The Laminitis Laboratory at New Bolton Center

12/14/2021

Ancient DNA reveals the long-sought homeland of modern horses

More fascinating horse research.

Bronze Age riders trotted out their new mounts in the western Eurasian steppe

12/01/2021

Breakthrough Laminitis Research Opens Potential New Avenues For Treatment - Horse Racing News | Paulick Report

Thank you to the UF and Penn Vet communications teams, who ALSO collaborated to craft this press release, picked up by Paulick Report: https://www.paulickreport.com/horse-care-category/breakthrough-laminitis-research-opens-potential-new-avenues-for-treatment/

Horse owners usually dread hearing the diagnosis of “Laminitis.” The disease plagues horses of many backgrounds, ages and disciplines. Using genetics, UF/IFAS and University of Pennsylvania School of Veterinary Medicine scientists have made a breakthrough in the disease thanks to funding from Th...

11/29/2021

Transcriptome diversity and differential expression in supporting limb laminitis

Excited to see this collaborative project with Samantha Brooks and Heather Holl at U Florida published. Purified mRNA was provided by the Laminitis Discovery Database in the Galantino-Homer Laminitis Lab from supporting limb laminitis (SLL) cases (including samples both from feet with primary, severe SLL of 1-7 days duration and those with very early, often secondary "developmental" SLL) age-matched controls (all Thoroughbreds currently or recently in race training at the time of injury) and the transcriptomic sequencing and data analysis were performed at UF. The results complement and extend our studies of cell stress and stress response and the IL-17A inflammatory pathway in SLL. This project was funded by The Foundation for the Horse (formerly the American Association of Equine Practitioners Foundation).

Edit: Free access for 50 days here: https://authors.elsevier.com/c/1e8apbacHh~3t

Laminitis results in impaired tissue integrity and Inflammation of the epidermal and dermal lamellae connecting the hoof capsule to the underlying dis…

09/21/2021

Continuous digital hypothermia reduces expression of keratin 17 and 1L-17A inflammatory pathway mediators in equine laminitis induced by hyperinsulinemia

New paper from our group examines the contribution of keratinocyte activation and the IL-17 pathway (important in asthma and psoriasis) to inflammation in a model of endocrinopathic laminitis and the ability of distal limb cooling to block it. (free access to this link for 50 days)

The euglycemic hyperinsulinemic clamp model (EHC) of equine endocrinopathic laminitis induces rapid loss of lamellar tissue integrity, disrupts kerati…

02/24/2021

Laminitis Lab collaborator, Lynne Cassimeris (Lehigh U) generated this HoofSearch cover art using a lamellar tissue confocal microscopy image with our WGA lectin counterstain and then pseudocolored on her iPad. This and other art is available on many items at the Cassimeris Lab Redbubble shop, 100% of profits go to our collaborative research.

This is actually the abaxial (hoof end) of the lamellae with the hoof wall toward the top of the image and the center of the image being the center of the primary dermal lamella.

The cover of the January 2021 edition of HoofSearch explodes with the neon filtered microscopy of #laminitis researcher Dr. Lynne Cassimeris of Lehigh University, who captured the stunning detail of a tip of a single lamella from a horse's foot. Inside, listings and links to 83 new peer-reviewed articles published in January are organized by subjects from anatomy to zoo animals. Subscribers: Watch for your link coming this evening!

12/14/2020

Researchers shine spotlight on damaging inflammation in laminitis - Horsetalk.co.nz

Thank you to Horsetalk.co.nz for this write-up!
https://www.horsetalk.co.nz/2020/12/14/researchers-damaging-inflammation-laminitis/

Similarities seen to the human skin condition psoriasis.

12/11/2020

Interleukin-17A pathway target genes are upregulated in Equus caballus supporting limb laminitis

Our paper on IL-17 signaling in naturally-occurring Supporting Limb Laminitis was published in PLOS One today! This is open access, so go check it out.

IL-17 signaling is important in a few human diseases you may be familiar with: Psoriasis, psoriatic arthritis, Inflammatory Bowel Disease, and acute lung injury associated with COVID-19. Researchers are suggesting that FDA-approved immunomodulatory drugs that are widely used to treat psoriasis should be used for COVID-19 clinical trials. IL-17 is a biomarker of lung injury in COVID-19, with an area under the receiver operating curve score of 0.926, indicating a very good ability to distinguish between severe and mild COVID-19 cases (Liu, Y et al. 2019-novel coronavirus (2019-nCoV) infections trigger an exaggerated cytokine response aggravating lung injury ChinaXiv (2020).

And if you think that the colorized lamellae shown in Fig 1 would look cool on a cell phone case, t-shirt, mug, etc, go to the Cassimeris Lab Redbubble page for many lamellae-themed holiday gift ideas (100% of earnings go to laminitis research; link in first comment).

