherapy exposure is known to favor proliferation of mutant blood stem cells. We are investigating the anti-inflammatory effects of metformin on mutant blood stem cell behavior and how the presence of clonal hematopoiesis impacts clinical outcomes in women who received curative-intent chemotherapy after surgery for advanced breast cancer.


Xiaochun Yu, MD, PhD

Xiaochun Yu, MD, PhD

Tower Senior Investigator Grantee

Research Title: ADP- riboslaytion and cancer therapy

City of Hope

Chemotherapy is a key approach to treat cancer patients, especially for the patients with invasive solid tumors. To date, more than 250 anti-cancer drugs have been used for chemotherapy. However, the most commonly used anti-cancer drugs for solid tumors non-specifically abolish DNA metabolism or cell division in growing cells. Thus, long term treatment with these anti-cancer drugs will cause severe side effects and chemo-resistance. Interestingly, a set of cancers harbor mutations that cause DNA damage repair defects. In this application, we plan to use this weakness of cancer cells to target DNA damage repair pathway, and develop novel chemotherapeutic approaches.


Steven Jonas, MD, PhD

Randi and Warren Grant Research Grant

Research Title: Nanosystems to accelerate clinical translation and generation of cellular immunotherapies

University California Los Angeles

For these patients, new treatments are being developed that recruit cells of the immune system to attack the cancer. To turn on these defenses, we need to deliver genetic instructions to about two hundred million immune cells, efficiently and safely. Unlike other strategies, these cells no longer need to come from the patients, who are already weakened. We have invented an engineering solution to do so and we are testing and optimizing it so that we can make this treatment widely available to patients and their doctors soon.


Yi-Tsung Lu, MD

The Cancer Free Generation Research Grant

Research Title: Predicting the metastatic risk of bladder cancer by cell-free DNA methylation sequencing

University of Southern California

Bladder cancer continues to cause significant mortality in the US due to the lack of reliable methods to identify high-risk patients who benefit from chemotherapy. We propose a study to characterize cell-free circulating DNA in the plasma for the purpose of creating a new noninvasive biomarker to identify patients with high-risk of recurrence. First, we will perform whole genome bisulfite sequencing to compare the methylation signatures between the patients who developed recurrence and those who did not. The identified differential methylation loci will be refined and then validated in a separate group of patients.


Martina Roos, PhD, PharmD

The Cancer Free Generation Research Grant

Research Title: Targeting AML Stem Cells using Novel Small Molecule Inhibitors of RNA Regulatory Proteins

University California Los Angeles

Acute myeloid leukemia (AML) is a devastating blood cancer were blood producing stem cells are damaged and become abnormally functioning leukemic stem cells (LSCs). To date, there is still no curative treatment targeting these aggressive LSCs. We identified novel compounds that inhibit important growth mechanisms of LSCs. In AML animal models and patient samples, these compounds decrease AML and improve survival. We will use rigorous experimental approaches to better understand the mechanism how these novel compounds kill LSCs. This project has a high potential to develop a new class of drugs for precision AML therapy.


Michael Karin PhD

Michael Karin, PhD

Tower Senior Investigator Grantee

Research Title: Using Oxaliplatin to improve the response to PD-1/PD-L1 blockade

University California San Diego

Immune checkpoint inhibitors had revolutionized cancer treatment. The most versatile such drugs are antibodies that target a receptor molecule called PD-1 or its ligand PD-L1. Although effective in many cancer types, response rates to these drugs rarely exceed 20-30%, necessitating the search for agents that synergize with PD-1/PD-L1 blockers. Using mouse models, we found that the conventional chemotherapeutic drug oxaliplatin has the unique ability to greatly enhance the response to PD-1/PD-L1 blocking antibodies. We will investigate how oxaliplatin increases the effectiveness of PD-1/PD-L1 blockers and will validate these findings in human lung cancer through a Phase I/II clinical study.


