
Kaori Sakamoto
VerifiedNorth Carolina State University · Population Health and Pathobiology
Active 1982–2026
About
Sarah Ho is the CVM Director of Student Engagement at the College of Veterinary Medicine at NC State University. Her role involves fostering student development and engagement within the college community. The page highlights her contact information and her position, emphasizing her leadership in student engagement and support, but does not provide specific details about her research focus, background, or key contributions in the field of veterinary medicine or biomedical sciences.
Research topics
- Medicine
- Biology
- Virology
- Immunology
- Genetics
- Internal medicine
- Microbiology
- Molecular biology
- Veterinary medicine
- Pathology
- Pharmacology
Selected publications
Research Square · 2026-05-18
preprintOpen accessParasitology Research · 2025-06-01
articleOpen accessDirofilaria immitis, also known as canine heartworm, contains an endosymbiont, Wolbachia, in all life stages. The antibiotic, doxycycline, has been incorporated into heartworm treatment protocols to eliminate Wolbachia. Previous studies indicate that subsequent infection cannot be established using viable third-stage larvae (L3) developed from doxycycline-treated microfilariae (mf). The stages in which the development of larvae is impacted by doxycycline remain unknown. We examined the impact of doxycycline on the third-stage to fourth-stage larval molt, as it is the first molt of D. immitis after it invades the vertebrate host. Microfilaremic blood was collected weekly from D. immitis-infected dogs with or without doxycycline treatment at 10 mg/kg as recommended by the American Heartworm Society. Blood was collected weekly until the end of doxycycline treatment. The blood was used for L3 production and mf isolation. Wolbachia levels in mf and L3 were measured using real-time quantitative PCR. L3 were cultured in vitro for 9 days to assess whether molting occurred. The Fisher's exact test and Bonferroni correction were used for statistical analysis. The molting of L3 from the doxycycline-treated groups did not show a significant difference compared to the L3 from the control group at weeks 0, 1, 2, 3, and 4. The Wolbachia levels in mf and L3 decreased starting from 7 days post-treatment and remained less than five percent of controls throughout the treatment. Doxycycline treatment can eliminate Wolbachia in both mf and subsequently developed L3. The molts of the mf to L3 in the mosquito and the L3 to L4 molt in vitro do not appear to be impacted by the reduction or elimination of Wolbachia.
bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-23
preprintOpen accessAbstract Roborovski dwarf hamsters are permissive for SARS-CoV-2 infection and progress to acute viral pneumonia with profound lung tissue injury, recapitulating hallmarks of severe COVID-19 in vulnerable patient groups such as older adults. In this study, we established dwarf hamster whole body plethysmography and assessed disease severity and propensity for long-term compromise of lung recovery from severe COVID-19-like disease in young, adult, and aged animals. Aged dwarf hamsters infected intranasally with variant of concern (VOC) omicron BA.4 experienced more severe clinical signs, carried a higher lung virus load, and had a greater risk of succumbing to infection. Resting airway hypersensitivity was transiently increased in aged, but not young, dwarf hamsters 3-4 days post infection (dpi). Pharmacologically induced respiratory distress revealed compromised lung capacity in animals of both age groups at peak disease. Aged animals showed impaired respiratory function for 45 days, mounted a weaker antiviral response, and developed chronic pneumonia with lasting tissue damage. Treatment of acute disease with approved antivirals, paxlovid-like nirmatrelvir+ritonavir or molnupiravir, prevented long-term respiratory sequelae in aged animals. Nirmatrelvir+ritonavir fully suppressed transient respiratory distress and mediated complete survival of aged animals. This study shows a high positive correlation between host age and SARS-CoV-2 disease severity in dwarf hamsters, establishes a model for chronic pneumonia with impaired respiratory capacity in at-risk hosts, and demonstrates benefit of antiviral therapy of acute disease for long-term respiratory health. Author Summary In the COVID-19 pandemic, the frequency of chronic respiratory insufficiency after acute SARS-CoV-2 infection was positively linked to patient age. Roborovski dwarf hamsters recapitulate hallmarks of life-threatening COVID-19 in at-risk patients that present with acute respiratory failure and prolonged respiratory incapacitation. In this study, we monitored disease progression and lung function in young and aged dwarf hamsters infected with a VOC omicron isolate and assessed the effect of antiviral treatment on long-term lung function. We established a strong correlation between host age and SARS-CoV-2 disease severity in dwarf hamsters, identified a high propensity of aged animals to develop chronic lung inflammation, and demonstrated a long-term loss of respiratory capacity in the subset of aged animals that survived the acute infection. Antiviral treatment suppressed the development of late sequelae and preserved lung function. These results have important implications for effective SARS-CoV-2 management in aged hosts at high risk of developing severe viral pneumonia with long-term impaired lung function.