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232920

Supporting Limb Laminitis (SLL) is a painful and crippling secondary complication of orthopedic injuries and infections in horses, often resulting in euthanasia. SLL causes structural alterations and inflammation of the interdigitating layers of specialized epidermal and dermal tissues, the lamellae...

04/28/2020

Interleukin-17 pathway activation in Equus caballus supporting limb laminitis

We have a pre-print (not yet peer-reviewed, submitted to PLoS One) out on inflammatory pathway signaling in naturally-occurring Supporting Limb Laminitis cases from the Laminitis Discovery Database. The IL-17 pathway is also active in human psoriasis, inflammatory bowel disease, and equine asthma. In all cases, tissue damage sets off an inflammatory response that sets off a positive feedback loop.

https://www.biorxiv.org/content/10.1101/2020.04.27.063800v1

Supporting Limb Laminitis (SLL) is a painful and crippling secondary complication of orthopedic injuries and infections in horses, often resulting in euthanasia. Due to altered weight bearing, SLL causes structural alternations and inflammation of the interdigitating layers of specialized epidermal....

04/20/2020

How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes

I'm sure many of you are seeing the horrifying reports about organ failure in severe COVID-19 cases. This is an excellent article about the current understanding of how the disease may call organ failure. I had not heard about the effect on fingers and toes, but had already been thinking about the parallels with sepsis-associated laminitis. Access to this article is free.

"Reports are emerging of ischemia in the fingers and toes—a reduction in blood flow that can lead to swollen, painful digits and tissue death."

Laminitis Research at New Bolton Center currently involves writing and other remote tasks as the labs are shut down. I have also been making masks for our hospital and essential diagnostic laboratory personnel who are helping to keep our animals and food supply safe. Stay safe and sane. -Dr HGH

https://www.sciencemag.org/news/2020/04/how-does-coronavirus-kill-clinicians-trace-ferocious-rampage-through-body-brain-toes?utm_campaign=news_daily_2020-04-17&et_rid=17052573&et_cid=3290441

The lungs are ground zero for COVID-19, but blood clots may play a surprisingly big role in severe illness

03/03/2020

CassimerisLab Shop | Redbubble

Do you want to support laminitis research AND own some truly unique and functional "equine art"?

Laminitis Lab collaborator, Lynne Cassimeris of Lehigh U, has launched a Redbubble page where you can purchase equine lamellar tissue microscopy image-based art on mugs, phone cases, shirts, etc.

100% of proceeds go to Lehigh-Penn collaborative laminitis research projects.

Check it out! Tell your friends!

https://www.redbubble.com/people/cassimerislab/shop?artistUserName=cassimerislab

CassimerisLab is an independent artist creating amazing designs for great products such as t-shirts, stickers, posters, and phone cases.

01/27/2020

Just a moment...

Interesting study from colleagues at New Bolton Center about the impact of in-person caretaker visits on discomfort assessment in equine orthopedic patients. The take-home message is that remote monitoring may be needed to more accurately detect discomfort in horses. Catie Torcivia is a Research Fellow in the van Eps Laminitis Lab. Nice work!

https://www.mdpi.com/2076-2615/10/2/210/htm?fbclid=IwAR1dN50fNVMHgk3gqL9cmyqd26nZ5jPfi-dPj-tDVFkm1bYWXNh6dnvP-XQ

10/25/2019

The Laminitis Laboratory at New Bolton Center updated their business hours.

The Laminitis Laboratory at New Bolton Center updated their business hours.

10/25/2019

The Laminitis Laboratory at New Bolton Center updated their phone number.

The Laminitis Laboratory at New Bolton Center updated their phone number.

09/24/2019

The expression of equine keratins K42 and K124 is restricted to the hoof epidermal lamellae of Equus caballus

We are pleased to announce that our paper demonstrating that K124 and K42 are lamellar-specific keratins (the major structural proteins of the hoof capsule and lamellae) is now published and is freely available at the link below. For the first time in any species, we have produced and validated monoclonal antibodies against a nail unit-specific keratin isoform, K124, which is restricted to the lamellae and absent from the coronet, haired skin, chestnut, tongue, cornea, oral mucosa, and unhaired skin. Current projects are investigating the use of these antibodies in other species and as a lamellar-specific biomarker.

We thank our collaborators at Lehigh University, Cornell University, and University of Florida and the foundations that supported the Laminitis Discovery Database and this study, including the Laminitis Research Fund and Tamworth Trust at Penn Vet, Lehigh University Faculty Incentive Grant, Animal Health Foundation, the American Association of Equine Practitioners Foundation, Grayson-Jockey Club Research Foundation, and the Bernice Barbour Foundation, Inc.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219234

The equine hoof inner epithelium is folded into primary and secondary epidermal lamellae which increase the dermo-epidermal junction surface area of the hoof and can be affected by laminitis, a common disease of equids. Two keratin proteins (K), K42 and K124, are the most abundant keratins in the ho...

