Using a heritable immunostimulatory bacterium to block heartworm transmission by mosquitoes

Posted on by PWDF Dev

Summary: Researchers will investigate the use of a bacteria to help block transmission of heartworm parasites by mosquitoes.

Description: More than 150,000 cases of canine heartworm disease are reported annually in the United States alone. Monthly preventive treatments for dogs have been widely available since the mid-19805. However, drug-resistant strains are on the rise, highlighting the need for novel disease control strategies. Researchers will investigate how infection by certain bacteria decreases the capacity of mosquitoes to transmit infectious larvae of Dirofilaria immitis, the agent of heartworm disease. Bacteria-infected mosquitoes (and control groups) will be exposed to both drug-sensitive and drug-resistant parasites. The team hopes findings will provide a new approach to block the spread of the heartworm disease by targeting parasites in their mosquito host.

Co-sponsored with the Morris Animal Foundation, Grant Number: DZ2CA·015

RESEARCHERS

Michael Povelones; University of Pennsylvania
Amount: $10,000

Evaluating Reproductive Diseases in vitro with a 3D Canine Endometrial Organoid Model

Posted on by PWDF Dev

Pyometra is a life-threatening disease that affects over 66% of intact older bitches. Bitches are pre-disposed to this disease due to a number of unique features of their reproductive cycle. Endometritis is an underdiagnosed condition in bitches that results in reduced fertility and can lead to the development of pyometra.

These diseases have mostly been studied in live dogs resulting in welfare concerns and limitations in our understanding of the disease onset and progression and importantly, prevention of these conditions. Organoids are miniature organs in a culture dish that can be grown long-term while maintaining the characteristics and function of the original organ.

This unique 3-dimensional (3D) structure facilitates the study of disease processes such as endometritis and pyometra in canines, potential treatments, and assessment of preventative therapeutics such as novel vaccines. Optimization of canine uterine organoids has the potential to: a) improve the health and welfare of intact middle-aged and older female dogs; b) enhance fertility, genetic gain and health in working dog programs; and c) allow the study of female reproductive diseases without the use of research dogs.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 03055

RESEARCHERS

Fiona Hollinshead, BVSc, PhD; Colorado State University
Amount: $1,000

Artificial Intelligence and Machine Learning for Diagnosis of Dog Sperm Morphology

Posted on by PWDF Dev

Sperm morphology evaluation is an important component of dog fertility analysis. However, visual evaluation of sperm morphology is difficult to teach, and results are largely dependent on the proficiency and experience of the evaluator, leading to large variability in results within and across evaluators.

The objective of this pilot study is to explore recent advances in artificial intelligence for image pattern recognition, similar to that used by the likes of Google and Facebook, to create an automated method for sperm morphology evaluation. A large database with 10,000 dog sperm images will be created. The images will be evaluated by expert veterinarians, then used to train a Convoluted Neural Network (CNN) using deep learning methods. Investigators expect to generate an algorithm capable of classifying sperm morphology with greater than 90% accuracy and precision.

Employing such an algorithm could allow veterinarians to establish more reliable reference values and guidelines for prospective stud dogs and for semen to be used for artificial insemination, improve veterinarian’s abilities to formulate diagnoses and prognoses for infertility problems related to specific sperm defects, and to establish the reproductive safety of drugs and compounds.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 03045-A

RESEARCHERS

Leonardo Brito, DVM, PhD; University of Pennsylvania
Amount: $1,000

Genome-wide Association Study to Investigate Genetic Markers for Antimicrobial Resistance in Mycoplasma cynos Associated with Canine Infectious Respiratory Disease

Posted on by PWDF Dev

Mycoplasma cynos is an emerging respiratory bacterium in dogs. It is associated with kennel cough and may lead to fatal pneumonia. This bacterium is very complex, and the lack of standardized diagnostic and knowledge on antibiotic therapy makes clinical management difficult. Since no vaccine is available, current treatment of M. cynos-associated outbreaks relies on antibiotics. However, the in vitro activity of antibiotics against M. cynos has never been studied and the effectiveness of antibiotic therapy for M. cynos disease is completely unknown. This may lead to unsuccessful treatment and antibiotic resistance.

In vitro testing of antibiotics is an urgent need to provide appropriate treatment, and to avoid inappropriate use of antibiotics. Unfortunately, these tests are very time-consuming for mycoplasmas, partially explaining the absence of information on M. cynos.

