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Tag: Jessica Kissinger

Analysis of Long Non-Coding RNA in Cryptosporidium parvum Reveals Significant Stage-Specific Antisense Transcription

Cryptosporidium is a protist parasite that has been identified as the second leading cause of moderate to severe diarrhea in children younger than two and a significant cause of mortality worldwide. Cryptosporidium has a complex, obligate, intracellular but extra cytoplasmic lifecycle in a single host. How genes are regulated in this parasite remains largely unknown. Long non-coding RNAs (lncRNAs) play critical regulatory roles, including gene expression across a broad range of organisms. Cryptosporidium lncRNAs have been reported to enter the host cell nucleus and affect the host response. However, no systematic study of lncRNAs in Cryptosporidium has been conducted to identify additional lncRNAs. In this study, we analyzed a C. parvum in vitro strand-specific RNA-seq developmental time series covering both asexual and sexual stages to identify lncRNAs associated with parasite development. In total, we identified 396 novel lncRNAs, mostly antisense, with 86% being differentially expressed. Surprisingly, nearly 10% of annotated mRNAs have an antisense transcript. lncRNAs occur most often at the 3′ end of their corresponding sense mRNA. Putative lncRNA regulatory regions were identified and many appear to encode bidirectional promoters. A positive correlation between lncRNA and upstream mRNA expression was observed. Evolutionary conservation and expression of lncRNA candidates was observed between C. parvumC. hominis and C. baileyi. Ten C. parvum protein-encoding genes with antisense transcripts have P. falciparum orthologs that also have antisense transcripts. Three C. parvum lncRNAs with exceptional properties (e.g., intron splicing) were experimentally validated using RT-PCR and RT-qPCR. This initial characterization of the C. parvum non-coding transcriptome facilitates further investigations into the roles of lncRNAs in parasite development and host-pathogen interactions.

Yiran Li, Rodrigo P. Baptista, Adam Sateriale, Boris Striepen and Jessica C. Kissinger. Front Cell Infect Microbiol. 2021 Jan 14;10:608298. doi: 10.3389/fcimb.2020.608298. eCollection 2020.

Jessica Kissinger elected ASTMH Fellow

Jessica Kissinger
Jessica Kissinger (Photo by Peter Frey)

University of Georgia geneticist Jessica Kissinger has been elected a 2020 American Society of Tropical Medicine and Hygiene Fellow.

Kissinger is a Distinguished Research Professor in the Department of Genetics, part of the Franklin College of Arts and Sciences. She also holds appointments in the Institute of Bioinformatics and Center for Tropical and Emerging Global Diseases.

“I value belonging to a society that is focused on global health and lessening the burden of tropical infectious diseases, and I am truly honored to be recognized as a Fellow at a time when a focus on public health, science and climate change is so important for all of us,” said Kissinger.

Kissinger’s research focuses on parasite genomics and the biology of genome evolution. Her research group is trying to answer big questions such as how genomes evolve, what is the fate of horizontally transferred genes, which genes are phylogenetically restricted, and how do organellar genomes evolve? The answers to these questions will increase the understanding of parasite biology and help researchers identify potential drug and vaccine targets.

Kissinger’s research mainly focuses on Apicomplexan parasites, a group of parasites that include species that cause malaria, toxoplasmosis and cryptosporidiosis. Projects in her laboratory include the development of tools for data integration, data mining, comparative genomics and assessing the phylogenetic distribution of genes. Her research group oversees integrated genomic database resources, which are part of the Eukaryotic Pathogen, Vector and Host Informatics Resources (, funded by the National Institutes of Health. This resource provides the international research community with open access to data for many pathogenic and related organisms.

Kissinger’s research has been funded by the NIH, the Bill and Melinda Gates Foundation, the Defense Advanced Research Projects Agency, the Wellcome Trust, the United States Department of Agriculture, and the National Science Foundation. Notably, she is the joint principal investigator of a $38.4 million (if all options are exercised) NIH contract that supports VEupathDB.

Kissinger joined the faculty of UGA in 2001. She was a founding member of the Institute of Bioinformatics at UGA to facilitate cutting-edge interdisciplinary research in bioinformatics/computational biology and its applications. Kissinger has been recognized many times for research and leadership. She has been awarded a Creative Research Medal, Faculty Excellence in Diversity Leadership Award and the Richard F. Reiff Internationalization Award from UGA. In 2014, she was awarded a Special Visiting Professorship from Brazil’s national science research agency, and most recently, she was awarded a Fulbright U.S. Scholar award to teach and conduct research at Makerere University in Uganda.

“Being elected as a Fellow of the American Society of Tropical Medicine and Hygiene is recognition of a scientist that has made significant contributions to global public health,” said Dennis Kyle, director of the Center for Tropical and Emerging Global Diseases. “Dr. Kissinger richly deserves this award, and I look forward to her continued leadership in tropical medicine research.”

