About

Mason C. Jager, DVM, PhD, DACVP, is an Assistant Professor in the Department of Population Medicine and Diagnostic Sciences at Cornell University College of Veterinary Medicine. His research focuses on host-pathogen interactions with a specific emphasis on viral pathogenesis. He is especially interested in the association of novel viruses with clinical disease, utilizing a combination of traditional pathology, molecular virology, and cell biology to study virus distribution, tissue tropism, and host factors required for disease progression. His laboratory investigates the replication dynamics of equine parvovirus-hepatitis, a novel virus linked to hepatitis and fatal hepatic necrosis in horses, along with other emerging viruses such as equine hepacivirus and skunk adenovirus. As an anatomic pathologist specialized in viral pathogenesis, he collaborates with researchers developing therapeutics and preventatives against viruses including Ebola, Nipah, Hendra, Influenza, and SARS-CoV-2.

Research topics

• Medicine
• Biology
• Virology
• Chemistry
• Genetics
• Biochemistry

Selected publications

• Pancreatic and biliary duct <i>Hammondia heydorni</i> infection in a dog fed a raw elk-meat diet

  Journal of Veterinary Diagnostic Investigation · 2026-02-13

  articleOpen accessSenior authorCorresponding

  We describe a 3-y-old Standard Poodle that was fed a raw elk-meat diet and developed anorexia, icterus, and markedly elevated liver enzyme activities. Histopathology of the pancreatic and liver biopsy specimens revealed lymphohistiocytic pancreatitis and hepatitis with intraepithelial protozoa. Histologically, Hammondia spp. are indistinguishable from Neospora caninum. Therefore, we employed PCR and amplicon sequencing to further investigate our case. Amplification and sequencing of the ITS1 marker matched 100% with Hammondia heydorni . Intrapancreatic involvement and the histopathologic features of hepatic and pancreatic H. heydorni infection have not been reported previously in dogs, to our knowledge. H. heydorni is a coccidian organism with an obligatory 2-host life cycle. The definitive hosts are dogs and coyotes; the intermediate hosts are mostly ruminants, including cervids. Ingesting tissue cysts within the skeletal muscle of the intermediate hosts leads to infection in the definitive hosts. H. heydorni has been considered clinically inconsequential; however, increasing reports note gastrointestinal and hepatic disease in dogs associated with this organism, and H. heydorni is considered an emerging pathogen in dogs. Infection in our case was associated with ingestion of raw cervid meat; cases of H. heydorni infection are invariably linked to ingestion of raw-meat diets.

  PublisherOA PDFDOI

• Deletion of a KSF Motif Attenuates NSP1 Host Cell Translation Shutoff and Impairs SARS-CoV-2 Virulence

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-17 · 1 citations

  preprintOpen access

  ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), triggered a global pandemic with profound social and economic consequences. The viral spike (S) protein has been identified as a key determinant of SARS-CoV-2 pathogenicity. In this study, we demonstrate that the Omicron BA.4 and BA.5 variants, which have closely related S proteins, exhibit different virulence in K18-hACE2 transgenic mice. A comparison of genomic sequences revealed key differences between variants BA.4 and BA.5, including a three amino acid deletion (ΔKSF) in the linker region of the non-structural protein 1 (NSP1) in BA.4. Using reverse genetic systems, we engineered a recombinant (r)SARS-CoV-2 BA.5 expressing BA.4 NSP1, which was significantly attenuated in vivo , similar to the natural BA.4 isolate, compared to rBA.5 wild-type (WT). This finding indicates that NSP1 is responsible, at least in part, for the differences in virulence between BA.4 and BA.5. Mechanistically, BA.4 NSP1 showed a reduced ability to inhibit host gene translation compared to BA.5 NSP1. Notably, a rSARS-CoV-2 WA1 original strain containing the same ΔKSF in NSP1 was also attenuated in vivo compared to rWA1 WT. Together, these findings highlight the contributions of the NSP1 linker region to inhibiting host gene expression and SARS-CoV-2 pathogenicity, as well as the feasibility of targeting NSP1 for the rational design of live-attenuated vaccines and/or antivirals. IMPORTANCE Understanding why some SARS-CoV-2 variants cause more severe disease than others is crucial for proper management or for the rational design of prophylactic and therapeutic treatments. While most studies focus on the spike (S) protein, we found that another viral protein, NSP1, also plays a key role in disease severity among SARS-CoV-2 variants. A small deletion in NSP1, present in the Omicron BA.4 variant, weakens the virus ability to shut down the host’s immune response, making BA.4 less severe than BA.5. When we introduced the same deletion into the original SARS- CoV-2 WA1 strain, the virus also became less harmful. This discovery suggests that NSP1 is an important virulence factor and supports the feasibility of targeting NSP1 for the development of new prophylactic and therapeutic treatments against SARS-CoV-2. By uncovering NSP1’s role in pathogenesis, our study provides insights that could help in designing better strategies to combat future variants of SARS-CoV-2.

