A5084233018- Parasitic Infections and Diagnostics
- Viral gastroenteritis research and epidemiology
- Coccidia and coccidiosis research
- Amoebic Infections and Treatments
- Veterinary medicine and infectious diseases
- Clostridium difficile and Clostridium perfringens research
- Pneumocystis jirovecii pneumonia detection and treatment
- Toxoplasma gondii Research Studies
- Antimicrobial Peptides and Activities
- Helminth infection and control
- Research on Leishmaniasis Studies
- Malaria Research and Control
- Allergic Rhinitis and Sensitization
- Synthesis and Biological Evaluation
- Trypanosoma species research and implications
- Tuberculosis Research and Epidemiology
- Pediatric health and respiratory diseases
- Invertebrate Immune Response Mechanisms
- Animal health and immunology
- Parasites and Host Interactions
- Food Allergy and Anaphylaxis Research
- Contact Dermatitis and Allergies
- Drug Transport and Resistance Mechanisms
- Pharmacogenetics and Drug Metabolism
- Fungal Infections and Studies
University of Arizona
2012-2024
Stony Brook University Hospital
2017
Kansas State University
2002
Cryptosporidiosis, caused by the apicomplexan parasite Cryptosporidium parvum, is a diarrheal disease that has produced large global burden in mortality and morbidity humans livestock. There are currently no consistently effective parasite-specific pharmaceuticals available for this disease. Bumped kinase inhibitors (BKIs) specific calcium-dependent protein kinases (CDPKs) have been shown to reduce infection several parasites having medical veterinary importance, including Toxoplasma gondii,...
Bumped kinase inhibitors (BKIs) of Cryptosporidium parvum calcium-dependent protein 1 (CpCDPK1) are leading candidates for treatment cryptosporidiosis-associated diarrhea. Potential cardiotoxicity related to anti-human ether-à-go-go potassium channel (hERG) activity the first-generation anti-Cryptosporidium BKIs triggered further testing efficacy. A luminescence assay adapted high-throughput screening was used measure inhibitory activities against C. in vitro. Furthermore, neonatal and...
There is a substantial need for novel therapeutics to combat the widespread impact caused by Crytosporidium infection. However, there lack of knowledge as which drug pharmacokinetic (PK) characteristics are key generate an in vivo response, specifically whether systemic exposure crucial efficacy. To identify PK properties correlated with efficacy, we generated physiologically based models simulate and gastrointestinal concentrations series bumped kinase inhibitors (BKIs) that have nearly...
Host defence peptides (HDPs) are expressed throughout the animal and plant kingdoms. They have multifunctional roles in against infectious agents of mammals, possessing both bactericidal immune-modulatory activities. We identified a novel family molecules secreted by helminth parasites (helminth molecules; HDMs) that exhibit similar structural biochemical characteristics to HDPs. Here, we analyzed functional activities four HDMs derived from Schistosoma mansoni Fasciola hepatica compared...
Apicomplexan parasites cause severe disease in both humans and their domesticated animals. Since these readily develop drug resistance, development of new, effective drugs to treat infection caused by is an ongoing challenge for the medical veterinary communities. We hypothesized that invertebrate-bacterial symbioses might be a rich source anti-apicomplexan compounds because invertebrates are susceptible infections with gregarines, ancestral all apicomplexans. chose explore therapeutic...
Recent advances in the vitro cultivation of Cryptosporidium parvum using hollow fiber bioreactor technology (HFB) have permitted continuous growth parasites that complete all life cycle stages. The method provides access to stages parasite and a for non-animal production oocysts use clinical trials. Here we examined effect long-term (>20 months) culture on virulence-factors, genome conservation, vivo pathogenicity host by cultured parasites. We find low-level sequence variation is...
The apicomplexan parasite Cryptosporidium parvum is an important cause of diarrhea in humans and cattle, it can persistently infect immunocompromised hosts. No consistently effective parasite-specific pharmaceuticals or immunotherapies for control cryptosporidiosis are presently available. innate immune system represents the first line host defense against a range infectious agents, including parasitic protozoa. Several types antimicrobial peptides proteins, collectively referred to herein...