Resistance to some, but not other dimeric lindenane sesquiterpenoid esters is mediated by mutations in a Plasmodium falciparum esterase

Unique lindenane sesquiterpenoid dimers from Chloranthecae spp. were recently identified with promising in vitro antiplasmodial activity and potentially novel mechanisms of action. To gain mechanistic insights to this new class of natural products, in vitro selection of Plasmodium falciparum resistance to the most active antiplasmodial compound, chlorajaponilide C, was explored. In all selected resistant clones, the half-maximal effective concentration (EC50) of chlorajaponilide C increased >250-fold, and whole genome sequencing revealed mutations in the recently discovered P. falciparum prodrug activation and resistance esterase (PfPARE). Chlorajaponilide C was highly potent (mean EC50 = 1.6 nM, n=34) against fresh Ugandan P. falciparum isolates. Analysis of the structure-resistance relationships revealed that in vitro potency of a subset of lindenane sesquiterpenoid dimers was not mediated by PfPARE mutations. Thus, chlorajaponilide C, but not some related compounds, required parasite esterase activity for in vitro potency, and those compounds serve as the foundation for development of potent and selective antimalarials.

Joshua H Butler, Rodrigo P Baptista, Ana Lisa Valenciano, Bin Zhou, Jessica C Kissinger, Patrick K Tumwebaze, Philip J Rosenthal, Roland Cooper, Jian-Min Yue, Maria Belen Cassera. ACS Infect Dis. 2020 Sep 24. doi: 10.1021/acsinfecdis.0c00487

Noncoding RNAs in Apicomplexan Parasites: An Update

Illustration of Long Noncoding RNA (lncRNA) Functions in Apicomplexan Parasites.

Recent breakthroughs in high-throughput technologies, transcriptomics, and advances in our understanding of gene regulatory networks have enhanced our perspective on the complex interplay between parasite and host. Noncoding RNA molecules have been implicated in critical roles covering a broad range of biological processes in the Apicomplexa. Processes that are affected range from parasite development to host–parasite interactions and include interactions with epigenetic machinery and other regulatory factors. Here we review recent progress involving noncoding RNAs and their functions in the Apicomplexa, with a focus on three parasites: PlasmodiumToxoplasma, and Cryptosporidium. We discuss the limitations and challenges of current methods applied to apicomplexan noncoding RNA study and discuss future directions in this exciting field.




Yiran Li, Rodrigo P. Baptista, Jessica C. Kissinger. Trends Parasitol. 2020 Aug 19;S1471-4922(20)30189-6.

Update on Cryptosporidium spp.: highlights from the Seventh International Giardia and Cryptosporidium Conference

While cryptosporidiosis is recognized as being among the most common causes of human parasitic diarrhea in the world, there is currently limited knowledge on Cryptosporidium infection mechanisms, incomplete codification of diagnostic methods, and a need for additional therapeutic options. In response, the Seventh International Giardia and Cryptosporidium Conference (IGCC 2019) was hosted from 23 to 26 June 2019, at the Rouen Normandy University, France. This trusted event brought together an international delegation of researchers to synthesize recent advances and identify key research questions and knowledge gaps. The program of the interdisciplinary conference included all aspects of host-parasite relationships from basic research to applications to human and veterinary medicine, and environmental issues associated with waterborne parasites and their epidemiological consequences. In relation to Cryptosporidium and cryptosporidiosis, the primary research areas for which novel findings and the most impressive communications were presented and discussed included: Cryptosporidium in environmental waters, seafood, and fresh produce; Animal epidemiology; Human cryptosporidiosis and epidemiology; Genomes and genomic evolution encompassing: Comparative genomics of Cryptosporidium spp., Genomic insights into biology, Acquiring and utilizing genome sequences, Genetic manipulation; Host-parasite interaction (immunology, microbiome); and Diagnosis and treatment. High quality presentations discussed at the conference reflected decisive progress and identified new opportunities that will engage investigators and funding agencies to spur future research in a “one health” approach to improve basic knowledge and the clinical and public health management of zoonotic cryptosporidiosis.

Giovanni Widmer, David Carmena, Martin Kváč, Rachel M. Chalmers, Jessica C. Kissinger, Lihua Xiao, Adam Sateriale, Boris Striepen, Fabrice Laurent, Sonia Lacroix-Lamandé, Gilles Gargala and Loïc Favennec. Parasite. 2020;27:14. doi: 10.1051/parasite/2020011.

