American Cancer Society Institutional Research Grant Awardees

2022 Awardees

Dr. Caitlin Allen

Caitlin Allen, Ph.D., MPH

Assistant Professor, Department of Public Health Sciences

“KEEP IT (Keeping Each Other Engaged via IT): An Innovative Digital Literacy Training Program for Community Health Workers about Hereditary Breast and Ovarian Cancer among Black Women”

The goal of this project is to develop and launch a new training program for community health workers called KEEP IT (Keeping Each other Engaged Program via IT). KEEP IT is an innovative training for community health workers designed to build their competencies in using health IT tools to facilitate identification, screening, and access to genetic services among African American women who are at increased risk for hereditary breast and ovarian cancer.

Although recent studies have found higher prevalence of genetic mutations associated with hereditary breast and ovarian cancers among African American women, less than half of eligible African American women are assessed for genetic risk and only 28% engage in risk-reducing interventions. Community health workers are trusted members of communities with established relationships with individuals and families, so we hope that by empowering them with the right education, tools, and resources they can in-turn work with their clients to overcome common barriers. Our hope is that this training program helps move us closer to addressing cancer inequities and contributes toward growing efforts in reducing disparities in access to precision medicine.

 

Leonardo Ferreira, Ph.D.

Leonardo Ferreira, Ph.D.

Assistant Professor, Department of Microbiology and Immunology

“Repurposing Regulatory T-Cells for Cancer Control Using Chimeric Antigen Receptors”

Redirecting T-cells to directly recognize proteins on the surface of cancer cells using chimeric antigen receptors (CARs) has dramatically improved the remission rate of previously incurable cancers. A CAR is a man-made molecule that combines an antibody-derived fragment to recognize a desired cancer molecule and an array of T-cell signaling domains that instruct the CAR T-cell to kill cancer cells with the target molecule. The FDA has now approved five CAR T-cell therapies targeting CD19, a molecule expressed in B-cell-derived leukemia.

However, while success stories of CAR T-cell therapy curing liquid cancers abound, the same is not true of solid tumors. The solid tumor microenvironment has proven hard to penetrate to anticancer T-cells. And even to those T-cells that do manage to penetrate, the tumor microenvironment is inhospitable with its lack of oxygen and glucose, excess of lactic acid, and the presence of immune suppressive molecules and cells. One type of such immune suppressive cells are regulatory T-cells (Tregs). Tregs are a subset of T-cells dedicated to inhibiting immune responses, essential to preventing autoimmunity and tissue damage.

Yet, in the context of solid tumors, infiltrating Tregs signify a poor prognosis. What if we could repurpose these tumor Tregs and turn them against cancer cells? Tregs interact almost exclusively with professional antigen presenting cells, such as macrophages and dendritic cells, and have been reported to kill them in some instances as one of their many suppression mechanisms. I have redirected Tregs with an anti-CD19 CAR and found that they kill CD19-positive tumor cells in the Petri dish. This institutional American Cancer Society award will allow me to test whether CAR Tregs can successfully infiltrate and destroy solid tumors and dissect the mechanisms behind their killing activity, potentially leading to new strategies to eliminate solid tumors.

 

Dr. Gary Gao

Xueliang Gao, Ph.D.

Assistant Professor, Department of Cell and Molecular Pharmacology and Experimental Therapeutics

“Targeting EMT for PTEN Null Castration-resistant Prostate Cancer (CRPC) Bone Metastasis”

The development of prostate cancer heavily depends on the availability of circulating androgen. Androgen deprivation coupled with surgery is often an effective therapeutic method for prostate cancer patients. A common outcome of androgen deprivation in prostate cancer therapy is disease relapse and progression to castration-resistant prostate cancer (CRPC) via multiple mechanisms. Bone metastases develop in approximately 30% of patients with CRPC within two years of castrate resistance.