The protozoan parasite Cryptosporidium sp. is a leading cause of diarrheal disease in those with compromised or underdeveloped immune systems, particularly infants and toddlers resource-poor localities. As an enteric pathogen, invades the apical surface intestinal epithelial cells, where it resides close proximity to metabolites lumen. However, effect gut on susceptibility infection remains largely unstudied. Here, we first identified which are prevalent neonatal mice when they most...
ABSTRACT Cryptosporidium parvum is an important cause of diarrhea in humans and calves can persistently infect immunocompromised hosts. Presently, there are no consistently effective parasite-specific drugs for cryptosporidiosis. We hypothesized that neutralizing monoclonal antibodies (MAbs) targeting the apical complex surface antigens CSL, GP25-200, P23 could passively immunize against recently reported a formulation MAbs 3E2 (anti-CSL), 3H2 (anti-GP25-200), 1E10 (anti-P23) provided...
The coccidian parasite Cryptosporidium parvum causes diarrhea in humans, calves, and other mammals. Neither immunization nor parasite-specific pharmaceuticals that are consistently effective against this organism available. While polyclonal antibodies whole C. reduce infection, their efficacy predictability suboptimal. We hypothesized passive cryptosporidiosis could be improved by using neutralizing monoclonal (MAbs) targeting functionally defined antigens on the infective stages. previously...
Cryptosporidium parvum calcium-dependent protein kinase 1 (CpCDPK1) is a promising target for drug development against cryptosporidiosis. We report series of low-nanomolar CpCDPK1 5-aminopyrazole-4-carboxamide (AC) scaffold inhibitors that also potently inhibit C. growth in vitro Correlation between anti-CpCDPK1 and inhibition, as previously reported pyrazolopyrimidines, was not apparent. Nonetheless, lead AC compounds exhibited substantial reduction parasite burden the neonatal mouse...
Infection with Cryptosporidium spp. can cause severe diarrhea, leading to long-term adverse impacts and even death in malnourished children immunocompromised patients. The only FDA-approved drug for treating cryptosporidiosis, nitazoxanide, has limited efficacy the populations impacted most by diarrheal disease, safe, effective treatment options are urgently needed.
ABSTRACT The protozoan parasite Cryptosporidium parvum is a leading cause of diarrhea in humans and neonatal calves. absence approved parasite-specific drugs, vaccines, immunotherapies for cryptosporidiosis relates part to limited knowledge on the pathogenesis zoite attachment invasion. We recently reported that C. apical complex glycoprotein CSL contains ligand intestinal epithelial cells which defined by monoclonal antibody (MAb) 3E2. In present study, host cell receptor was characterized....
ABSTRACT At present no completely effective treatments are available for Cryptosporidium parvum infections in humans and livestock. Based on previous data showing the neutralizing potential of a panel monoclonal antibodies developed against C. , based fact that innate immune peptides enzymes have anticryptosporidial activity, we engineered several these into antibody-biocide fusion proteins. We hypothesized combination high-affinity antibody targeting with molecule-mediated killing would...
The objective of this study was to determine whether changes in the ileal intraepithelial lymphocyte (TEL) phenotype and function occurred prior development diarrhea Cryptosporidium parvum-infected calves. Calves were orally inoculated with 10(8) oocysts maintained enteric pathogen-free conditions until their use experiments. Age-matched uninfected calves used for comparisons. Ileal IELs isolated phenotyped population dynamics had by 3 days postinoculation (PI). Ex vivo reverse...
Recent advances on the development of bumped kinase inhibitors for treatment cryptosporidiosis have focused 5-aminopyrazole-4-carboxamide scaffold, due to analogs that less hERG inhibition, superior efficacy, and strong in vitro safety profiles. Three compounds, BKI-1770, -1841, -1708, showed efficacy C. parvum infected mice. Both BKI-1770 BKI-1841 had newborn calf model, reducing diarrhea oocyst excretion. However, both compounds caused hyperflexion limbs seen as dropped pasterns. Toxicity...