Joshua Sasine, MD

Joshua Sasine, MD

Tower Cancer Research Foundation Grant

Research Title: Eph/Ephrin Signaling Regulates Multiple Myeloma in the Bone Marrow Vascular Niche

University California Los Angeles

Sponsor: John Chute, MD

Multiple Myeloma is the second most common blood cancer. It arises out of plasma cells, whose normal function is to make antibodies to fight infections. Although in recent years the treatment has become more effective, it remains essentially incurable. One unique aspect of the disease is the close ties to the normal bone marrow cells, specifically the blood vessel cells. Without signals from these cells the cancer dies. We don’t know which signals are the most relevant; our experiments are designed to discover that. This could form the basis for new treatments designed to disrupt these pathways to benefit patients.


John Paul Shen, MD

John Paul Shen, MD

The Cancer Free Generation Research Grant

Research Title: Synthetic Lethal Networks to Guide Precision Oncology in GI Tumors

University California San Diego

Sponsor: Trey Ideker, PhD

Cancer cells have many mutations- that is what makes them cancer. Recently it has become clear every cancer patient’s tumor is unique; like snowflakes, cancer cells appear similar from a distance, but when inspected closely no two are exactly the same. This research proposal attempts to better understand how each tumor is different, so that in the future oncologists will be able to pick the right drugs for each unique patient and tumor. Specifically, I am looking to find weaknesses in the cancer cell, so that newer drugs will be able to kill cancer cells while sparing heathy cells.


Anusha Kalbasi, MD

Anusha Kalbasi, MD

Tower Cancer Research Foundation Grant

Research Title: Developing a Neoadjuvant Platform to Study Macrophage-Driven Resistance
to Immunotherapy in Sarcoma

University California Los Angeles

Sponsor: Antoni Ribas, MD, PhD

Immunotherapy is an exciting development in cancer treatment, but has not yet made its mark in sarcoma. The resistance of sarcoma to immunotherapy might be related to the presence of macrophages –a type of immune cell. Here, we aim to understand why sarcomas are full of macrophages, and how macrophages impede the immune system. We will determine how radiation therapy, which is commonly used for patients before surgery, affects these phenomena. Our ultimate goal is to design clinical trials to test drugs targeting macrophages in combination with radiation to make immunotherapy relevant for sarcoma.


Dechen Lin, PhD

Dechen Lin, PhD

Tower Cancer Research Foundation Grant

Research Title: Modeling Super-Enhancers in Barrett’s esophagus-associated neoplastic evolution

Cedars-Sinai Medical Center

Sponsor: H. Phillip Koeffler, MD, PhD

With the help of medical research, the incidences and mortalities of many common cancers (e.g., those from breast, lung and colon cancers) are dropping significantly in US. However, as one of the deadliest malignancies, esophageal carcinoma (EAC) has strikingly risen in incidence (> 600% during the last four decades in USA), with the five-year survival of only 16%. Although Barrett’s esophagus (BE) has long been regarded as a precursor lesion of EAC, no effective preventive strategies is available. Better characterization of EAC pathogenesis and its evolution from BE is greatly needed to decrease the impact of this deadly cancer.


Michael F. Press, MD, PhD

Jessica M. Berman Memorial Fund Senior Investigator Grant

Research Title: Polo-like Kinase 4 as a Regulator of Cytokinesis and as a Target for Cancer Therapy

University of Southern California

Polo-like kinase 4 (PLK4) regulates duplication of each cell’s centrosome, which facilitates movement of duplicated chromosomes to opposite poles in dividing cells. Without two centrosomes cells cannot divide; hence preventing cancer cell duplication. We have also found that PLK4 controls a final step in cell division, known as cytokinesis. We are part of a research collaboration that has developed a new drug, CFI-400945, which inhibits PLK4 activity. Our proposal seeks support to identify biomarkers that predict which cancers cannot complete cell division when PLK4 function is inhibited and which cancers, like normal cells, can complete cell division.