  PublisherOA PDFDOI

• Myofibroblast differentiation in a cat with eosinophilic sclerosing fibroplasia involving mesenteric lymph nodes and liver

  Journal of Veterinary Diagnostic Investigation · 2025-05-12 · 1 citations

  articleOpen access

  Feline eosinophilic sclerosing fibroplasia (FESF) is a unique fibroproliferative disease of cats marked by eosinophilic inflammation and extensive tissue fibroplasia that affects the gastrointestinal tract predominantly. Biopsy specimens were examined from an 11-y-old, spayed female, domestic shorthair cat with a 1-2-mo history of vomiting and anorexia, abdominal lymphadenopathy, and multiple hepatic nodules. Microscopically, the liver nodules and enlarged mesenteric lymph node had profound eosinophilic inflammation and sclerosis characteristic of FESF; the stomach, duodenum, jejunum, and ileum were unremarkable. Immunohistochemistry (IHC) was performed to further characterize the cell populations. Increased intralesional mesenchymal cells, interpreted as reactive fibroblasts, were positive with antibodies against smooth muscle actin (SMA), indicating a myofibroblast phenotype. Abundant intralesional macrophages were ionized calcium-binding adapter molecule 1 (IBA1) immunolabeled. Dual IHC of SMA and IBA1 revealed several double-positive mesenchymal cells, suggesting macrophage-to-myofibroblast transition (MMT). Our findings underscore the important role of macrophages not only in chronic inflammation, but also in tissue repair and fibrosis. Our case was a unique presentation of FESF with primary liver and mesenteric lymph node involvement, and without overt gastrointestinal lesions. Additionally, to our knowledge, myofibroblast phenoconversion and MMT have not been reported previously in cats, giving new insights to the pathogenesis of this poorly understood disease entity.

  PublisherOA PDFDOI

• Chronic oral dosing of cannabidiol and cannabidiolic acid full-spectrum hemp oil extracts has no adverse effects in horses: a pharmacokinetic and safety study

  American Journal of Veterinary Research · 2025-01-09 · 7 citations

  articleOpen access

  OBJECTIVE: To compare the pharmacokinetics of cannabidiol (CBD) and cannabidiolic acid (CBDA) in horses and to evaluate the safety of their chronic administration. METHODS: CBD- and CBDA-rich oil (1 mg/kg) were administered orally twice daily to 7 adult horses over 6 weeks in a randomized, crossover design with a 2-week washout period. A 12-hour pharmacokinetic analysis was conducted on day 1 of each 6-week trial, followed by the measurement of peak and trough concentrations at weeks 1, 2, 4, and 6. The cannabinoids safety was assessed via daily physical examination, periodic bloodwork, and liver biopsy at the beginning and end of the study. RESULTS: 12-hour pharmacokinetics revealed a higher maximum serum concentration (103 vs 12 ng/mL) and greater area under the curve (259 vs 62 ng·h/mL) for CBDA when compared to CBD. Cannabidiolic acid nadir and peak serum levels over time ranged from 46 to 122 ng/mL, which was higher than CBD (12 to 38 ng/mL). Complete blood count and serum chemistry revealed no clinically relevant changes with either CBD or CBDA. No significant abnormalities were detected on liver ultrasonographic and histopathologic evaluation on day 0 and after both phases of the study. CONCLUSIONS: A dose of either 1 mg/kg of CBD or CBDA administered long term appears safe; however, CBDA serum concentrations suggest superior absorption/retention. CLINICAL RELEVANCE: Chronic cannabinoid supplementation in horses is safe. Considering the higher absorption of CBDA, its use is recommended to evaluate the therapeutic efficacy of this common hemp derived cannabinoid.