Sharing the Knowledge: NIH Award Supports Expanded Genomics Data Resource

By: Alan Flurry

A team led by scientists at the University of Pennsylvania and University of Georgia provides thousands of researchers around the world with access to the Eukaryotic Pathogen Genomics Database (, a collection of resources for analyzing large-scale datasets associated with microbial pathogens. These include the parasites responsible for malaria, sleeping sickness, and toxoplasmosis; the fungi responsible for thrush, aspergillosis and Valley Fever; and many other important diseases. In parallel, a team led by investigators at the University of Notre Dame has been responsible for similar resources covering invertebrate vectors of disease (, including the mosquitoes transmitting malaria, Zika, and yellow fever, the ticks responsible for Lyme disease and Rocky Mountain Spotted Fever, and others.

To ensure that this important work continues, the National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health, has awarded a new contract to integrate these resources, worth up to $7.2 million in 2019-2020. The five‐year award for this project, rebranded as (The Eukaryotic Pathogen, Host & Vector Genomics Resource) could total as much as $38.4 million if all associated options are exercised.

The patterns revealed by such “Big Data” provide insight into important diseases, permit the development of diagnostic methods, and define drug and vaccine targets. But to be useful, these immense datasets must be sensibly organized and made conveniently accessible to the researchers worldwide. The integrated VEuPathDB database hosts data on thousands of genomes, representing hundreds of species, along with extensive information on isolate provenance, gene function and the like.

The award is based at Penn, and directed by David S Roos, E Otis Kendall Professor of Biology in the School of Arts & Sciences. Key subcontracts include the University of Georgia (Joint PI Jessica C. Kissinger, Distinguished Professor of Genetics and Bioinformatics in the Franklin College of Arts and Sciences and the Center for Tropical and Emerging Global Diseases), University of Notre Dame (Joint PI Mary Ann McDowell, Associate Professor of Biological Sciences at the Eck Institute for Global Health).  Additional co-investigators include Professors Christian Stoeckert of Penn’s Perelman School of Medicine, Mark Caddick of the University of Liverpool, George K Christophides of Imperial College London, and Paul Flicek, Associate Director of the EMBL-EBI (European Bioinformatics Institute).

“It is wonderful to see the continued investment by NIH, the Wellcome Trust and others in resources that make performing much needed global research on infectious diseases both easier and better,” Kissinger said. “Datasets are larger and more complex than ever due to significant advances in technology. These breakthroughs create challenges for making the resulting data truly accessible and usable by the average researcher.  We strive to remove barriers, integrate diverse data and accelerate the speed with which new hypotheses can be generated and ideas tested both in silico and in the lab.”

“A critical aspect of this now joint program will be its accessibility throughout the world, empowering any infectious disease investigator to interrogate these highly complex databases in comprehensible and productive ways,” said Dan Colley, UGA professor of microbiology and member of the CTEGD who has conducted extensive research on n schistosomiasis in western Kenya. “These databases have led, and the merged data base will lead, to the design of new drugs and studies on how to better control and eliminate these major public health challenges, such as malaria, toxoplasmosis, yellow fever, eastern equine encephalitis and Lyme disease.”

“Since its conception, corresponding with the release of the first parasite genomes, EuPathDB has been a transformative tool in our search for a better understanding of human disease and parasite biology,” said Stephen Hadjuk, Professor Emeritus of biochemistry & molecular biology at UGA whose lab investigates trypanosomes, the causative agent of an human African sleeping sickness. “Today, it’s difficult to imagine any serious research on parasites and host pathology that doesn’t rely, at least to some extent, on EuPathDB. The decision to incorporate the vectors database into the eukaryotic pathogens database was brilliant, and makes this is an exciting new chapter in the EuPathDB story.”

“Innumerable investigators, including my own laboratory, rely on daily access to the high quality genomic and functional datasets made available by the VEuPathDB Project,” says Keith Gull, Professor of Molecular Microbiology at Oxford University.  “Sustainable support for such resources is imperative if we are to capitalize on the promise of modern technologies for scientific discovery and translational application.”  Joe Heitman, James B Duke Professor / Chair of Molecular Genetics & Microbiology at Duke University agrees: “Inclusion of fungal pathogens under the BRC umbrella has greatly enhanced our ability to study important human mycoses.  Cross-species comparisons provide insights into the biology and pathogenesis of these fascinating organisms, which can be deadly – but can also serve as workhorses for valuable biotechnology development.”

Originally published at

Clinically silent relapsing malaria may still pose a threat

The immune system can control a relapsing form of malaria enough to avoid clinical signs of disease, but it doesn’t eliminate transmissible parasites from the body that may still be infectious to mosquitoes. That’s the conclusion of a study on a nonhuman primate model of Plasmodium vivax infection, which has implications relevant to malaria elimination strategies.