Preprints.org · 2025-03-03 · 3 citations
preprintOpen accessBackground/Objectives: Adherence to treatment instructions is essential in managing chronic diseases related to obesity. One gene associated with adherence is the serotonin transporter (5-HTTLPR) gene, which has long (L) and short (S) alleles, resulting in LL, SL, and SS genotypes. Risk alleles for obesity include the R variant of the β3-adrenergic receptor (β3AR) and the G variant of uncoupling protein 1 (UCP1). This study aimed to evaluate whether the S/L variant of 5-HTTLPR, the R variant of β3AR, and the G variant of UCP1 are associated with adherence to a weight loss program. To assess the factors influencing adherence, eating behavior was evaluated using the Eating Behavior Questionnaire (EBQ). Methods: The study included 56 women with a mean age of 57.3±10 years and a mean BMI of 27.2±5.6 kg/m2. Long-read sequencing was used to analyze S/L mutations. Participants followed a six-month diet and exercise regimen for obesity management. Outcomes were assessed using clinical data and EBQ scores. Results: Participants were classified as SS (69.6%), SL (17.9%), or LL (12.5%). The R variant of β3AR was present in 34% of participants, with the G variant of UCP1 in 75%. After the intervention, SS participants showed significantly greater reductions in weight, body fat percentage, and waist circumference than LL participants (p < 0.05). Among EBQ items, significant improvements (p<0.05) were observed in SS participants for eating as a diversion, feeling of fullness, bad eating habits, unsteady eating patterns, and total EBQ score. In SL participants, only bad eating habits improved, whereas no significant changes were observed in LL participants. Obesity risk alleles did not significantly affect clinical outcomes. Conclusions: SS genotype participants demonstrated higher adherence to the weight loss program, leading to improved clinical outcomes and EBQ scores, independent of obesity risk genes.
Nutrients · 2025-03-20
articleOpen accessBackground/Objectives: Adherence to treatment instructions is essential in managing chronic diseases related to obesity. One gene associated with adherence is the serotonin transporter (5-HTTLPR) gene, which has long (L) and short (S) alleles, resulting in LL, SL, and SS genotypes. Risk alleles for obesity include the R variant of the β3-adrenergic receptor (β3AR) and the G variant of uncoupling protein 1 (UCP1). This study aimed to evaluate whether the S/L variant of 5-HTTLPR, the R variant of β3AR, and the G variant of UCP1 are associated with adherence to a weight loss program. To assess the factors influencing adherence, eating behavior was evaluated using the Eating Behavior Questionnaire (EBQ). Methods: This study included 56 well-educated and middle-class women with a mean age of 57.3 ± 10 years and a mean BMI of 27.2 ± 5.6 kg/m2. Long-read sequencing was used to analyze S/L mutations. Participants followed a six-month diet and exercise regimen for obesity management. Outcomes were assessed using clinical data and EBQ scores. Adherence was objectively measured by the reduction in body fat percentage. Results: Participants were classified as SS (69.6%), SL (17.9%), or LL (12.5%). The R variant of β3AR was present in 34% of participants, with the G variant of UCP1 in 75%. After the intervention, SS participants showed significantly greater reductions in weight and body fat percentage than LL participants (p < 0.05). Among EBQ items, significant improvements (p < 0.05) were observed in SS participants for eating as a diversion, feeling of fullness, bad eating habits, unsteady eating patterns, and total EBQ score. In SL participants, only bad eating habits improved, whereas no significant changes were observed in LL participants. Obesity risk alleles did not significantly affect clinical outcomes, though there may be small number bias. Conclusions: SS genotype participants demonstrated higher adherence to the weight loss program, leading to improved clinical outcomes and EBQ scores, independent of obesity risk genes.