  PublisherDOI

• Integration of Domestic Cat Hepatitis B Virus DNA is Associated with Hepatocellular Carcinoma in Cats

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• Recurrent integration of domestic cat hepatitis B virus DNA near feline CCNE1 supports an oncogenic role in hepatocellular carcinoma in cats

  Tumour Virus Research · 2025-07-16 · 2 citations

  articleOpen access

  Hepatitis B virus (HBV) is the major cause of hepatocellular carcinoma (HCC) in humans. Domestic cat hepatitis B virus (DCHBV) naturally infects cats worldwide, but the oncogenic potential of this hepadnavirus is unclear. We investigated whether DCHBV contributes to feline HCC. Feline liver biopsies diagnosed with HCC (cases) and lymphocytic cholangitis (controls) were tested for DCHBV DNA by PCR. DCHBV-positive HCCs were further characterised by in situ hybridisation (ISH), whole-genome sequencing (WGS) and phylogenetic analysis. Targeted capture sequencing was used to identify and map viral DNA integrations. DCHBV DNA was detected in 17/71 (23.9%) HCCs versus 0/88 controls (P < 0.001). ISH confirmed hepatocyte-specific viral localization. Phylogenetic analysis placed six viruses in genotype A, and a seventh divergent virus in genotype B virus. Virus-host chimeric sequences, consistent with integration sites, were identified in 11/16 PCR-positive HCCs. Eight of the 11 integration sites were independently confirmed with WGS. Viral termini in integrated DCHBV sequences corresponded to double-stranded linear DNA, the substrate for HBV integration. Five unique DCHBV integrations fell within, or were adjacent to, the promoter of the feline homologue of proto-oncogene CCNE1 , a recurrent target for HBV integration in human HCC. Our findings reveal a compelling association between DCHBV detection and HCC in cats. Critically, virus integration in DCHBV-associated HCC is described for the first time, supporting that, like HBV, DCHBV can promote hepatocarcinogenesis by insertional mutagenesis. Clarification of fundamental DCHBV virology in vitro, and the consequences of natural infection could advance disease-prevention strategies for feline and human patients. • Domestic cat hepatitis B virus is associated with hepatocellular carcinoma in cats • Targeted capture sequencing reveals DCHBV integration in the cancer cell genome • Cyclin E1 protooncogene, CCNE , is a target for feline and human HBV cancer • Clarification of the clinical consequences of natural DCHBV infection is needed • Future studies DCHBV could inform feline and human hepatology

  PublisherDOI

• Footprint-free induced pluripotent stem cells can be successfully differentiated into mesenchymal stromal cells in the feline model

  Stem Cell Research & Therapy · 2025-04-20

  articleOpen access

  BACKGROUND: Induced pluripotent stem cells (iPSCs) can propagate indefinitely and give rise to every other cell type, rendering them invaluable for disease modelling, drug development research, and usage in regenerative medicine. While feline iPSCs have been described, there are currently no reports on generating genome integration (footprint)-free iPSCs from domestic cats. Therefore, the objective of this study was to generate feline iPSCs from fetal fibroblasts using non-integrative Sendai virus (SeV) vectors carrying human transcription factors. Moreover, these iPSCs were differentiated into mesenchymal stromal cells (MSCs), which can be used as an alternative to tissue-derived MSCs. METHODS: Feline fetal fibroblasts were transduced with CytoTune-iPS 2.0 Sendai Reprogramming vectors at recommended multiplicity of infections (MOI) and cultured for about 6 days. At 7 days post transduction cells were dissociated, replated on inactivated feeder cells and maintained in iPSC medium for 28 days with daily medium change. Emerging iPSC colonies were mechanically passaged and transferred to fresh feeder cells and further passaged every 6-8 days. Four feline iPSC lines were generated, with two selected for further in-depth characterization. Feline iPSCs were then differentiated into MSCs using a serial plating strategy and an inhibitor of the transforming growth factor-β (TGF-β) type I receptor. RESULTS: Feline iPSCs exhibited characteristic colony morphology, high nuclear-to-cytoplasmic ratio, positive alkaline phosphatase activity, and expressed feline OCT4, SOX2, and Nanog homeobox (NANOG) stem cell markers. Expression of SeV-derived transgenes decreased during passaging to be eventually lost from the host cells and feline iPSCs could be stably maintained for over 35 passages. Feline iPSCs differentiated into embryoid bodies in vitro and did not form fully differentiated teratomas; instead, they generated in vivo masses containing mesodermal tissue derivatives when injected into immunodeficient mice. Feline iPSC-derived MSCs were plastic adherent, displayed MSC-like morphology, expressed MSC-specific surface markers, and differentiated into cells from the mesodermal lineage in vitro. RNA deep sequencing identified 1,189 differentially expressed genes in feline iPSC-derived MSCs compared to feline iPSCs. CONCLUSION: We demonstrated the generation of footprint-free iPSCs from domestic cats and their directed differentiation potential towards MSCs. These SeV-derived feline iPSCs and iPSC-derived MSCs will provide valuable models to study feline diseases and explore novel therapeutic strategies and can serve as translational models for human health, leading to increased knowledge on disease pathogenesis and improved therapeutic interventions.