Keep reading about the MaPHIC study at

Accessing Cryptosporidium Omic and Isolate Data via

Cryptosporidium has historically been a difficult organism to work with, and molecular genomic data for this important pathogen have typically lagged behind other prominent protist pathogens. CryptoDB ( ) was launched in 2004 following the appearance of draft genome sequences for both C. parvum and C. hominis. CryptoDB merged with the EuPathDB Bioinformatics Resource Center family of databases ( ) and has been maintained and updated regularly since its establishment. These resources are freely available, are web-based, and permit users to analyze their own sequence data in the context of reference genome sequences in our user workspaces. Advances in technology have greatly facilitated Cryptosporidium research in the last several years greatly enhancing and extending the data and types of data available for this genus. Currently, 13 genome sequences are available for 9 species of Cryptosporidium as well as the distantly related Gregarina niphandrodes and two free-living alveolate outgroups of the Apicomplexa, Chromera velia and Vitrella brassicaformis. Recent years have seen several new genome sequences for both existing and new Cryptosporidium species as well as transcriptomics, proteomics, SNP, and isolate population surveys. This chapter introduces the extensive data mining and visualization capabilities of the EuPathDB software platform and introduces the data types and tools that are currently available for Cryptosporidium. Key features are demonstrated with Cryptosporidium-relevant examples and explanations.

Warrenfeltz S, Kissinger JC, EuPathDB Team. Methods Mol Biol. 2020;2052:139-192. doi: 10.1007/978-1-4939-9748-0_10.

A Genetically Tractable, Natural Mouse Model of Cryptosporidiosis Offers Insights into Host Protective Immunity

Cryptosporidium is a leading cause of diarrheal disease and an important contributor to early childhood mortality, malnutrition, and growth faltering. Older children in high endemicity regions appear resistant to infection, while previously unexposed adults remain susceptible. Experimental studies in humans and animals support the development of disease resistance, but we do not understand the mechanisms that underlie protective immunity to Cryptosporidium. Here, we derive an in vivo model of Cryptosporidium infection in immunocompetent C57BL/6 mice by isolating parasites from naturally infected wild mice. Similar to human cryptosporidiosis, this infection causes intestinal pathology, and interferon-γ controls early infection while T cells are critical for clearance. Importantly, mice that controlled a live infection were resistant to secondary challenge and vaccination with attenuated parasites provided protection equal to live infection. Both parasite and host are genetically tractable and this in vivo model will facilitate mechanistic investigation and rational vaccine design.

Adam Sateriale, Jan Šlapeta, Rodrigo Baptista, Julie B. Engiles, Jodi A. Gullicksrud, Gillian T. Herbert, Carrie F. Brooks, Emily M. Kugler, Jessica C. Kissinger, Christopher A. Hunter, Boris Striepen. Cell Host Microbe. 2019 Jun 18. pii: S1931-3128 (19) 30251-3. doi: 10.1016/j.chom.2019.05.006.

Distinct amino acid and lipid perturbations characterize acute versus chronic malaria

Chronic malaria is a major public health problem and significant challenge for disease eradication efforts. Despite its importance, the biological factors underpinning chronic malaria are not fully understood. Recent studies have shown that host metabolic state can influence malaria pathogenesis and transmission, but its role in chronicity is not known. Here, with the goal of identifying distinct modifications in the metabolite profiles of acute versus chronic malaria, metabolomics was performed on plasma from Plasmodium-infected humans and nonhuman primates with a range of parasitemias and clinical signs. In rhesus macaques infected with Plasmodium coatneyi, significant alterations in amines, carnitines, and lipids were detected during a high parasitemic acute phase and many of these reverted to baseline levels once a low parasitemic chronic phase was established. Plasmodium gene expression, studied in parallel in the macaques, revealed transcriptional changes in amine, fatty acid, lipid and energy metabolism genes, as well as variant antigen genes. Furthermore, a common set of amines, carnitines, and lipids distinguished acute from chronic malaria in plasma from human Plasmodium falciparum cases. In summary, distinct host-parasite metabolic environments have been uncovered that characterize acute versus chronic malaria, providing insights into the underlying host-parasite biology of malaria disease progression.

Regina Joice Cordy, Rapatbhorn Patrapuvich, Loukia N. Lili, Monica Cabrera-Mora, Jung-Ting Chien, Gregory K. Tharp, Manoj Khadka, Esmeralda V.S. Meyer, Stacey A. Lapp, Chester J. Joyner, AnaPatricia Garcia, Sophia Banton, ViLinh Tran, Viravarn Luvira, Siriwan Rungin, Teerawat Saeseu, Nattawan Rachaphaew, Suman B. Pakala, Jeremy D. DeBarry, MaHPIC Consortium, Jessica C. Kissinger, Eric A. Ortlund, Steven E. Bosinger, John W. Barnwell, Dean P. Jones, Karan Uppal, Shuzhao Li, Jetsumon Sattabongkot, Alberto Moreno, and Mary R. Galinski. 2019. JCI Insight.; 4(9). pii: 125156. doi: 10.1172/jci.insight.125156.