Pathology Residency Training Program to support the Morris Animal Foundation Golden Retriever Lifetime Study

This grant supports the advanced training of two aspiring veterinary pathologists who will assist with the analysis of tissue samples collected from dogs enrolled in Morris Animal Foundation’s Golden Retriever Lifetime Study.

Highly trained investigators are vital to advancing the health and welfare of animals. Morris Animal Foundation is funding the training of two new veterinary pathologists to work with the Golden Retriever Lifetime Study research team. Under the mentorship of the study’s veterinary leadership team, the selected pathology residents will help examine submitted tissue samples from study participants in order to provide consistency in diagnosis of diseases, including cancer, as well as assist with advanced pathology diagnostics and reporting as needed.

Co-sponsored with the Morris Animal Foundation, Grant Number: D16CA-001

RESEARCHERS

EJ Ehrhart, DVM, PhD, DACVP, Colorado State University
Amount: $10,000

Understanding the Relationship between Intestinal Bacteria and Inflammatory Bowel Disease (IBD)

Scientific Title: Tackling the Canine Microbiome in Chronic Enteropathy: Characterizing the Functionally Significant Changes that Occur with Remission of Disease

Summary: Researchers are looking at changes in gut bacteria that stimulate the immune system in dogs with inflammatory bowel disease to help identify novel ways to diagnose and treat this disease.

Description: Inflammatory bowel disease (IBD) is a common disease of dogs, causing vomiting, diarrhea and weight loss. Some studies suggest that specific intestinal microbiota can drive or exacerbate intestinal inflammation, but this mechanism has not been well studied in dogs. Researchers will assess and track certain bacteria, known to interact directly with the gut immune system, in stool samples of dogs with inflammatory bowel disease. Data will be collected during treatment until the dogs gain remission. Findings will validate if these bacteria are functionally important to the disease process, and how treatment modifies the gut bacteria.

This new information will lead to a better understanding of how the gut microbiome can be manipulated in dogs with IBD and may reduce the need to directly biopsy the intestine to establish a definitive diagnosis of this condition.

Co-sponsored with the Morris Animal Foundation, Grant Number: D18CA-045

RESEARCHERS

Dr. Caroline S Mansfield
The University of Melbourne, Australia
Amount: $10,000

Investigating Cancers and Exposure to Environmental Chemicals

Scientific Title: Detoxification of Environmental Carcinogens by Glutathione-Stransferases in Dogs

Summary: Researchers will find out how the dog’s body breaks down common environmental chemicals that have been linked to cancers in humans.

Description: When dogs or humans are exposed to toxic chemicals in the environment, they use glutathione-S-transferase (GST) enzymes to break down and neutralize those chemicals. When GST enzymes are not working, toxic chemicals sometimes lead to cancers such as lymphoma or bladder cancer. Researchers will test how well four major GST dog enzymes can neutralize several common environmental chemicals, including those found in tobacco smoke and yard products.

Results will provide a clearer understanding of whether individual dogs with low-acting GSTs may be sensitive to specific chemicals and, as a result, more susceptible to developing environmentally associated cancers.

Co-sponsored with the Morris Animal Foundation, Grant Number: D18CA-070

RESEARCHERS

Dr. Lauren A Trepanier
University of Wisconsin-Madison
Amount: $10,000

Measuring Chemotherapy Drug Resistance in Dogs with T-cell Lymphoma

Quantitative Assessment of Minimal Residual Disease Kinetics during CHOP Chemotherapy of Canine T-cell Lymphoma via Next-Generation TCRVß Sequencing

Human cancer treatment is becoming more and more tailored to each individual case and tumor characteristics. This study will be conducted by researchers at North Carolina State University and will follow a small number of cells that evade chemotherapy agents, providing information on the effectiveness of particular agents against T-cell lymphoma. The data from this study will be used to personalize treatment protocols for dogs on an individual basis in hopes of improving outcomes, survival rates, and quality of life.