Journal of Virology · 2025-08-11
articleOpen accessRoborovski dwarf hamsters are permissive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and progress to acute viral pneumonia with profound lung tissue injury, recapitulating hallmarks of severe coronavirus disease 2019 (COVID-19) in vulnerable patient groups such as older adults. In this study, we established dwarf hamster whole-body plethysmography and assessed disease severity and propensity for long-term compromise of lung recovery from severe COVID-19-like disease in young, adult, and aged animals. Aged dwarf hamsters infected intranasally with variant of concern (VOC) omicron BA.4 experienced more severe clinical signs, carried a higher lung virus load, and had a greater risk of succumbing to infection. Resting airway hypersensitivity was transiently increased in aged, but not young, dwarf hamsters 3-4 days post-infection. Pharmacologically induced respiratory distress revealed compromised lung capacity in animals of both age groups at peak disease. Aged animals showed impaired respiratory function for 45 days, mounted a weaker antiviral response, and developed chronic pneumonia with lasting tissue damage. Treatment of acute disease with approved antivirals, paxlovid-like nirmatrelvir + ritonavir or molnupiravir, prevented long-term respiratory sequelae in aged animals. Nirmatrelvir + ritonavir fully suppressed transient respiratory distress and mediated complete survival of aged animals. This study shows a high positive correlation between host age and SARS-CoV-2 disease severity in dwarf hamsters, establishes a model for chronic pneumonia with impaired respiratory capacity in at-risk hosts, and demonstrates the benefit of antiviral therapy of acute disease for long-term respiratory health.IMPORTANCEIn the COVID-19 pandemic, the frequency of chronic respiratory insufficiency after acute SARS-CoV-2 infection was positively linked to patient age. Roborovski dwarf hamsters recapitulate hallmarks of life-threatening COVID-19 in at-risk patients. In this study, we monitored disease progression and lung function in young and aged dwarf hamsters infected with a VOC omicron isolate and assessed the effect of antiviral treatment on long-term lung function. We established a strong correlation between host age and SARS-CoV-2 disease severity in dwarf hamsters, identified a high propensity of aged animals to develop chronic lung inflammation, and demonstrated a long-term loss of respiratory capacity in the subset of aged animals that survived the acute infection. Antiviral treatment suppressed the development of late sequelae and preserved lung function. These results have important implications for effective SARS-CoV-2 management in aged hosts at high risk of developing severe viral pneumonia with long-term impaired lung function.
The FASEB Journal · 2025-09-24 · 2 citations
articleOpen accessMitogen-activated protein kinase (MAPK) p38 plays a key role in driving the pathology of acute lung injury (ALI), but effective therapeutic targeting remains elusive. Atypical p38 signaling, mediated by interaction with the adaptor protein Tumor Growth Factor β Activated Kinase 1 (TAK1) Binding Protein 1 (TAB1), has so far only been observed during pathological responses, representing a selective and alternative target during pulmonary injury. However, atypical signaling has not been investigated in the context of pulmonary injury and immune responses related to the onset and progression of ALI. Here, we utilized a genetic knock-in mouse to block influenza A-induced lung injury mediated by atypical signaling. We report that the loss of TAB1-p38 interaction reduces weight loss and recovery time, reduces histopathological scores associated with influenza-induced lung injury early during infection, and prompts earlier recruitment of monocytes to the lungs following infection. These results were found to be independent of viral replication and infectivity, representing the first evidence for the roles of atypical signaling as a driver of host-mediated pulmonary injury following influenza infection.
