Multi-Modal Strategies for Discriminating IBD from Alimentary Lymphoma in Cats

Inflammatory Bowel Disease (IBD) and small cell lymphoma (SCL) are two common causes of chronic gastrointestinal (GI) disease in cats, each with different treatment options and prognoses.

IBD is believed to result, at least in part, from inflammatory reactions by the GI tract’s immune system to various allergens (i.e. food, bacteria), although genetic predisposition and other factors may play a role. The cause of SCL is also likely multifactorial, and some evidence supports the notion that chronic IBD can progress to SCL in cats.

Distinguishing feline IBD from SCL is challenging, and currently requires microscopic evaluation of biopsy samples obtained by either surgery through an abdominal incision or by endoscopy, which involves passing a flexible camera into the GI tract through either the mouth or the rectum.

Even when such biopsies are obtained, though, their interpretation by pathologists is subjective, and is influenced by the fact that the sites from which biopsies are obtained may not be representative of the status of the GI tract as a whole. These factors make decision-making in the management of affected cats challenging in many cases.

This unique study aims to use artificial intelligence to develop automated, computational methods to evaluate biopsy specimens from cats with chronic GI disease, with the goal of improving our ability to distinguish between IBD and SCL in cats.

A secondary goal of this study is to follow cats diagnosed with IBD over time (with abdominal ultrasound and GI biopsies) to determine whether a diagnosis of IBD increases the risk of a cat ultimately developing SCL.

Finally, this study will preliminarily evaluate the feasibility of using a technique called elastography, which quantifies the elasticity (stretchiness) of the intestines using non-invasive abdominal ultrasound, to distinguish between IBD and SCL in cats.

Investigator: Parminder Basran, PhD

Feline FAANG: What Makes a Cat a Cat?

The complete set of genetic material (DNA) within an organism is referred to as its genome, and while knowledge of the genome of a species is certainly crucial to understanding how it functions in both health and disease, this is not the full story.

Understanding how the genome is expressed (i.e. which pieces of DNA are translated, in which tissues/organs, at what stage of life, and under which conditions) and what each particular region of DNA does (called annotation) is often just as important as knowing the DNA sequence itself, as it has become clear that not all of a species’ DNA is expressed at all times and in all tissues. In fact, it is the combination of the genome and the control of how and when it is expressed across different organs/tissues that truly makes each species and each genetically-mediated disease that it is susceptible to unique.

The genome of the domestic cat has been fairly well characterized, but a full understanding of the annotation of the cat’s genome is still lacking.

This cutting-edge project will improve our understanding of the annotation of the domestic cat genome in a wide variety of tissues/organs using recommendations developed by a consortium of researchers called the Functional Annotation of ANimal Genomes (FAANG). Such improved understanding will shed light not only on the genetic mechanisms of what makes a cat a cat, but also on the mechanisms of a variety of diseases of cats.

Importantly, the information gleaned about the genetic mechanisms of disease in this project has the strong potential to identify improved ways to diagnose, treat, and prevent a wide variety of feline diseases.

Investigator: Jessica Hayward BSc, MSc, PhD

The Uterine Response Following Ovarian Stimulation with Exogenous Hormones in the Domestic Cat: Providing Insight into the Success or Failure of Embryo Implantation in Endangered Felids

Most of the wild felids in the world are threatened with extinction, and captive breeding programs are vital to protecting their survival as species.

Assisted reproductive technologies (ARTs) such as artificial insemination and embryo transfer are important tools in these programs, as natural breeding of feline species in captivity is challenging.

Stimulation of the ovaries to produce greater numbers of ova (eggs)(ovulation) by administration of hormones is an important tool in the ARTs that are used in captive wild cats, but failure of pregnancy and low litter sizes are common after this stimulation, largely due to failure of implantation of the fertilized egg in the uterus.

Improving the success of captive-bred pregnancies induced by ARTs by advancing our understanding of the process of feline embryo implantation has tremendous potential to positively impact conservation efforts endangered feline species.

This study will compare the structural, immune, and molecular biologic changes that take place in the uterus of domestic cats following naturally stimulated ovulation to that seen with ovulation induced by hormone administration as a first step toward improving the success of ARTs in captive bred endangered wild cats.

Investigator: Ned Place PhD, MD

Walking epidural injection at the sacrococcygeal space for post-operative analgesia in cats undergoing ovariohysterectomy

Walking epidural anesthesia (WEA) involves the injection of drugs that inhibit the transmission of pain signals in the nervous system (i.e. pain “numbing” drugs) into the epidural space that surrounds the spinal cord.

This technique is commonly used in women and dogs undergoing surgery of the reproductive tract surgery to control post-operative pain, but a protocol for its use in cats has yet to be established.

The application of WEA has the potential to dramatically improve the recovery of many thousands of cats undergoing ovariohysterectomy (OVH : “spay”) each year.

This study will determine the appropriate volume and site of administration of pain-numbing drugs for the use of WEA in cats, and will then compare the recovery of cats undergoing OVH (recovery time, pain scores, side-effects) using standard general anesthesia and WEA to that seen in cats undergoing OVH using standard general anesthesia alone to determine whether WEA improves anesthetic recovery and comfort in cats following OVH.

This important step toward the development of a safe and effective WEA protocol for use in cats has the potential to dramatically decrease the discomfort experienced by cats undergoing OVH.

Investigator: Jordyn Boesch DVM, PhD, DACVAA

Short-sighted evolution and the coronavirus spike protein: feline coronavirus as a model for within-host changes influencing viral virulence and tropism

Feline infectious peritonitis (FIP) is a devastating disease of cats that is caused by a coronavirus that can exist in numerous forms in infected cats due to mutations that alter where it resides in the body (tropism) and its ability to cause disease (virulence). Previous work suggests that these mutations often take place in a portion of the virus called the spike protein, a key player in the virus’ ability to gain access to cells in the body of an infected cat.

While FIP has historically been viewed as occurring in two general syndromes (a wet form in which fluid accumulates in the body cavities and a dry form that is often characterized by neurologic problems), recent evidence suggests that the disease caused by coronaviruses in cats likely expands beyond this wet-dry form paradigm.

Recent evidence also supports the notion that feline coronavirus can exist undetected in different organ systems of the body of an infected cat and can undergo mutations that influence its ability to cause disease while residing in these “sanctuary sites”.

This study will use samples obtained from cats diagnosed with coronavirus infection that are suffering from diseases that do not fit into the classic wet-dry form model as a first step toward determining whether coronaviruses play a role in their development, and whether “sanctuary sites” play a role in promoting mutations in feline coronavirus that can change it tropism and virulence.

Investigator: Gary Whittaker PhD