  PublisherOA PDFDOI

• Replication-incompetent VSV-based vaccine elicits protective responses against SARS-CoV-2 and influenza virus

  Science Advances · 2025-01-29 · 4 citations

  articleOpen access

  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses lead to severe respiratory illnesses and death in humans, exacerbated in individuals with underlying health conditions, remaining substantial global public health concerns. Here, we developed a bivalent replication-incompetent single-cycle pseudotyped vesicular stomatitis virus vaccine that incorporates both a prefusion-stabilized SARS-CoV-2 spike protein lacking a furin cleavage site and a full-length influenza A virus neuraminidase protein. Vaccination of K18-hACE2 or C57BL/6J mouse models generated durable levels of neutralizing antibodies, T cell responses, and protection from morbidity and mortality upon challenge with either virus. Furthermore, the vaccine provided heterologous protection upon challenge with a different influenza virus strain, supporting the advantage of using NA to increase the breadth of vaccine protection. Now, no bivalent vaccine is approved for use against both SARS-CoV-2 and influenza virus. Our study supports using this platform to develop safe and efficient vaccines against multiple viruses.

  PublisherDOI

• Broad-spectrum synthetic carbohydrate receptors (SCRs) inhibit viral entry across multiple virus families

  Science Advances · 2025-08-27 · 5 citations

  articleOpen access

  Viral pandemics continue to threaten global health and economic stability. Despite medical advances, the absence of broad-spectrum antivirals (BSAs) prevents rapid responses to emerging viral threats. This is largely due to the lack of universal drug targets across diverse viral families and high variability among viral proteins. In this study, we evaluated 57 synthetic carbohydrate receptors (SCRs) for antiviral activity in cellulo using pseudotyped virus particles (PVPs) from six high-risk viruses across three families: Paramyxoviridae, Filoviridae, and Coronaviridae. Four SCRs inhibited all tested PVPs, and their efficacy was confirmed against live viruses including SARS-CoV-2, MERS-CoV, EBOV, MARV, NiV, and HeV. Notably, SCR005 and SCR007 , which exhibited minimal toxicity, significantly reduced SARS-CoV-2 infection in a severe animal model with a single dose. Mechanistic studies suggested that SCRs bind viral envelope N-glycans, blocking viral attachment and/or fusion. These results identify conserved viral N-glycans as promising BSA targets and establish SCRs as candidate prophylactic agents against enveloped viruses with pandemic potential.

  PublisherDOI

• Neonatal CD8+ T Cells Resist Exhaustion during Chronic Infection

  The Journal of Immunology · 2024-01-17 · 4 citations

  articleOpen access

  Chronic viral infections, such as HIV and hepatitis C virus, represent a major public health problem. Although it is well understood that neonates and adults respond differently to chronic viral infections, the underlying mechanisms remain unknown. In this study, we transferred neonatal and adult CD8+ T cells into a mouse model of chronic infection (lymphocytic choriomeningitis virus clone 13) and dissected out the key cell-intrinsic differences that alter their ability to protect the host. Interestingly, we found that neonatal CD8+ T cells preferentially became effector cells early in chronic infection compared with adult CD8+ T cells and expressed higher levels of genes associated with cell migration and effector cell differentiation. During the chronic phase of infection, the neonatal cells retained more immune functionality and expressed lower levels of surface markers and genes related to exhaustion. Because the neonatal cells protect from viral replication early in chronic infection, the altered differentiation trajectories of neonatal and adult CD8+ T cells is functionally significant. Together, our work demonstrates how cell-intrinsic differences between neonatal and adult CD8+ T cells influence key cell fate decisions during chronic infection.

  PublisherOA PDFDOI

Frequent coauthors

• Hector C. Aguilar

  Cornell University

  28 shared

• David W. Buchholz

  New York State College of Veterinary Medicine

  26 shared

• Brian Imbiakha

  Cornell University

  22 shared

• Julie Sahler

  Cornell University

  17 shared

• Avery August

  Cornell University

  17 shared

• Gary R. Whittaker

  Curtin University

  16 shared

• Gerlinde R. Van de Walle

  Cornell University

  16 shared

• I. Abrrey Monreal

  Cornell University

  13 shared

Education

• Residency in Veterinary Anatomic Pathology, College of Veterinary Medicine

  Cornell University

  2018

• Doctor of Veterinary Medicine, College of Veterinary Medicine

  Cornell University

  2012

• Bachelor of Science, Pathobiology

  University of Connecticut

  2008

Awards & honors

• ACVP Young Investigator Poster Award in the Natural Disease…