Mechanistic studies of CRPC bone metastases are key for facilitating the discovery of more effective treatments. PTEN deletions are found in 20-40% of localized prostate tumors and up to 60% of metastases. The purpose of my study is to elucidate the molecular mechanisms involved in CRPC bone metastases of PTEN null tumors. The long-term objective of my study is to understand the mechanisms that govern CRPC progression, and to devise new treatments for CRPC.

 

Dr. Jessica Hartman

Jessica Hartman, Ph.D.

Assistant Professor, Department of Biochemistry & Molecular Biology

“Conserved Role of Tetraploidy in Mammalian Hepatocytes and C. elegans”

Fatty liver disease impacts a third of U.S. adults and can progress to liver cancer. This progression from healthy liver to fatty liver to cancer involves dramatic changes in the number of copies of the genome (DNA) per cell. The cues that guide increases and decreases in that DNA content (ploidy) are largely unknown.

In the first year of the award, our group successfully cultivated and characterized Caenorhabditis elegans (microscopic roundworms) with either two (normal, diploid) or four (tetraploid) genomes in every cell in their bodies. We found that the differences between these two states closely resembled what has been previously reported in the liver.

In this renewal application, we propose to follow up on this finding to use our worm model along with a three-dimensional liver cell culture model to better understand what is controlling the DNA content in healthy liver, diseased liver, and liver cancer. Altogether, our study will take advantage of the very powerful genetic model C. elegans to better understand the conserved biology of polyploidy and its role in cancer. 

 

Dr. Natalie Saini

Natalie Saini, Ph.D.

Assistant Professor, Department of Biochemistry and Molecular Biology

“Understanding the Role of Persistent Inflammation in Driving Carcinogenesis”

Autoimmune diseases with persistent inflammation have been associated with increased cancer incidence. Systemic sclerosis is one such autoimmune disease with elevated risk for lung cancer. However, the process by which inflammation drives carcinogenesis is not known. Here, we aim to understand how persistent inflammation leads to DNA damage in pre-cancer cells and whether uncorrected DNA damage leads to mutations in cancer-driver genes.

Our work will provide a link between inflammation-induced genome changes and cancer in patients with systemic sclerosis. The proposal outcomes will fill a critical knowledge gap of a fundamental question in cancer biology by addressing the role of inflammation-driven genome-instability in driving carcinogenesis. Such information is important to develop earlier diagnostics and better therapeutic interventions for immune-mediated lung cancers.

 

Dr. Tracy Smith

Tracy Smith, Ph.D.

Assistant Professor, Department of Psychiatry and Behavioral Sciences

“E-cigarettes as Harm Reduction Tools in Smokers who Fail to Quit with Traditional Methods”

The goal of the proposed study is to understand whether current smokers who have failed to quit smoking with traditional methods would benefit from trying to switch completely to a less harmful product, like e-cigarettes. Smokers who have previously failed to quit will be assigned to either 1) try to quit again with nicotine replacement therapy or 2) try to switch completely to an e-cigarette. Everyone will receive 5 weeks of medication or e-cigarettes, and everyone will choose a day to completely stop smoking within one week of receiving their medication or product.

During the study, we will collect information from the participants about their smoking and use of their assigned product, as well as a breath sample that measures whether the participants have recently smoked. The proposed trial will be one of the first trials in the United States to directly compare e-cigarettes for complete switching to FDA-approved pharmacotherapy for smoking cessation.

 

2021 Awardees

Thomas Curran, M.D.

Thomas Curran, M.D., MPH

Assistant Professor, Department of Surgery

“Anti-neoplastic Effect of Low Molecular Weight Heparin after Major Gastrointestinal Oncology Surgery and Disparities in the Utilization of Extended Venous Thromboembolism Prophylaxis”

We aim to study the anti-cancer effect of low dose blood thinners after major gastrointestinal cancer surgery and disparities in the use of these blood thinners. Patients undergoing surgery for gastrointestinal cancers are at increased risk of blood clots (deep vein thrombosis and pulmonary emboli) which may cause serious health consequences. As a result, cancer organizations such as the National Comprehensive Cancer Network recommend consideration of preventative dose blood thinners for 30 days after major cancer surgery.