Guo-Min Li, PhD

Tower Senior Investigator Grantee

Research Title: Targeting Mismatch Repair System for Cancer Therapy

University of Southern California

Despite decades of extensive studies in cancer research, cancer is still the number 2 leading cause of death in the United States. The major problem is that individual cancers display distinct genetic abnormalities, and none of the known treatments and their combination can effectively deal with these abnormalities. We have recently created a mutant DNA repair protein that irreversibly binds to cancer cell-specific DNA errors during cancer growth, leading to cell death. This application aims to develop this mutant DNA repair protein into an effective drug for cancer therapy.


Adam Burgoyne, MD, PhD

Tower Cancer Research Foundation Grant

Research Title: Dual PI3K and BRD4 Inhibition as a Novel Therapeutic Strategy for Hepatocellular Carcinoma

University of California, San Diego

Sponsor: Donald L. Durden, MD, PhD

Liver cancer is the second most common cause of cancer death worldwide, but the sole FDA-approved drug for liver cancer prolongs life for only 2-3 months and has significant side effects. While most anti-cancer drugs have a single target, we are investigating a novel drug, SF1126, that simultaneously targets two proteins (PI3K and BRD4) that are overactive in liver cancer, and our experiments demonstrate that it is efficacious and well tolerated. We are studying the mechanism whereby SF1126 kills liver cancer cells and are actively pursuing the use of dual PI3K/BRD4 inhibitors in clinical trials in liver cancer patients.


Kate Lawrenson, PhD

The Cancer Free Generation Research Grant

Research Title: Identification and Functional Analysis of PAX8 Binding Site Mutations in Ovarian Cancer

Cedars-Sinai Medical Center

Sponsor: Ben Berman, PhD

Epithelial ovarian cancers (OC) are highly lethal tumors, but treatment options are limited, largely because our poor understanding of the biology of OC development has hindered the development of new drugs. Recent investigations in our laboratory and others identified the PAX8 gene as a major driver of OC, regulating the expression of key genes to promote tumorigenesis. The goal of this proposal is to understand how DNA mutations impact PAX8-dependent control of target gene expression to promote cancer development. The idea is that by understanding pathways upstream of cancer gene expression we can identify much-needed new therapeutic targets for OC.


Mina Nikanjam, MD, PhD

The Magnolia Council Research Grant

Research Title: Development of a Novel dCK Inhibitor for Leukemia and Lymphoma using PET Imaging

University of California, Los Angeles

Sponsor: Caius Radu, MD

DI82 is a new potential chemotherapy drug which can kill cancer cells by preventing them from making new DNA. The project will look at drug levels in the blood, tumor, and other parts of the body using an imaging machine (PET). The drug will be tested in mice in combination with two other drugs to determine how well they work together to kill tumor cells. This information will be used in a model to predict how much drug to give patients in future human studies.


Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute


Jack Mishkin Discovery Fund for Mesothelioma Research

Research Title: Discovery Fund


With scientific excellence and an ambitious vision, the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute is giving hope to patients with mesothelioma. With Tower’s support, Cedars-Sinai team members will collaborate across disciplines to investigate how mesothelioma begins, how it grows, and how to halt its progression. Team members will conduct research that spans the continuum - from novel laboratory explorations, to translational experiments, to clinical trials that test the safety and efficacy of new interventions for the prevention and treatment in humans. Clinical scientists and basic scientists will submit proposals and, after a rigorous peer-review process by the multi-disciplinary committee, a winning project(s) will be selected.


Richard J. Pietras, M.D., Ph.D.


Jessica M. Berman Memorial Fund Senior Investigator Grant

Research Title: Next-Generation Estrogen Receptor Downregulators for Breast Cancer Therapy


Despite remarkable improvements in treatment options, development of endocrine resistance is one reason that breast cancer is the second most frequent cause of cancer death in women. In most cases, estrogen receptor (ER) is present in these resistant tumors, and in many ER continues to regulate tumor growth. This project aims to develop a new clinical-translational strategy to address this challenge and promote patient survival. Dr. Pietras plans to develop a new generation of selective ER downregulators (termed SERDs) with the proper biologic/pharmacologic profile to be used as therapeutics for endocrine-sensitive and -resistant cancers in clinic.