Parasites & Vectors · 2025-02-26 · 1 citations
articleOpen accessBACKGROUND: Wolbachia is present in all life stages of Dirofilaria immitis. Wolbachia surface protein (WSP) can be highly immunogenic and induce acute inflammatory reactions in the host upon worm death. To avoid the abrupt release of Wolbachia and its antigens from deceased parasites, the American Heartworm Society (AHS) has recommended using doxycycline (DOXY) and having a 1-month wait period between the DOXY treatment and the adulticidal process for Wolbachia elimination. Studies have shown that the 28 day, 10 mg/kg twice daily (BID) administration of DOXY can effectively clear Wolbachia in the bloodstream of the host. The 1-month wait period is hypothesized to allow for further reduction of Wolbachia. However, the levels of Wolbachia in adult parasites after the DOXY treatment remain unknown. METHODS: Forty-five purposely bred dogs were intravenously transplanted with 20 Dirofilaria immitis adults, consisting of 12 females and 8 males. The dogs were divided into nine groups of five dogs each. Two groups each received 5, 7.5, or 10 mg/kg DOXY BID orally for 28 days, and ivermectin (IVM) monthly (6 µg/kg.) Three groups remained untreated as controls. Study animals were necropsied on day 0, day 30, and day 60, following the start of treatment. Adult worms were collected at necropsy and preserved for analysis. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry for WSP were performed on worms collected at each time point. The data were analyzed using a linear mixed model (LMM). Multiple comparisons were adjusted using Tukey's test. RESULTS: The qPCR results showed that all treatment doses significantly reduced Wolbachia levels compared with the control groups at 30 and 60 days. The intradose comparison indicated a significant decrease on day 60 compared with day 30. No significant differences were found between different doses on the two examination dates. Immunohistochemistry indicated the markedly reduced presence of Wolbachia in treatment groups. CONCLUSIONS: All DOXY dosages can be considered effective in reducing Wolbachia on both tested dates (30 and 60 days). On the basis of the further reduction of Wolbachia levels in adult D. immitis, the 1-month rest period in the AHS heartworm treatment guidelines is beneficial. Wolbachia can still be detected on day 60 in all dosage groups.
The Impact of Atypical MAPK p38 Signaling in Inflammatory Disease Progression in the Mouse Lung
Journal of Pharmacology and Experimental Therapeutics · 2024-05-13
articleNature Communications · 2024-02-08 · 11 citations
articleOpen accessMeasles cases have surged pre-COVID-19 and the pandemic has aggravated the problem. Most measles-associated morbidity and mortality arises from destruction of pre-existing immune memory by measles virus (MeV), a paramyxovirus of the morbillivirus genus. Therapeutic measles vaccination lacks efficacy, but little is known about preserving immune memory through antivirals and the effect of respiratory disease history on measles severity. We use a canine distemper virus (CDV)-ferret model as surrogate for measles and employ an orally efficacious paramyxovirus polymerase inhibitor to address these questions. A receptor tropism-intact recombinant CDV with low lethality reveals an 8-day advantage of antiviral treatment versus therapeutic vaccination in maintaining immune memory. Infection of female ferrets with influenza A virus (IAV) A/CA/07/2009 (H1N1) or respiratory syncytial virus (RSV) four weeks pre-CDV causes fatal hemorrhagic pneumonia with lung onslaught by commensal bacteria. RNAseq identifies CDV-induced overexpression of trefoil factor (TFF) peptides in the respiratory tract, which is absent in animals pre-infected with IAV. Severe outcomes of consecutive IAV/CDV infections are mitigated by oral antivirals even when initiated late. These findings validate the morbillivirus immune amnesia hypothesis, define measles treatment paradigms, and identify priming of the TFF axis through prior respiratory infections as risk factor for exacerbated morbillivirus disease.
Recent grants
NIH · $114k · 2007
NIH · $405k · 2015
Frequent coauthors
- 68 shared
Paola Cazzini
- 33 shared
Joerg Mayer
University of Georgia
- 33 shared
Nicole Gottdenker
University of Georgia
- 32 shared
James G. Fox
- 32 shared
Drury R. Reavill
Med Center
- 32 shared
N. Parry
- 32 shared
Megan K. Watson
Zoo Atlanta
- 25 shared
Heather R. Herd
University of Oklahoma Health Sciences Center
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