In this project, researchers will investigate the in vitro activity of antimicrobials against M. cynos isolated from dogs with respiratory disease, and implement the first genome-wide association study to identify genetic mutations linked to antibiotic resistance in M. cynos, which has never been investigated before. This will help develop genetic-based diagnostic assays for the rapid detection of resistant Mycoplasma isolates to better allow the results to inform clinical therapy. Results from this project will direct effective diagnosis and therapeutic interventions for an emerging respiratory disease in dogs.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 03053-A

RESEARCHERS

Grazieli Maboni, DVM, MSc, PhD; University of Guelph
Amount: $1,000

Understanding the Genetic Basis of Addison’s Disease in PWDs

Posted on by PWDF Admin

Addison’s disease is a common, life-threatening disorder in dogs characterized by the immune-mediated destruction of portions of the adrenal gland. This damage prevents the adrenal gland from synthesizing hormones that are necessary for normal cell metabolism, kidney function, and maintenance of the immune system. Dogs with Addison’s disease are also highly predisposed to succumbing to a life-threatening adrenal crisis. Addison’s disease is most common in Portuguese Water Dogs (PWDs), which have a 29-fold greater risk of developing the disease compared to other dog breeds, indicating a strong genetic component. To date, no genetic variants have been associated with Addison’s disease in PWDs.

This lack of knowledge has prevented the development of a genetic test that would allow for prediction of a dog’s disease risk and the development of informed breeding practices related to Addison’s disease. In this study, we will use state-of-the-art scientific tools to understand the genetic basis of Addison’s disease in PWDs. The data generated here will provide the foundation for the development of a genetic test for Addison’s disease in PWDs, enabling early diagnosis and treatment, as well as maintenance of genetic diversity within the breed while helping to decrease disease incidence.

Research funded by the Portuguese Water Dog Foundation, Inc.

For additional details including eligibility criteria and how to enroll, please visit Dr. Friedenberg’s page for the Addison’s Disease – Genetics Study in Portuguese Water Dogs Study.

Related News

Announcement: Understanding the Genetics of Addison’s Disease in PWDs
FAQs Addison’s Disease Research in PWDs

Webinar

Dr. Friedenberg’s on March 28, 2023 on Addison’s disease and his investigation into the genetic component of the disease. This research made possible through your generous support of the Portuguese Water Dog Foundation.

RESEARCHERS

Steven Friedenberg, DVM, PhD, University of Minnesota
Leigh Anne Clark, PhD, Clemson University
Amount: $226,000
Administrative Amount: $2,300

Luteinizing Hormone Receptor Activation Induces Migration and Adhesion in Neoplastic Canine Lymphocytes

Posted on by Janet Boyd

Luteinizing hormone (LH) is secreted from the brain (pituitary) in sexually intact dogs to stimulate synthesis of estrogen and testosterone in females and males, respectively. However, LH is secreted at concentrations up to 20 times higher following gonad removal with spaying or castration because hormonal negative feedback is lost. Although LH is considered to be a reproductive hormone, there are dozens of non-reproductive tissues in dogs that contain receptors for LH including immune system cells, specifically lymphocytes.

Lymphoma is a common malignant cancer of dogs involving lymphocytes, and spayed/castrated dogs are reportedly 3-4 times more likely to develop lymphoma. Conventional chemotherapy results in remission in approximately 60-90% of cases with a median survival time of 6-12 months. Preliminary work has identified LH receptors in canine lymphoma tissue and demonstrated LH- receptor-induced proliferation of neoplastic lymphocytes in vitro.

This study aims to determine if LH receptor activation induces adhesion and migration of neoplastic lymphocytes in vitro. Characterizing the role of LH receptor in neoplastic lymphocyte proliferation may help guide future lymphoma treatment options.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02751-A

RESEARCHERS

Michelle Kutzler, DVM, PhD; Oregon State University
Amount: $3,000

Identifying Early Stage Ultra-rare Mutations as Predictive Biomarkers of Lymphoma in High-risk versus Low-risk Breeds Within the Dog Aging Project

Posted on by Janet Boyd

The most common type of cancer in dogs is lymphoma, with ~80,000 cases diagnosed annually in the United States. Breeds vary in their risk of lymphoma, but it is unclear why there is variation despite considerable effort to identify the genetics of cancer risk and progression in dogs. Cancer typically arises from the accumulation of non-inherited (i.e. somatic) mutations. However, variation among breeds in cancer risk could be due to breed-specific variation in the types of mutations, the rate of accumulation of mutations, or the downstream effects of mutations in healthy dogs.