Phillip Koeffler, M.D.


Michele and Ted Kaplan Family Senior Investigator Grant

Research Title: Synthetic Lethal Drug Discovery In Triple Negative Breast Cancer

Cedars-Sinai Medical Center

PARP inhibitors are promising new drugs for a subset of breast and ovarian cancers. However, as single agents PARP inhibitors show little activity in triple-negative breast cancer (TNBC). Dr. Koefler will use a TNBC cell model to evaluate the effect of single gene mutations on the response to PARP inhibition. Mutations conferring sensitivity will be further tested in cell lines, animal models, and TNBC patients. Based on our findings, Dr. Koefler will develop an assay to evaluate PARP sensitivity in clinical samples. The study will provide valuable insights that can be translated into biomarkers for patient selection, and new drug combination therapies.


John Kyung Lee, M.D.


The Irving Feintech Family Foundation Research Grant

Research Title: Targeting Myc Oncoproteins in Advanced Prostate Cancer


Mentor: Owen N. Witte, M.D.

Advanced prostate cancer is a deadly disease with limited treatment options. Two members of the Myc family of cancer genes named c-Myc and N-Myc are active in the main types of lethal prostate cancer - castration-resistant prostate adenocarcinoma and small cell neuroendocrine prostate cancer. In this work, Dr. Lee will clarify the biologic functions of c-Myc and N-Myc in two unique prostate cancer models developed from normal human prostates. Dr. Lee will take advantage of these models of advanced prostate cancer to find new therapies and evaluate a promising inhibitor that directly targets the activity of N-Myc in cancer cells.


Christopher Seet, M.D.


The Magnolia Council Research Grant

Research Title: Identifying Novel Mechanisms of Immune Evasion in Acute Myeloid Leukemia


Mentor: Gay M. Crooks, M.D.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults, and new treatment approaches are urgently needed. Immunotherapy has emerged as a safe and effective treatment for certain solid tumors, however the development of effective immunotherapies for AML requires a better understanding of the mechanisms by which leukemia evades the immune system. AML is associated with selective dysregulation of antigen presenting cells (APCs), which are a vital component of anti-tumor immune responses. The study will investigate mechanisms by which leukemia cells interfere with APC development with the goal of identifying novel immunotherapeutic targets in AML.


Daniel Sanghoon Shin, M.D.


The Cancer Free Generation Research Grant

Research Title: Regulation of PD-L1/L2 Expression in Melanoma


Mentor: Antoni Ribas, M.D. Ph.D.

The field of immuno-oncology has evolved over the past century, however, its therapeutic application to fight cancer has just begun with recent approval of new immunotherapy drugs in 2014. Anti-PD-1 antibodies produce unprecedented long lasting responses for patients with advanced melanoma and advanced lung cancer, it is expected to be approved for many other cancer types. Dr. Shin will study the regulation of PD-L1/L2 expression in response to interferons which will be highly relevant to understanding the response and resistance from anti-PD-1/L-1 antibody therapy and its great potential to develop an assay or identify bio-markers to predict the response.


Siwen Hu-Lieskovan, M.D., Ph.D.

The Katz Family Foundation Research Grant

Research Title: Double Immune Suppression Blockade to Treat Melanoma

Mentor: Antoni Ribas, M.D., Ph.D.
The success of tumor immunotherapy for the treatment of melanoma is limited by the presence of intratumoral immune suppressive cells. Our preclinical animal study showed a small molecule inhibitor of key myeloid cell receptor called CSF-1R would cripple the immune suppressive myeloid cells and improve the antitumor activity of effector immune cells. This allowed us to partner with Plexxikon to provide the CSF-1R inhibitor PLX3397 and Merck to provide the anti-PD-1 antibody MK-3475. We propose a phase 1 dose-escalation study to combine these two drugs, in patients with metastatic melanoma. We will do correlative studies to test mechanism of combinatorial effects.