Description: Since the use of combination chemotherapy was first reported in 1968, little progress has been made in improving the survival of dogs with T-cell lymphoma. Effectively monitoring chemosensitivity – the number of tumor cells killed by chemotherapy– of individual lymphoma cells exposed to multiple agents over many treatments remains a challenge. Following the small numbers of cells that evade chemotherapy would provide information on the effectiveness of a particular chemotherapy agent.

In this clinical trial, researchers will use state-of-the-art DNA technology to measure changes in this small population of resistant cancerous T-cells in client-owned dogs with lymphoma. Data will be used to personalize treatment protocols for individual dogs in hope of improving survival and quality of life.

Co-sponsored with the Morris Animal Foundation, Grant Number: D16CA-056

RESEARCHERS

Dr. Paul R. Hess, DVM, PhD
North Carolina State University
Amount: $10,000

Developing a New Tool to Study Viral Infections and Cancer in Dogs

Development of an MHC Class I Tetramer to Study Virus- and Tumor-specific CD8+ T-cell Responses in Dogs

Summary: Researchers will develop a state-of-the-art molecular tool to track and study killer T-cell populations that are responsible for fighting viral infections and cancer in dogs.

Description: In humans, a powerful immunologic reagent called a tetramer is standardly used to visualize changes in the body’s killer T-cells. These cells respond to immunologic challenges and are critical to the body’s immune system.

Current knowledge of T-cell behavior in dogs could be significantly advanced with the development of a dog-specific tetramer. Researchers will work to construct the first canine tetramer, which would then be used in the development of vaccines for infectious diseases and cancer in dogs.

Co-sponsored with the Morris Animal Foundation, Grant Number: D15CA-015

RESEARCHERS

Dr. Paul R. Hess
North Carolina State University

Exploring New Medical Treatments for Cushing’s Syndrome in Dogs

Novel Medical Approach to Canine Hyperadrenocorticism with Melanocortin 2 Receptor (MC2R) Antagonist and Steroidogenic Factor 1 (SF-1) Inverse Agonists

Summary: Researchers will investigate potential new medical treatments for canine Cushing’s syndrome.

Description: Cushing’s syndrome is a hormonal disorder that occurs when the body produces higher than normal levels of the hormone cortisol. Unhealthy levels of cortisol can be triggered by various causes, including pituitary and adrenal gland tumors.

Researchers will assess how two novel compounds affect cortisol production and adrenal tumor growth. Identifying novel medical options will help improve treatment strategies for dogs with Cushing’s syndrome.

Co-sponsored with the Morris Animal Foundation, Grant Number: D15CA-052

<h5>RESEARCHERS</h5>
Dr. Sara Galac
Utrecht University, The Netherlands

Testing a Potential Therapeutic Target for Lymphoma

Valosin-Containing Protein (VCP): A Novel Therapeutic Target for Canine Lymphoma

Summary: This study investigates a new therapeutic target (valosin-containing protein) for dogs with lymphoma.

Description: A cure for canine lymphoma remains elusive, in part because of the lack of molecular-targeted therapies that can circumvent chemotherapy resistance. The research team’s previous findings suggest that valosin-containing protein (VCP) holds particular promise as a therapeutic target.

In this study, they will test a known inhibitor of VCP to see if this results in preferential killing of lymphoma cells over healthy cells and to determine the critical mechanisms through which the anticancer effect is achieved. Identifying new therapeutic targets for canine lymphoma is the first step toward developing better treatments for this deadly disease.

Co-sponsored with the Morris Animal Foundation, Grant Number: D14CA-324

RESEARCHERS

Dr. Marie-Eve Nadeau
University of Montreal, Canada

Testing Strategies to Treat Drug-Resistant Hemangiosarcomas

Lysosomal Drug Sequestration by CSF-1R (High) Tumor Cells Contributes to Drug Resistance in Canine Hemangiosarcoma

Summary: Investigators are assessing the potential for a specific tumor-cell population in canine hemangiosarcoma to sequester drugs within their lysosomes as a novel mechanism of drug resistance.

