In-Depth Genetic Analyses to Identify New Targets for Malaria Vaccines and Therapies

Technology Overview

Dr. Ashley Vaughan

Malaria kills more than 600,000 people a year, mostly children. Resistance to antimalarial drugs is widespread in Asia and increasing in Africa. In addition, effective malaria prevention requires improved vaccines against the Plasmodium parasites that cause the disease.

Ashley Vaughan, PhD, is an expert in Plasmodium genetics and biology who develops and tests vaccines based on genetically attenuated parasites. He also investigates poorly understood aspects of the complex Plasmodium life cycle to discover markers of drug resistance and to identify genes, proteins and cellular processes to target with new vaccines and therapeutics.

Many groundbreaking studies on the liver stages of the human malaria parasites, Plasmodium falciparum and Plasmodium vivax, use chimeric animal models with human liver cells that were pioneered by Dr. Vaughan in collaboration with Seattle Children’s researchers Sebastian Mikolajczak, PhD, and Stefan Kappe, PhD. Additionally, Dr. Vaughan established a method for using these chimeric animal models for genetic crosses of P. falciparum that has helped reveal genes and combinations of genes involved in drug resistance and parasite fitness.

As one example, Dr. Vaughan and collaborators used genetic crosses, along with population genomics analyses and CRISPR gene editing of parasites, to show that a putative amino acid transporter contributes to drug resistance to chloroquine, an antimalarial drug.

New vaccine and drug targets from parasite liver-stage studies

Dr. Vaughan’s animal models with humanized livers are a foundational advance that facilitates studies on a critical stage of the Plasmodium life cycle: maturation and growth in the liver before the parasite transitions to the host’s blood. The parasitic liver stage is understudied, and knowledge about this stage is essential to preventing and treating malaria. Ongoing studies by Dr. Vaughan and colleagues include:

• Analysis of the dormant, hypnozoite liver stage of P. vivax. The quiescent hypnozoite liver stage of P. vivax is difficult to eliminate and only two drugs are available for parasite clearance. Reactivation of the parasites results in malaria relapse that can occur years after the initial infection. Differential gene expression analysis by Dr. Vaughan and colleagues has identified P. vivax RNA-binding proteins with vaccine and therapeutic potential because these key proteins control parasite dormancy and potentially reactivation.
• Genome-wide transcriptomics. Dr. Vaughan and collaborators have reported the full developmental transcriptome of the liver-stage P. falciparum. This gene expression information is particularly valuable for future vaccine developments and prophylactic drug development.
• Characterization of monoclonal antibodies against liver-stage parasites. The Vaughan Lab collaborated on a study of 10 antibodies that originated from P. falciparum-exposed individuals. The antibodies bind sporozoite-stage parasites that infect the liver. Evidence from the study supports the antibodies as candidates for novel therapeutics and suggest the antibody-binding site is a potential antigen for new malaria vaccines.
• Analysis of mutations in the pathway for Plasmodium protein glycosylation. Dr. Vaughan and colleagues have used gene-edited Plasmodium to demonstrate that disrupting this process can prevent parasites from colonizing mosquito salivary glands and infecting human liver cells.

Dr. Vaughan has experience working with industry collaborators, including on Plasmodium genes involved in drug resistance and on clinical trials for malaria vaccines using genetically attenuated parasites that enter the liver but cannot replicate. Dr. Vaughan is interested in partnerships to develop and test vaccines, monitor and reduce drug resistance, and screen new antimalarial drugs.

Stage of Development

• Preclinical in vitro
• Preclinical in vivo
• Clinical trials

Partnering Opportunities

• Collaborative research opportunity
• Sponsored research agreement
• Licensing agreement
• Consultation agreement
• Medium-throughput drug and drug-resistance screening

Learn More

• Ashley Vaughan, PhD
• Vaughan Lab

Publications

1. Gupta P, Rezakhani N, Pazzagli L … Vaughan AM, et al. Glycosylation of Plasmodium falciparum TRAP supports sporozoite motility and invasion. bioRxiv [Preprint]. 2025:2025.06.26.658380.
2. Zanghí G, Patel H, Smith JL … Vaughan AM, et al. Genome-wide gene expression profiles throughout human malaria parasite liver stage development in humanized mice. Nat Microbiol. 2025;10(2):569-584.
3. Dacon C, Moskovitz R, Swearingen K … Vaughan A, et al. Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein. Science. 2025;387(6729):eadr0510.
4. Vo KC, van Biljon R, Zanghi G … Vaughan AM, et al. Two Plasmodium vivax hypnozoite-expressed RNA-binding proteins inhibit liver stage replication. Nat Commun. 2026;17:7048.
5. Amambua-Ngwa A, Button-Simons KA, Li X… Vaughan AM, et al. Chloroquine resistance evolution in Plasmodium falciparum is mediated by the putative amino acid transporter AAT1. Nat Microbiol. 2023;8(7):1213-1226.
6. Goswami D, Betz W, Locham NK … Vaughan AM, et al. A replication-competent late liver stage-attenuated human malaria parasite. JCI Insight. 2020;5(13):e135589.

Last updated August 2026