Chintan Parek, M.D.

The Cancer Free Generation Research Grant

Research Title: Role of the Long Noncoding RNA DANCR in T Cell Acute Lymphoblastic Leukemia

Children’s Hospital of Los Angeles
Mentor: Alan Wayne, M.D.

T cell leukemia (T-All) is a type of blood cancer that affects children and adults. Newer treatments are urgently needed, as 20% of children and 50% of adults with T-ALL cannot be cured. Our research focuses on a recently discovered gene called DANCR, which is present at abnormally high levels in T leukemia cells. We have found that DANCR promotes the growth of leukemia cells. We are currently studying how DANCR promotes this growth of leukemia cells. These studies could ultimately lead to the development of new anti-DANCR treatments for leukemias.


Giridharan Ramsingh, M.D.

The Magnolia Council Research Grant

Research Title: Hematopoietic Stem Cell and Progenitor Cell Senescence and Therapy Related Acute Myeloid Leukemia

Mentor: Preet Chaudhar, M.D., Ph.D.
Patients with cancer are frequently treated with chemotherapy and/or radiation therapy. A small subgroup of these patients develops a type of leukemia called Therapy-related Acute Myeloid Leukemia (tAML) as a complication. It is a deadly disease with more than 90% of the patients dying within 5 years. Based on our recent work, we think the chemotherapy exposure to normal blood stem cells causes the stem cell to undergo rapid aging and the aged stem cells turn into cancer. The proposed study is to test this idea and in the process to discover how aging of blood stem cells causes leukemia.


Patricia A. Young, M.D.

TThe Irving Feintech Family Foundation Research Grant

Research Title: Molecular and immunologic correlates of responses to anti-CD 19 chimeric antigen receptor T cell therapy

Mentor: John M. Timmerman
CD 19 is a protein on the surface of B cells and serves as a potential target in advanced non-Hodgkin lymphomas and leukemias. One experimental treatment has been anti-CD 19 chimeric antigen receptor (CAR) T cells, which uses the patient’s T cells to engineer an anti-CD 19 portion to specifically recognize and kill CD 19-expressing cells. A clinical trial using anti-CD 19 CAR T cells will be implemented at UCLA in the summer of 2014. We plan to: 1) initiate a phase I clinical trial using transfer of engineered T cells, and 2) perform laboratory studies to improve upon and understand the mechanisms of this treatment.


Lihua Elizabeth Budde, M.D., Ph.D.

The Irving Feintech Family Foundation Research Grant

Research Title: Optimizing Adoptive Immunotherapy Using Anti-CD22 Chimeric Antigen Receptor Redirected T-C ells for Lymphoma

City of Hope
Mentor: Stephen Forman, M.D.
Most patients with lymphoma are not cured with conventional therapy. New treatment is urgently needed. This study proposes a novel strategy of inserting two genes into a patient’s own immune T cells. One gene will enable these cells to recognize and kill lymphoma cells; the other will serve as a cell self-destruct mechanism that activates on demand to eliminate modified T cells. Dr. Budde describes ways to generate these modified T cells and test the feasibility of using them in mice and then in a clinical trial. Dr. Budde believes that our treatment has the potential to cure lymphoma patients in the future.


Hyung C. Suh, M.D., Ph.D.

The John C. Hall Memorial Research Grant

Research Title: The role of BCOR in Normal Hematopoiesis and Hematopoietic Transformation

UCLA/Cedars-Sinai Medical Center
Mentor: H. Phillip Koeffler, M.D.
Acute Myeloid Leukemia (AML) and myelodysplastic syndrome (MDS) are characterized by increased cell proliferation and a block in differentiation preventing young cells from becoming mature useful blood cells. Transcription factors which govern the development and function of blood cells are frequently mutated in AML. We and others recently found mutations in the transcriptional co-repressor BCOR in AML and MDS. This study will use tissue culture studies and a murine model system to explore the function of BCOR in normal blood cell development and malignant transformation. These studies will broaden our understanding of AML/MDS and may lead to the development of novel therapeutics for these diseases.


