Penn Vet researchers developed the Cryptosporidium single-cell atlas, revealing which genes are expressed at which points across the parasite’s life cycle. On the left, the atlas shows parasites replicating asexually in green, with males in blue and females in pink. On the right, micrographs of the stages are shown, with their nuclei highlighted in green. (Image: Boris Striepen)
There are currently no effective drugs or vaccines to prevent or treat cryptosporidiosis, a potentially deadly waterborne diarrheal disease that is a leading cause of child mortality around the world. In this disease, the Cryptosporidium parasite infects the cells that line the intestines and engages in both asexual and sexual replication, which researchers suspect are both critical to sustained infection and transmission. These parasites do not have sex chromosomes, and the mechanism by which they become male or female is unknown. Revealing how they choose a sex provides a potential target to block transmission and infection.
A new study from the lab of Boris Striepen, PhD, published in Nature, defines the molecular components of all life cycle stages to reveal the underlying mechanisms and demonstrates that the sexual part of the lifecycle is critical to infection and that blocking it will block the infection.
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The microscopy image shows seminoma tissue in patient’s testis showing large, round cells with clear cytoplasm. The tumor tissue is heavily infiltrated by lymphocytes (small cells with dark/blue nuclei). (Image: Kotaro Sasaki)
Seminoma, a type of testicular cancer that predominantly affects young men, is the most common testicular germ cell tumor. Despite a generally favorable prognosis with high cure rates through chemotherapy, approximately 10% of seminoma cases exhibit resistance, leading to metastasis and challenging relapses.
In a paper published in the journal Cell Reports, a team led by Kotaro Sasaki, MD, PhD, and collaborators developed the first in vitro seminoma model and presented the most comprehensive single-cell atlas of human male germ cell development reported to date, shedding light on chromosomal anomalies and signaling pathways that may contribute to seminoma development.
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Bonnie Vecchiarelli, second from left; Dipti Pitta, middle; and Nagaraju Indugu, right, are among the authors on a new paper examining the mechanisms by which a type of red seaweed inhibits methane emissions from dairy cows, with John Toth and Rachel Duffey, also of the University of Pennsylvania School of Veterinary Medicine. (Image: Dipti Pitta)
Methane emissions from livestock are a major constituent of the greenhouse gases currently driving global warming. As part of an effort to address climate change, a collaborative study by Penn Vet’s Dipti Pitta, MVSc, PhD; Nagaraju Indugu, PhD; and colleagues looked at how adding a red seaweed, Asparagopsis taxiformis (AT), to the diet of dairy cattle reduces methane emissions. The results, published in mBio, showed that a high dose of the seaweed initially inhibited methane emissions by 55%, but the effect gradually declined over time. These findings provide insight into AT-driven reduction in methane emissions and illuminate additional pathways that may need to be targeted to maintain its inhibitory effects while preserving microbiome health and animal productivity.
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A lot of research progress has been over the past decade on Cryptosporidium, a single-celled parasite that is one of the leading causes of deadly diarrheal disease, and Penn Vet professors brought together researchers and clinicians from around the world for a conference. (Image: Muthgapatti Kandasamy and Boris Striepen)
A Hopeful Time for Cryptosporidium Research
Ten percent of child mortality worldwide comes from diarrheal disease, and after rotavirus, Cryptosporidium is the main cause. With support from the Bill & Melinda Gates Foundation and the National Institutes of Health, Boris Striepen, PhD, and others have pursued an ambitious research agenda. Genetic engineering of the parasite, along with new culture and animal models, have enabled progress toward drugs and vaccines. For the first time in many years, new candidate drugs have now entered human trials.
Dr. Striepen and Christopher A. Hunter, PhD, also of Penn Vet, sought to amplify these advances by organizing the First Biennial Cryptosporidium Meeting, which was held at Penn Vet. The event included academic researchers from across disciplines, scientists from leading pharmaceutical companies, representatives of United States and international public health agencies, and leading clinicians from some of the most impacted countries, including Zambia, Kenya, Colombia, Bangladesh, and India. The meeting received comprehensive coverage in Cell Press
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A game warden with the Pennsylvania Game Commission holds a wild turkey during a turkey trapping in northeastern Pennsylvania. Also in attendance were people from Penn Vet's Wildlife Futures Program: Lauren Maxwell, wildlife health technician, and R. Scott Larsen, wildlife veterinary liaison. (Image: R. Scott Larsen/Wildlife Futures Program)
Understanding Disease Prevalence in Pennsylvania Wild Turkeys
Lymphoproliferative disease virus (LPDV) is a retrovirus that affects wild turkeys. The virus results in organ tumors, skin tumors, and sometimes cancer. To learn more about its prevalence in Pennsylvania wild turkeys, population-level impacts, and potential co-infection with other diseases, Erick Gagne, PhD, and Eman A. Anis, PhD, of Penn Vet’s Wildlife Futures Program, are leading the Wild Turkey Health Project, Penn’s contribution to a larger, multi-year turkey monitoring study in collaboration with Penn State and the Pennsylvania Game Commission.