While these medications have been shown to decrease the occurrence of blood clots in clinical trials, basic laboratory research suggests that certain blood thinners such as enoxaparin may also have an anti-cancer effect with potential impact on cancer-related survival. However, our understanding of the association between enoxaparin use and cancer-related survival in humans is limited. Our team will use a national cancer registry to evaluate whether patients receiving enoxaparin have improved cancer-related survival. We will also evaluate the association of social determinants of health such as race and geography on the usage of enoxaparin. This study has the potential to improve the care of our cancer patients and mitigate disparities in the delivery of cancer care.

 

Dr. Carsten Krieg

Carsten Krieg, Ph.D.

Assistant Professor, Department of Microbiology & Immunology

“A Lipid Metabolic Switch to Enhance Immunotherapy of Cancer”

Monocytes are members of our inherited immune system and significant initiators of anti-tumor immune responses. As such, they are reported to support tumor growth by suppressing the adaptive immune system. When omitted, they are potent initiators of anti-tumor immunity. Thus studying the impact of monocytes on cancer immunity is of great value. We tracked individual immune cells during anti-tumor immunotherapy in patients. We observed that increased circulating monocytes correlate with response. A deeper investigation of monocytes in patients responding to therapy revealed an enhanced fat metabolism. The focus of this ACS-IRG pilot study is how altered fat metabolism in monocytes affects their function in inducing anti-tumor immunity.

 

Dr. Jessica Hartman

Jessica Hartman, Ph.D.

Assistant Professor, Department of Biochemistry & Molecular Biology

“The Effects of Tetraploidy on Sphingolipid Metabolism and Chemosensitivity in C. elegans”

Cancer treatments such as chemotherapy and radiation are effective for destroying most cells within a tumor, but in many cases, a small number of resistant cells remain. Those resistant cells have unique properties: they are initially non-dividing, stress-resistant, giant cells that have extra copies of their genomes (called polyploidy).

When they eventually do divide, the recurring cancer is often more aggressive than the initial tumor. To better understand how those stress-resistant cells work, we are using roundworms called Caenorhabditis elegans that, when stressed, form larger animals that are stress-resistant and also carry extra copies of their genomes. Using innovative tools available to study these worms, we hope to find new ways to identify and target resistant polyploid cancer cells and improve cancer treatments.

 

Dr. Aaron Hobbs

Aaron Hobbs, Ph.D.

Assistant Professor, Department of Cell & Molecular Pharmacology and Experimental Therapeutics

“Defining the Role of Overexpressed PI3K Isoforms in Compensating for the Atypical KRASG12R Mutation in Pancreas Cancer”

Pancreatic cancer will become the 2nd most deadly cancer in the U.S. by 2030. Pancreatic cancer is defined by the presence of a KRAS mutation, which is mutated in 95% of pancreatic cancer patients. Of these, nearly 20% have the KRASG12R mutation. KRASG12R uniquely fails to regulate several metabolic programs previously assigned to mutant KRAS function. I have shown that KRASG12R cannot activate PI3Kα. Further, I showed that multiple PI3K isoforms are overexpressed in pancreas cancer.

This proposal seeks to define the role of the many PI3K isoforms in the pancreas. In addition, I have observed that KRASG12R cell lines are sensitive to the loss of the RALA and RALB small GTPases. RAL GTPases have been understudied in pancreatic cancer. Therefore, RAL signaling, in the context of KRASG12R, will be determined. This proposal uses KRASG12R to define the role of KRAS in the promoting of pancreas cancer. My research has shown that all KRAS mutations are not created equal. This proposal seeks to expand on that observation by defining KRASG12R-specific signaling. Data from these studies will be used to develop new targeted therapies for pancreatic cancer. 