Deborah Jean Lee Wong, M.D., Ph.D.

The Magnolia Council Research Grant

Research Title: Targeting ERK for Metastatic Melanoma

Mentor: Antoni Ribas, M.D., Ph.D.
There are very few effective treatments for metastatic melanoma. In most cases, even if treatments are initially effective, the melanoma adapts and becomes resistant to the therapy. ERK inhibitors are a new class of treatments that are being tested in patients with metastatic melanoma. This study will identify how melanoma develops resistance to ERK inhibitors. This will help us better understand how these drugs work and which melanoma patients would benefit the most from them.


Afsaneh Barzi, M.D., Ph.D.

Research Title: Tumor Heterogeneity and Resistance to HER2 Therapy in Gastric Cancer

Despite the success of targeted drugs in cancer care, patients frequently develop resistance to these drugs. This may be due to intra-tumor heterogeneity and the existence of genomically diverse cells within a single tumor. In theory, the cells that do not respond to the targeted drug will expand and become the dominant cell population in a tumor. Using a novel experimental and computational approach, we will infer tumor cell ancestry and measure intra-tumor heterogeneity in HER2 positive stomach cancers. We will determine whether intra-tumor heterogeneity predicts response to Herceptin and will identify biomarkers that are associated with treatment resistance.


Michael Choi, M.D.

The Magnolia Council Research Grant

Research Title: Inhibition of Wnt signaling to treat Leukemic Stem Cells: A Drug Development Proposal

Wnt signaling promotes the growth and development of many types of cancers, including colon cancer, multiple myeloma, and chronic lymphocytic leukemia (CLL). Furthermore, this pathway is highly active in cancer stem cells. Unfortunately, there are no potent and specific Wnt inhibiting therapies that are currently available. Agelastatin A is a naturally occurring compound that may fill this need. We plan to fully determine its activity in leukemia stem cells, and to perform the preclinical studies needed before ultimately bringing this promising compound to the clinic.


Helene Marijon, M.D.

The Irving Feintech Family Foundation Research Grant

Research Title: Discover Pathways Whose Inhibition Can Synergize With a PARP Inhibitor in Triple-Negative Breast Cancer

Cedars-Sinai Medical Center
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.


Dinesh Rao, M.D., Ph.D.

The Irving Feintech Family Foundation Research Grant

Research Title: The role of lincRNAs in B-lymphoblastic leukemia pathogenesis and diagnosis

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.


Gataree Ngarmchamnanrith, M.D.

The Lakin Family Foundation Research Grant

Research Title: Antibody-interferon fusion proteins for treatment of B-cell lymphomas

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.


Maya Koren-Michowitz, M.D.

Research Title: Discovery of novel classifications and therapeutic targets using several genomic sequencing approaches

Cedars-Sinai Medical Center
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.


Paolo Abada, M.D.

The Hope Rosen Cancer Research Grant

Research Title: Sec61β and platinum drug resistance

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.


Sumanta Kumar Pal, M.D.

Research Title: Towards developing novel biomarkers and therapeutic targets in castration-resistant prostate cancer

City of Hope
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.


Ahmed M. Aribi, M.D.

Research Title: Novel understanding and treatment of Acute Leukemia

Division of Hematology Oncology
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.


Andre Scott Jung, M.D.

Research Title: Thrombopoietin’s stabilization of Tensin2, a protein with migrational implications

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.


Nu Lu, M.D.

Research Title: Quercetin: A New Hepatocellular Carcinoma Prevention Paradigm

Division of Hematology Oncology
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.


Arun Singh, M.D.

Research Title: Novel immunotherapies against chemotherapy refractory ovarian cancer

Division of Hematology Oncology
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.


Robert W. Chen, M.D.

