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A $2 million grant from the Mass Life Sciences Center has helped launch the Comparative Pathology and Genomics Shared Resource at Cummings School of Veterinary Medicine, a shared resource with state-of-the-art equipment that fills newly renovated laboratory space. For Cheryl London, a veterinary oncologist and Associate Dean for Research and Graduate Education, it represents a long-time vision becoming reality.

“Understanding the pathology of infectious diseases is more critical than ever,” said London, who added that the resource will lead to improvements in the treatment and prevention of diseases in humans through detailed genetic characterization of model systems and the associated pathology across species.

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London tapped two Cummings School faculty members to lead the effort: assistant professor Amanda Martinot, a veterinary pathologist who focuses on infectious diseases such as SARS CoV-2 and tuberculosis, and assistant research professor Heather Gardner, GBS20, a veterinary oncologist and geneticist.

Cummings School has been investing in this goal for quite some time. In 2020, the 7,500-square-foot Peabody Pavilion was renovated into modern, flexible lab space designed to support multidisciplinary teams. In addition, the resource will leverage Tufts resources such as the New England Regional Biosafety Laboratory (RBL).

“When fully operational, this resource will offer advanced capacities for credentialling and analyzing animal models of disease that will help to grow collaborative opportunities among regional academic and industry entities; provide training opportunities for students, fellows, scientists and clinicians; and ultimately support job growth through expansion of the research enterprise in Central Massachusetts,” said London.

Projects in the Pipeline

Martinot's research has focused on tuberculosis (TB). When the Martinot Lab and her collaborators—Cummings School assistant professor Gillian Beamer, Tufts University School of Medicine associate professor Bree Aldridge, and Harvard University professor Peter Sorger, head of the Harvard Program in Therapeutic Sciences—identified some rare lung biopsies and archived lung specimens from tuberculosis patients that were taken during autopsies many years ago, Martinot thought they were a natural pilot project for the Comparative Pathology and Genomics Shared Resource.

“We're trying to understand the biology of tuberculosis in human tissue, what helps the body clear TB, and what fuels TB progression,” said Martinot. “We use a lot of animal models to try to understand these processes, but there's no animal model that perfectly mimics human TB disease.”

The resource's new technology can extract meaningful genetic information from the immune cells surrounding and within granulomas, a hallmark pathologic feature of tuberculosis—something they haven't been able to do before. This technology also will allow them to obtain similar information from a variety of pathology samples.

Another pilot project aims to advance research by London and Gardner in canine osteosarcoma, an aggressive bone cancer that affects more than 25,000 dogs each year. In 2019, they published findings of a study that detailed the landscape of genetic mutations in canine osteosarcoma, and more recently completed a clinical trial to test a new immunotherapy treatment on dogs diagnosed with this type of cancer. The Clinical Trials Office at Cummings School has treated a number of canine osteosarcoma patients, allowing banking of associated biologic samples for further investigation. With these tissue samples, investigators can ask questions about the molecular and genomic features of cancer over time and identify clinical and pathologic correlates.

“Animals get a lot of the same diseases that people do, and the information we learn from animals with these diseases can inform investigation of novel research opportunities across species,” said Gardner.

“We can start to interrogate the combination of pathology with genetics and follow how the cancer is mutating,” Martinot said. “And we can look at where these cancer cells live to try to understand how the microenvironment might be supporting the progression of the cancer. That information could lead to potential treatment options.”

Paul Mathew, an oncologist at Tufts Medical Center and an associate professor at Tufts School of Medicine, is interested in using the resource's technology to ask similar questions about prostate cancer using biopsies from human patients. He wants to understand the tumor and how the microenvironment changes over time in prostate cancer patients. The School of Medicine is one of many potential users of the resource—others include UMass Medical School and Medical Center, which has plans for a new Veterans Administration outpatient clinic and Institute for Human Genetics.

The Technology Inside

The resource is home to “cutting edge new technology that integrates pathology and genomics,” said Martinot. “With the help of this grant, we can do whole genome sequencing for genetic analysis of pathogens, tumors, and anything imaginable where the DNA sequence might make a difference.”

The goal is to help drive discovery, adds Gardner. “We have equipment to support next generation sequencing projects, such as a liquid handler robot to help automate sample processing and an Illumina sequencer. We also have a suite of NanoString equipment, which is a platform that will allow increased use of samples historically considered difficult to work with, including formalin-fixed samples, which are often very degraded.”

The new technology that will power this effort falls into two main categories:

Highly multiplexed immunofluorescence imaging, which combines the microscopic study of tissue samples with high-dimensionality analysis tools. Martinot's lab members are currently training in the Sorger Laboratory at Harvard to apply a specific form of this technology, tissue cyclic immunofluorescence (t-CyCIF), to animal models of infectious disease.
Next Generation Sequencing and Nanostring Technology, which includes short-read sequencing, single-cell sequencing, and digital spatial profiling capabilities.

Everyone involved with the shared resource is excited about its future potential and the opportunity to see it grow. As Gardner said, “The opportunities to impact research, in all areas, are limited by the investigators' imagination.”

Read more at Tufts University.

The post Vet School Receives Grant To Invest In The Power Of Pathology And Genomics appeared first on Horse Racing News | Paulick Report.

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Recent developments in the U.S. on the 140-mare cap introduced by The Jockey Club on stallion coverings, and the subsequent lawsuits filed by Ashford Stud, Spendthrift Farm and Three Chimneys Farm, should be a wake-up call for owners and breeders in Europe. The justifications from both sides of the debate raise some interesting questions that must be addressed for the future of the industry.