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(Image: Adobe Stock)
Uncovering the Neural Pathways for Primate Reciprocity, Social Support, and Empathy
Social interaction is key to survival and reproductive success in primates, including humans. Optimizing outcomes from these encounters requires a calculated approach to cooperation and competition—knowing whom to trust, whom to avoid, or whom to confront confers an evolutionary advantage.
Kristin Gardiner, VMD, was a contributing author and co-surgeon on a study, published in Nature, that combined neuroscience and ethology in primates and uncovered neural signatures of social support and grooming reciprocity, which are the building blocks of primate relationships. The project was led by Dr. Michael L. Platt, a neuroscientist at the Perelman School of Medicine.
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A mutation in the NPHP5 gene leads to a severe blinding disorder, Leber congenital amaurosis. Dogs with the condition that were treated with a gene therapy regrew normal, functional cone cells, labeled in red, that had previously failed to develop. The treatment led to a recovery of retinal function and vision.
Strong Representation at the Annual Meeting of the Association for Research in Vision and Ophthalmology
Penn Vet’s Division of Experimental Retinal Therapies (ExpeRTs), led by Gustavo D. Aguirre, VMD, PhD, and William A. Beltran, DVM, PhD, was well represented at this year’s Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), held in Seattle, Washington, May 5—9, 2024. Nine abstracts were presented by the ExpeRTs.
Clinical characterization of canine cone-rod dystrophy with early foveo-macular degeneration.
G.D. Aguirre, V.L. Dufour, L. Murgiano, J.C. Kwok, W.A. Beltran.
Adaptive glial cell and gene expression alterations in retinas of treated and untreated RPE65 mutant dogs.
T. Appelbaum, E. Santana, D. Smith, W.A. Beltran, G.D. Aguirre.
Development of OPGx-BEST1 AAV gene therapy for the treatment of bestrophinopathies.
M. Choudhary, A. Gray, Y. Sato, J.C. Kwok, V. Arora, B.R. Yerxa, A.V. Cideciyan, G.D. Aguirre, W.A. Beltran, A. Jayagopal.
A canine model for ABCA4 Stargardt disease: in-vivo phenotypic characterization and natural disease history.
V.L. Dufour, A.V. Cideciyan, J. Kwok, A. Gray, Y. Sato, K. Quigley, W.A. Beltran, G.D. Aguirre.
Assessment of the Orbit™ Subretinal Delivery System (OSDS™) and prototypes in adult and juvenile canine eyes.
J.C. Kwok, A. Gray, Y. Sato, S. Reichenbacker, T. Meyer, K. Stoner, W.A. Beltran.
Frameshift variant in the Cirneco dell’Etna dog with syndromic retinopathy and tremors.
L. Murgiano, J.K. Niggel, L. Benedicenti, A. Bionda, M. Cortellari, P. Crepaldi, G.K. Aguirre, W.A. Beltran, G.D. Aguirre.
DNA extraction and amplification from osmicated EPONbedded retinal and corneal tissues.
J. Niggel, G. Aguirre, L. Murgiano.
Identification of photoreceptor-specific promoters for gene therapy at advanced stages of retinal degeneration.
R. Sudharsan, L. Murgiano, A. Ahuja, Y. Sato, J.C. Kwok, M. Sedorovitz, G.D. Aguirre, L. Byrne, W.A. Beltran.
Ultrastructure expansion microscopy for characterization of the canine photoreceptor sensory cilium.
K. Takahashi, R. Sudharsan, W.A. Beltran.
Left to right: Michael Hogan, Daniela Luethy, Louise Moncla, Wojciech Panek, and Antonella Rotolo
Frontier Explorers: Penn Vet Scientists on the Cutting Edge
From trailblazing targeted cancer therapies to racing pigeons, understanding dementia to singing arias, five of Penn Vet’s newest faculty share their personal passions and what ignites their pursuit of “what’s next” in the profession. Get to know Michael J. Hogan, PhD; Daniela Luethy, MPH, DVM, DACVIM; Louise H. Moncla, PhD; Wojciech K. Panek, DVM, DACVIM; and Antonella Rotolo, MD, PhD, in this feature article from the latest issue of Bellwether.
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