This study will use novel sequencing technology to test the hypothesis that breed-specific lymphoma risk is due to variation in the frequency and type of rare precancerous mutations. Normally, measuring these low-frequency mutations has been beyond the range of standard sequencing technology, which is limited to detecting mutations present in >1% of cells. The new technology applied here represents a >10,000-fold improvement in accuracy, enabling the investigators to accurately detect a precancerous mutation present at a single site at a frequency of just one out of every 10 million DNA base pairs. By determining if mutation frequency in blood of healthy high-risk and low-risk dogs can predict lymphoma risk, this work could lead to the development of novel tests for the early diagnosis and prognosis of canine lymphoma.

This work has the potential to shed light on the mechanisms that underlie breed-specific variation in lymphoma risk, and in the long term, could lead to the development of novel tests for the early diagnosis and prognosis of canine lymphoma.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 2772

RESEARCHERS

Daniel Promislow, PhD; University of Washington
Amount: $10,000

Reprogramming the Tumor Immune Niche in Canine Hemangiosarcoma

Posted on by Janet Boyd

Hemangiosarcoma (HSA) is a common, devastating disease of dogs. The malignant tumor is seen frequently in older Golden Retrievers, German Shepherd Dogs, Portuguese Water Dogs, Labrador Retrievers, and Schnauzers, but it can occur in any dog of any breed at any age. Survival times of dogs with the tumor are short, even with surgical removal and standard of care treatment. Inflammation within the tumor tissue is common in canine HSA, and the immune response may contribute to tumor heterogeneity and prognosis for the dog. Yet, the immunological features in the context of the HSA niche are virtually unknown. The investigators have found that HSA cells have a strong capacity to promote proliferation and differentiation of hematopoietic stem and progenitor cells, with increased inflammatory cytokines, suggesting a niche regulatory function of HSA cells.

This study will focus on understanding the functional relationships between HSA cells and immune cells that contribute to the tumor niche to identify molecular mechanisms that regulate critical signaling pathways in canine HSA. This approach will improve our understanding of the tumor immunity and heterogeneity, as well as aid in patient selection for novel immunotherapies.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 2759

RESEARCHERS

Jong Hyuk Kim, DVM, PhD; University of Minnesota
Amount: $5,000

Optical Coherence Tomography for Margin Evaluation of Canine Skin and Subcutaneous Neoplasms

Posted on by Janet Boyd

Skin cancer is common in older dogs and often requires surgery to treat. For these tumors, the best chance of cure is offered if the surgeon can fully remove both visible and microscopic traces of the tumor. Currently surgeons must rely on pathologist’s assessment of tissues after surgery and the success of the procedure will not be known until several days later. This result is important as residual cancer may need further surgery or other treatments like radiation therapy. Additional treatments such as these can result in further risk and discomfort for dogs as well as be an emotional and financial cost for owners. Optical coherence tomography is an emerging diagnostic imaging tool that uses light waves to generate real-time, high-resolution images of tissue at a microscopic level. These images can be used to evaluate for residual disease at the time of surgery giving immediate feedback to the surgeon.

This study will focus on validating this technology for the imaging of surgical margins of canine skin and subcutaneous tumors. If successful, this technology could be used to assess for residual cancer intra-operatively to benefit patients by guiding accurate treatment recommendations.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 2758

RESEARCHERS

Laura Selmic, BVetMed, MPH; Ohio State University Research Foundation
Amount: $5,000

Bladder Carcinogen Exposures in Pet Dogs

Posted on by Janet Boyd

Bladder cancer is an aggressive cancer that affects ~ 20,000 dogs per year, and often leads to euthanasia. Certain breeds have a higher incidence of bladder cancer but genetic studies even in the highest risk breeds have been inconclusive and still indicate influence from environmental exposures. The investigators propose that specific household environmental chemical exposures contribute to the risk of bladder cancer in dogs.

In this study, they will measure urinary concentrations of five different chemicals that are known or suspected to be bladder carcinogens, in dogs with bladder cancer compared to unaffected dogs. The investigators will determine whether the presence of certain chemicals is associated with household exposures, based on owner questionnaires and household proximity to industrial sites. Finally, they will determine whether urinary chemical concentrations are linked to early DNA damage in the urinary cells of healthy dogs that do not have bladder cancer. The overall goal of this study is to provide veterinarians and dog owners with evidence-based bladder cancer prevention strategies.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 2780

RESEARCHERS

Lauren Trepanier, DVM, PhD; University of Wisconsin, Madison
Amount: $15,000