06/20/2019

I am very pleased to announce that a pre-print (submitted to PLOS ONE, but has not yet been peer-reviewed or accepted for publication) of our paper, "The expression of equine keratins K42 and K124 is restricted to the hoof epidermal lamellae of Equus caballus," is available for view/share/comment here:

https://www.biorxiv.org/content/10.1101/678102v1

These keratins are the major cytoskeletal proteins in the hoof lamellae and therefore account for most of the mechanical strength of the epidermal lamellar epithelium. We had first described them in 2010 and have since used several methods to characterize their expression.

We also generated monoclonal antibodies that specifically recognize one of the isoforms, K124, and can be used for future research and diagnostic applications. K124 is found in the secondary epidermal lamellae and is absent from the hoof coronet, haired skin, chestnut, cornea, oral mucosa, tongue, and glabrous skin.

This work represents a multi-year collaboration between investigators at Penn, Lehigh University, Cornell CVM, and the University of Florida, with excellent assistance from genscript.com.

Please share and go to the website to download and comment there. Editors and reviewers pay attention to visits/downloads/comments in determining interest in the submitted paper.

-Dr. Hannah Galantino-Homer

06/17/2019

Very short-handed in the lab, but I found some time today to finally provide histopathology images to go along with the earlier post showing normal, “laminitic/sinker” and “laminitic/rotation” feet.

These are typical examples of the microanatomy of feet like those from the Laminitis Discovery Database. As usual, these are meant to be educational, so please share and use, but please attribute to the Laminitis Laboratory at New Bolton Center. – Dr. Galantino-Homer

White asterisk marks the keratinized axis of a primary epidermal lamella in each image. All top images are the same low magnification and all lower images are the same higher magnifications except for the last one on the right, which is higher magnification than the other three.

“Normal”: LAM 84 RF, 2 yr TB gelding with other orthopedic problems. Upper image: Low magnification, lower image: higher magnification.

“Laminitic: Sinking”: LAM 118 LF, 2 yr TB filly with supporting limb laminitis due to a non-weight-bearing injury in the RF. Catastrophic failure of the suspensory apparatus of the distal phalanx with complete stripping of the secondary epidermal lamellar basal cells off of the keratinized axis and suprabasal cells (in other words, failure is mostly occurring between epidermal cells rather than at the basement membrane). Higher magnification image shows basal cells of secondary epidermal lamellae (yellow arrowhead) pulling away from necrotic/cornified suprabasal cells (black arrowhead) and keratinized axis in the less affected RF foot, which was developing secondary supporting limb laminitis.

“Laminitic: Rotation, Lamellar Wedge”: Images on the left are from LAM 140 LF, 14 yr TBxWB mare with PPID/Cushing’s, obesity, and regional adiposity (“cresty neck”). Images on the right are from LAM 109 RF, 9 yr QH mare with equine metabolic syndrome. Both had chronic laminitis with rotation of the distal phalanx relative to the hoof capsule, lamellar wedge, and founder rings. Yellow band indicates widening of the keratinized axis to form “lamellar wedge” of abnormal cornified tissue (lighter pink stain). Green asterisk shows gap with necrotic material and serum that often allows bacteria to track up from the ground surface to cause abscesses, inflammation, and pain. Circles adjacent to serum/necrotic area are forming “cap horn tubules” and contributing to the lamellar wedge. Green arrowhead shows an epidermal island that has detached from a secondary epidermal lamella. Blue arrowheads indicate areas of necrotic/apoptotic lamellar cells and loss of normal microanatomy. These cases were used in our recently published ER Stress in Endocrinopathic Laminitis study.

03/29/2019

A slide that I made for a recent Penn Vet Equine Club talk to explain why there are so many laminitis causes. As usual, please share and copy for educational purposes, as long as you keep the credit at the bottom of the slide.

I find it helpful to consider laminitis as an organ failure of the suspensory apparatus of the distal phalanx, that it occurs when a threshold for laminitis is passed, and that various intrinsic and extrinsic factors can move the lamellae toward the threshold for laminitis (red) or away from it and toward health (green). Some intrinsic factors (in blue) also lower the threshold itself so that a smaller push toward disease is needed to cause laminitis.

Multiple factors can be acting at once and the outcome is determined by their net positive (away from threshold, toward health) and negative (toward threshold) impacts on lamellar tissues.

SADP: Suspensory apparatus of the distal phalanx