The Jockey Club's rationale for implementing the cap is that it is “formulating a rule that will promote diversity of the Thoroughbred gene pool and protect the long-term health of the breed.” Taken at face value this seems a reasonable and noble move to protect the future of the Thoroughbred horse and the racing industry. The response from the three studs taking legal action is that the cap “serves no legitimate purpose and has no scientific basis,” while also alleging that the nine stewards of The Jockey Club who voted to adopt the rule change did so based more on a desire to satisfy their own “conflicting economic interests” rather than the organisation's stated purpose of “facilitating the soundness of the Thoroughbred breed.” Again, a reasonable counter-argument. So how will this be resolved?

Let us be clear, the 'industry' as a whole needs the likes of Ashford Stud et al to continue to be economically viable to drive the industry forward, as their success is a reflection of the horses that they race or purchase and develop as stallions. Their success feeds down to all levels of the racing and breeding industry, and we should be mindful of not disrupting that success. However, the raison d'etre of racing and breeding is to improve the Thoroughbred breed and to promote high-ability athletes while maintaining a viable and robust horse population. The topic of inbreeding is often discussed and explored by breeders the world over, with many successful examples of it having a positive effect on some high-profile individuals, namely Danehill, or more recently Zoustar (Aus), amongst others. But ultimately breeders, studs and The Jockey Club have no real data on how any consequences of inbreeding manifest in the horse population. There is very little research into the impact of inbreeding, or line breeding, and thus a poor understanding of the impact on the breed caused by stallions covering large books of mares. There is just the general assumption that continued inbreeding or limiting the gene pool is detrimental to the Thoroughbred and its soundness. But is that true? Where are the data and the studies? Where are the facts?

There is only one answer to these questions. To finally understand the impact of the likes of Northern Dancer and whether his ubiquity has positively or negatively impacted the breed, to know for sure if the continued increasing book sizes of the elite proven stallions is detrimental to the racehorse: that answer is genomics. Population-scale genomics of the Thoroughbred. And it needs to start now.

Genomics and DNA sequencing are powerful tools widely used to understand the influence of genetic variation on gene expression, as well as helping to understand the genetics behind medical conditions. There are good reasons this should be supported by all sides of the industry and will ultimately benefit the industry as a whole, including studs and breeders at every level.

Practically speaking, the study needs to begin with each new generation of foals, this being the easiest point to capture and gather data. A small blood sample would be taken and sent for DNA sequencing. This only needs to be captured once for each individual horse and the cost for the British foal crop, working on an individual sample cost of £600-£800, would be roughly in the region of £3 million per year.

In the interests of preserving the longevity of the sport, and circumventing the suggestion of a similar situation in Europe to what we are seeing in the U.S., funding for the study should come from all corners of the industry and be weighted towards the areas of the industry that profit the most from the sport of racing. Namely, bookmakers, the BHA, The Jockey Club, stud farms, auction houses, vet practices…and the list goes on.

So why would this benefit the industry?

If a study indicates that the large books of successful stallions, and the subsequent increase of inbreeding and lack of genetic variation causes a negative impact on a horse's welfare, either manifested as reduction in soundness or by increased medical conditions, then without any action from studs and breeders the long-term business of racing will be at risk. Taking no action would result in a weaker horse in generations to come, and pressure from the public, and especially animal welfare organisations, would be at an all-time high. By following the data and using such a study to support corrective actions and future decision-making the industry could head off any potential problems before they hit.

Alternatively, if a study indicates the opposite, that large stallion books do not lead to limited genetic variation manifesting as reduced soundness or medical conditions, then again we will have the data and factual evidence to support the strategy of continuing with the status quo.

Either result is of importance and benefit to studs, breeders and racing in general; so much so, that without such a genomics study being initiated, we are likely to see the studs' business model being at risk with or without an enforced mare cap–either by genetic problems affecting future generations, or by a strict limiting of their stallions' book sizes.

Clearly the key to the success of a genetic study of the Thoroughbred is gathering as much data as possible, and this isn't going to provide quick answers. It's a long-term project, and likely as long as 10 to 20 years would be necessary to gather enough data to truly understand the impact of large book sizes. To compliment the genetic data, there would be a need for a method to capture the health and ability of each individual horse throughout its life. We already have handicapper ratings to guide us on ability levels of each horse that races, but more importantly there needs to be a way to capture indications of medical unsoundness or health conditions, especially for horses that do not make it to a racecourse. Ideally, the responsible party for recording these health data points should be the veterinarians who are the subject matter experts on these issues, as they already have the training and ability to categorise any abnormalities or medical conditions. The creation of a database cataloguing these details would make it easy for vets to update the information any time a horse's condition changes.

A large-scale Thoroughbred genomics study of this nature would revolutionise the conversation on breeding and settle any arguments on the risks of inbreeding and stallion book sizes. It would be a proactive, data-driven approach to tackling the topic, and prevent any decisions being made based on uninformed opinion or bias. Such a study would help guide ruling bodies such as the BHA and The Jockey Club, give data and resources to the studs and breeders, and ensure the welfare and success of the Thoroughbred racehorse for generations to come.

Greg Saveall-Green is a Thoroughbred breeder and works in the field of genomics.

The post Op/Ed: The Need For Data appeared first on TDN | Thoroughbred Daily News | Horse Racing News, Results and Video | Thoroughbred Breeding and Auctions.

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