Description: Canine hemangiosarcoma is a common and highly metastatic cancer that affects all breeds of dogs. These tumors are particularly drug resistant, which makes them difficult to treat.

The investigators recently identified a more drug-resistant cell population in hemangiosarcoma. These cells appear to be extremely efficient in isolating cancer drugs and preventing them from reaching their targets. The investigators will use several strategies to try to disrupt this process and they will determine whether any of these approaches improves drug responses and diminishes drug resistance. This could lead to more effective treatment of this difficult cancer.

Co-sponsored with the Morris Animal Foundation, Grant Number: D14CA-047

RESEARCHERS

Dr. Erin B. Dickerson
University of Minnesota

Exploring the use of a Virus Based Anticancer Strategy for Lymphoma

A Clinical Trial of VSV-cIFNbeta-NIS Oncolytic Virotherapy for Canine B-Cell Lymphoma

Summary: This study explores the safety and effectiveness of a new virus-based therapy, developed at Mayo Clinic, for dogs with B-cell lymphoma.

Description: Lymphoma is one of the most commonly occurring malignant tumors in dogs. Though treatable, the disease often recurs and spreads. This study will determine the safety, efficacy and prognostic factors of a cancer-killing virus developed by researchers at the Mayo Clinic. Researchers at the University of Tennessee have already determined a safe dosing protocol for this virus in healthy dogs, and this clinical trial will test the dosing in dogs with B-cell lymphoma.

Using state-of-the-art cancer imaging, the study team will determine how successfully the virus spreads to sites of cancer. They will also study the dogs’ immune responses to the virus. This study provides the first robust assessment of a new anticancer strategy that has the potential to significantly improve quality of life and outcomes for dogs suffering from lymphoma.

Co-sponsored with the Morris Animal Foundation, Grant Number: D14CA-002

RESEARCHERS

Dr. Amy K. LeBlanc
University of Tennessee

Developing Ways to Improve Cancer Treatments

Methods of predicting tumor response to a given chemotherapy protocol have historically focused on a few traits that could be measured in biopsy samples. Recent approaches have looked at the activity of genes within tumors to predict a tumor’s sensitivity to a given drug. Because many dogs with osteosarcoma eventually succumb to it in spite of treatment, a method to optimize chemotherapy selection could improve outcomes for dogs with this type of cancer.

Funded by Morris Animal Foundation, researchers from Colorado State University are developing a model to determine whether an osteosarcoma tumor from an individual dog is sensitive to a specific chemotherapy drug. This project is based on the idea that the genetics of human and canine cancers are similar enough that the wealth of data on human cancer genes and drug sensitivity can be mined and applied to canine cancers to aid in chemotherapy selection for dogs.

So far, researchers have collected genetic and drug-sensitivity data from canine cancer cell lines to compare with human data used to evaluate an individual tumor’s likely response to specific chemotherapy drugs. Currently, the researchers are looking at several commonly used drugs—doxorubicin, carboplatin and cisplatin—to determine if the human models will be accurate in predicting canine cancer responses to these drugs. Results are promising, and the next step is to use the gene expression–based models to search drug databases for drugs that could be more effective in treating canine osteosarcoma patients than the drugs that are the current standard of care.

If the study is successful, canine patients could be treated with the drug that would be most effective for their particular cancer. Data from this study could also lead to new treatment options for osteosarcoma. This type of approach, known as precision medicine, allows for tailored therapy that better controls cancer growth and spread and minimizes the possibility of using an ineffective drug that may cause unwanted side effects.

Co-sponsored with the Morris Animal Foundation, Grant Number: D13CA-044

RESEARCHERS

Daniel L. Gustafson, PhD
Colorado State University