Research Title: Using SiRNA to CCNDI to Overcome Chemoresistence in Mantle Cell Lymphoma

City of Hope
Beckman Research Institute
Mantle cell lymphoma (MCL) is a rare and difficult lymphoma to treat. Standard treatment involves aggressive combinations of chemotherapy which often does not lead to long term survival. In the laboratory, scientists have been experimenting with using synthetic RNAs to silence specific genes know to be important in cancer cell survival. These synthetic RNAs are called SiRNA. Cyclin D1 is a specific gene known to be important in MCL biology. We will use SiRNA designed to silence cyclin D1 to improve the efficacy of standard chemotherapy in the treatment of MCL.


Herbert A. Eradat, M.D., M.S.

Research Title: Defining the Molecular Correlates that Determine Activity of Pan-PIM Inhibitor, SGI-1776

Division of Hematology Oncology
PIM kinases are oncogenes that are known to cause lymphomas. Our laboratory was the first to show that PIM-1 predicts shorter survival in aggressive lymphomas and we are currently conducting the first trial of a pill that inactivates PIM kinases. The core of this grant proposal is defining the molecular characteristics that will determine the activity of the PIM inhibitor SGI-1776 in lymphomas. In addition, we will test another target (cyclin D1) for its ability to collaborate with PIM kinases in causing lymphomas. This research may lay the foundation of novel combination treatment strategies.


Edward Kaverlerchik, M.D.

Research Title: Targeting CML Stem Cells with a Small Molecule Wnt-Signaling Inhibitor

Moores Cancer Center
Hematopoietic stem cells (HSC) are responsible for life-long blood production. When HSC acquires chromosomal derangement BCR-ABL their capacity to become diverse blood cells is altered, leading to expansion of white blood cells causing chronic myeloid leukemia (CML). BCR-ABL inhibition with oral drugs can hold the disease. Many patients demonstrate BCR-ABL resistance that leads to acquisition of new mutations in the HSC daughter cells and progression to acute leukemia stages - the Blast Crisis. Activation of Wnt-signaling pathway is critical for progression. We will test novel small-molecule Wnt-signaling inhibitor MCC-301 and analogs for their capacity to kill BC CML cells.


Eddie Garon, M.D.

Research Title: Correlation of Pancreatic Adenocarcinoma Molecular Profile with Response to Therapeutics

David Geffen School of Medicine
Division of Hematology Oncology
Will correlate gene profile in pancreas cancer cell lines and human specimens with treatment response.


Amir Goldkorn, M.D.

Research Title: Targeting Prostate Cancer Stem Cells with Telomerase Interference

Norris Comprehensive Cancer Center
Section of Genitourinary Oncology
Will examine prostate cancer stem cells which may respond differently to therapy than the differentiated cancer cells, and attempt to determine their vulnerability to the target telomerase (increases chromosome size and thus extends cell longevity.)


David Kim, M.D.

Research Title: Pim-1 in Mantle Cell Lymphoma: A Novel Therapeutic Target

Division of Hermatology Oncology
Doing studies to determine the importance of the oncogene Pim-1 in the pathogenesis of some cases of mantle cell lymphoma. Pim-1 may also be a therapeutic target.


Fariborz Mortazavi, M.D.

Research Title: Transcriptional Regulation of p120-catenin in Non-Small Cell Lung Cancer

Wadsworth VA, Los Angeles
Examining reasons for low levels of a novel catenin (p120 catenin) in non-small cell lung cancer. These low levels are associated with a poor prognosis. Catenins are important for normal cell-cell interactions and adhesions.


Richard Schwab, M.D.

Research Title: Anti-Neu5c Antibodies for Breast Cancer Detection

Moores Cancer Center
Early diagnosis of breast cancer with mammograms saves lives. Unfortunately, mammography is not as effective in women younger than 50. New tests that work in women of all ages are needed. Research has found a special type of sugar, called Neu5Gc, in breast cancer. Cancer, and our bodies, are unable to make this sugar, but it is plentiful in the diet and can be absorbed when eaten. Once incorporated into breast cancer cells this abnormal sugar causes a reaction by the patient’s immune system. This project will examine this reaction as a potential new test to diagnose breast cancer.


