Research Projects Funded by MCCRF

2023 Grants

The Sarah Debord Memorial Grant

Arjun Gupta, M.D. Assistant Professor, Medical Oncology, University of Minnesota. “Characterizing the Time Toxicity of Cancer Care Among People Living with Colorectal Cancer”.

Patients with cancer spend a substantial amount of time on medical care. We conceptualize these time demands as the “time toxicity’’ of cancer care. Patients with colorectal cancer are particularly vulnerable given that chemotherapy is often administered over multiple days, and patients can experience burdensome symptoms and complications. Our research group uses mixed (qualitative and quantitative) methods to investigate time toxicity. We interview patients, care partners, and clinicians to understand their experiences. We analyze objective time burdens faced by patients. This data helps improve cancer care (e.g., bunching appointments to save trips), influences clinical trials (e.g., so trials report the time toxicity of new drugs), and promotes innovation (e.g., home-based care). As a medical oncologist and health services researcher, I use this data to achieve my long-term goal to minimize the time burdens of cancer care, so patients can spend more of their precious time where and how they want.

Norm and Pat Wells Memorial Grant

Matthew Dietz, Graduate Student, University of Minnesota “Quorum Quenching as a Therapeutic Lead for Colorectal Cancer”.

Various gut bacteria are associated with an elevated risk of colorectal cancer (CRC) and a reduced success rate of certain cancer treatments. These bacteria communicate to one another by releasing chemicals in a process called quorum sensing. In fact, some new research has shown that this communication happens between our cells and our gut microbiome as well, encouraging metastasis in colorectal cancer. Our research aims to use enzymes that degrade these communication signals to examine the effects this may have on CRC growth and metastasis in a mouse model. If we can determine what role these communication signals play in cancer development and metastasis, we may be able to use these enzymes as an addition or alternative to existing cancer therapies.

Peter Wilhoit Memorial Grant

Christopher J. LaRocca, M.D. Assistant professor, Surgical Oncology, University of Minnesota and Minneapolis VA Medical Center “Novel Adenovirus-Based Combination Therapies for Colorectal Cancer Treatment”.

Our research group’s main area of investigation is in the use of oncolytic viruses for the treatment of cancer. By modifying an adenovirus (a virus that typically causes common cold symptoms), it can be targeted to selectively infect, replicate within, and kill specific types of cancer cells. In addition, these oncolytic adenoviruses can be designed to express genes at the local tumor site. One such gene is the sodium iodide symporter (NIS), which can be used to facilitate cancer imaging and therapy when combined with radioactive iodine. Our main project is using the NIS-expressing adenovirus to develop a novel treatment regimen for patients with metastatic colorectal cancer.

2022 Grants

norm and pat wells memorial grant

Dechen Wangmo, PHD Student, University of Minnesota “Role of Tumor Cell-Intrinsic Factors in Colorectal Cancer Immune Evasion”

The poor response of most colorectal cancer (CRC) patients to immunotherapy is a major unmet clinical need. Immune evasive mechanisms and lack of a suitable preclinical model that recapitulates human CRC condition underlie the unfavorable response to immunotherapy. To overcome these challenges, I generated mouse tumor organoids modeling Apc-/-, KrasG12D, P53-/-, and Smad4-/- mutations, which are co-mutated with high frequency in advanced CRC. Using CRISPR screening and integrative immune score analysis, I identified CEP55 as a potential target to sensitize the tumor to immunotherapy. Previous studies have shown that CEP55 is overexpressed in other cancers such as breast cancer but its role in CRC is unknown. This research will elucidate how CEP55 promotes tumor progression and immune evasion using tumor organoids.

peter wilhoit memorial Grant

Travis Gates, PHD Student, University of Minnesota “Macrophages as Regulators of Tumor Immunity in Colorectal Cancer” 

Colorectal Cancer (CRC) possesses unique pathological characteristics due to a complex microbiome in the tumor microenvironment (TME) comprised of diverse bacterial species and metabolites, which can alter the activity and function of infiltrating immune cells. Understanding regulatory mechanisms by which the microbiome and its metabolites alter macrophage phenotype and function can lead to novel therapeutic strategies towards increasing tumor-infiltrating T cells, which could expand immune checkpoint inhibitors (ICIs) treatment to more CRC patients. We have found correlations between macrophage subtype and essential amino acid abundances in patient tumor and matched normal tissues from RNA-sequencing, 16S sequencing, and metabolomics. We are currently investigating diagnostic methods to track essential amino acid abundances in stool samples to monitor CRC recurrence. Additionally, we are investigating in vivo tumor models that target essential amino acid transport to see if inhibition of essential amino acid transport can promote immunogenic macrophage subtypes which can synergize with current generation ICIs.

2021 Grants

Dr. Xianda Zhao, University of Minnesota - "The immune regulatory effects of tumor-derived extracellular vesicles in colorectal cancer"

Dr. Elizabeth Adamowicz, University of Minnesota - "Impact of host-microbiome metabolic exchange on colon cancer development"

Glancis Luzeena Raja Arul, Mayo Clinic - “Modeling Adaptive Therapy for Metastatic Colorectal Cancer”

2020 Grants

Dr. Alessia Stornetta, University of Minnesota - "Identification of risk to colorectal cancer using molecular DNA damage profiling from the E. coli-produced genotoxin colibactin in colonoscopy samples"

Dr. Mahendra Pal Singh, Mayo Clinic - "Epigenetic mechanisms of colorectal cancer tumor promotion by Parvimonas micra, an opportunistic pathogenic bacterium of the oral cavity"

Mr. Xianda Zhao, University of Minnesota - "Functions of Atypical Chemokine Receptor 4 (ACKR4) in Anti-tumor Immunity in Colorectal Cancer"

2019 Grants

Dr. Brooke Druliner, Mayo Clinic - "Characterizing telomere and chromatin dynamics in colorectal transformation"

Dr. Seung Ho Shin, The Hormel Institute, University of Minnesota - "Discovery of β-catenin inhibitors for treatment of colon cancer"

2018 Grants

Dr. Rentian Wu, Mayo Clinic - "Targeting the mutant KRAS- or BRAF-induced enhancer as an approach to overcome resistance to 5-fluorouracil−based chemotherapy in colorectal cancer"

Dr. Mizuho Sato-Dahlman, University of Minnesota - "Treatment of metastatic colon cancer by cancer stem cell-targeted oncolytic adenovirus"