 

Haizhen (Jen) Wang

Haizhen (Jen) Wang, Ph.D.

Assistant Professor, Department of Cell & Molecular Pharmacology and Experimental Therapeutics

“CDK6 in T Cell Leukemia Infiltration”

An enzyme known as phosphofructokinase, platelet (or PFKP), which plays an important role in breaking down glucose to create energy, is important in clinical cancer research because its cellular expression level is associated with decreased survival rates in cancer patients. Preliminary data and analyses from Dr. Wang’s lab suggest that PFKP moves into the nucleus, which is the part of a cancer cell that contains its genes and controls its growth and production, to regulate leukemia, allowing it to spread throughout multiple organs and preventing the body’s immune system from recognizing and killing the cancer cells.

In this study, Dr. Wang’s lab will test how preventing the movement of PFKP into the nucleus affects the treatment of leukemia outside of humans. The study will also look at whether PFKP that is found in the nucleus can help predict whether a patient may develop an aggressive form of T cell leukemia.

 

2020 Awardees

Jezabel Rodriguez-Blanco

Jezabel Rodriguez-Blanco, Ph.D.

Assistant Professor, Department of Pediatrics

"Identification of Novel Regulators of Tumor Propogation in SHH Subgroup Medulloblastoma"

Silvia Guglietta

Silvia Guglietta, Ph.D.

Assistant Professor, Department of Microbiology & Immunology

"Gut Vascular Barrier Disruption as a New Biomarker for Hematogenous Dissemination of Colorectal Cancer Liver Metastases"

Subramanya Pandruvada, Ph.D.

Subramanya Pandruvada, Ph.D.

Assistant Professor, Department of Oral Health Sciences

"Targeting SHP2-dependent Tumor Immune Cell Infiltration in Head and Neck Cancer"

Haizhen (Jen) Wang

Haizhen (Jen) Wang, Ph.D.

Assistant Professor, Department of Cell & Molecular Pharmacology and Experimental Therapeutics

“CDK6 in T Cell Leukemia Infiltration”

Jie Zhang

Jie Zhang, Ph.D.

Assistant Professor, Department of Cell & Molecular Pharmacology and Experimental Therapeutics

"Role of Microsomal Glutathione Transferase 1 in Melanoma Melanogenesis and Metastasis"

2019 Awardees

Peggi Angel, Ph.D.

Peggi Angel, Ph.D.

Assistant Professor, Department of Pharmacology

"2D Typing of Collagen Stroma as a Novel Tissue Marker for ER-Negative/ER-Positive Breast Cancer"

Jennifer Dahne, Ph.D.

Jennifer Dahne, Ph.D.

Assistant Professor, Department of Psychiatry & Behavioral Sciences

"Development and Evaluation of a Low-Cost, Remote Method to Biochemically Verify Smoking Status"

Barry Gibney, DO

Barry Gibney, D.O.

Assistant Professor, Department of Surgery

"Non-small Cell Lung Cancer: The Role of the MHC Class I in Gender-Specific Survival"

Breege Howley, Ph.D.

Breege Howley, Ph.D.

Research Assistant Professor, Department of Biochemistry & Molecular Biology

"Characterizing the Role of Interleukin-like EMT Inducer (ILEI) in Breast Cancer Recurrence"

Wei Jiang

Wei Jiang, M.D.

Associate Professor, Department of Microbiology & Immunology

"The Role of Microbiome in Prostate Cancer Progression"

Jorge Munera

Jorge Munera, Ph.D.

Assistant Professor, Department of Regenerative Medicine & Cell Biology

"An In Vitro Model of Juvenile Polyposis Syndrome Using Human Pluripotent Stem Cell Derived Colonic Organoids"

Subramanya Pandruvada, Ph.D.

Subramanya Pandruvada, Ph.D.

Assistant Professor, Department of Oral Health Sciences

"Targeting SHP2-dependent Tumor-immune Cell Infiltration in Head and Neck Cancer"