Saskia Gueller, M.D.

Research Title: Novel Gene Discovery and Classification for Mantle Cell Lymphoma

Cedars-Sinai Medical Center
Division of Hematology Oncology
The abnormal genes that cause mantle cell lymphoma (MCL) are poorly identified. Recently, an extremely robust technology has become available: 500K SNP chips. This glass platform allows examination of 500,000 sites in the human genome permitting us to study almost every gene in the cell. These chips, therefore, allow identification of genes that are amplified or deleted or have probable small mutations. Examining a large number of samples and associating the genetic abnormalities with the clinical data will permit us to develop new diagnostic subcategorization of this heterogeneous group of diseases, provide prognostic indicators for the patient and physicians, and identify targets for small molecule therapy. Because of its ease and robustness, the 500K SNP chip may become the standard of care for diagnosis, prognosis, and monitoring progession of MCL, as well as other malignancies.


Zev Wainberg, M.D.

Research Title: Inhibiting Src in Colorectal Cancer: Characterization and Identification of Molecular Biomarkers

Division of Hematology Oncology
Despite recent progress, colon cancer remains the second leading cause of cancer death in the United States. Over the last several years new therapies, known as “targeted therapies” have emerged which are offering patients the hope of improved outcomes with fewer side effects. This proposal is based on determining which patients with colon cancer would benefit from the use of drugs that block a gene known as Src. We will do a series of experiments in colon cancer cells and gene chips to define a patient group that will respond to these drugs before proceeding into a clinical trial.


Norihiko Kawamata, M.D.

Research Title: MDS - Novel Gene Discovery and Classification

Cedars-Sinai Medical Center
The abnormal genes that cause “preleukemia” (myelodysplastic syndrome, MDS) are poorly identified. Recently, an extremely robust technology has become available: 500K SNP chips. This glass platform permits us to examine 500,000 sites in the human genome to determine if abnormalities exist in almost every gene in the MDS cells. These chips, therefore, allow us to identify genes that are amplified or deleted or have probable small mutations. Examining a large number of MDS samples and associating the results with clinical data will permit us to develop new diagnostic subcategorization of this heterogeneous group of diseases, provide prognostic indicators for the patients and their physicians, and identify targets of small molecule therapy. Because of its ease and robustness, the 500K SNP chip may become the standard for diagnosis, prognosis, and monitoring progression of MDS, as well as other malignancies.


William D. Tap, M.D.

Research Title: Myelodysplastic Inhibition of Protein Farnesylation: A Promising and Potentially Unifying Treatment Modality in Sarcomas

Division of Hematology Oncology

Sarcoma is a rare form of cancer that affects individuals of all ages. Its diagnosis often carries a poor prognosis, as the benefit of traditional chemotherapy has been maximized. It is critical that we discover and apply new, more efficacious therapies. Recently, in our laboratory, we have discovered that Sarcoma cells are sensitive to a novel compound that blocks the cancer’s ability to grow and propagate. Currently, we are pursuing this compound as a treatment for patients with Sarcoma. In addition, we are using it as a scientific tool to help us unravel the molecular intricacies of this deadly disease.


Vincent Chung, M.D.

Research Title: Targeted Therapies in Pancreatic Cancer: A New Era of Treatment

City of Hope National Medical Center
Medical Oncology
Cancer of the pancreas is the fourth leading cause of cancer-related death. Approximately 32,180 new cases are anticipated in 2005, with 31,800 expected deaths and a median overall survival of only 6 months for cancer that has spread. Our traditional chemotherapy has not been able to significantly prolong life. Cancer cells have pathways that are constitutively turned on and allow for cell growth. I plan on targeting some of these pathways and also study the mechanisms involved with uncontrolled cell growth as well as resistance. This will allow us to improve the survival and quality of life of our patients.