Research

My research is broadly focused on vector-borne disease biology. I use ecological and evolutionary approaches to better understand pathogen biology that has direct impacts on human and animal health. My research is grounded in a One Health approach, meaning that the health of wildlife, companion animals, livestock, humans, and ecosystems are all interwoven and can only be fully understood in combination.

Vector-borne pathogens have highly complex biology, involving unique adaptations to at least two different hosts. These pathogens must adapt to arthropod-borne transmission, as well as reproduction within a vertebrate host. This unique biology incorporates adaptations to arthropod behavior and immunity as well as vertebrate behavior and immunity. My research focuses on understanding the behavioral, ecological, evolutionary, and genomic foundations of mosquito-transmitted pathogens, particularly malaria and other eukaryotic parasites.

Mosquito and Pathogen Molecular Ecology

Connecticut is home to numerous competent mosquito vectors of diseases, including three zoonotic viruses (Eastern Equine Encephalitis Virus, Jamestown Canyon Virus, and West Nile Virus) and two types of enzootic eukaryotic pathogens, avian malaria (Plasmodium spp., Haemoproteus spp., Leucocytozoon spp.) and heartworm (Dirofilaria spp.).

I am interested in the molecular ecology and epidemiology of these pathogens and their vectors in Western Connecticut. This work has a large field component, incorporating mosquito trapping at the Westside Nature Preserve. In the future, I hope to also incorporate vertebrate blood sampling and am eager to collaborate with veterinarians and/or wildlife biologists on this project.

The laboratory component of this research involves morphological identification, followed by a mix of molecular approaches to identify pathogens, blood meal sources, and nectar sources: PCR, metagenomics, and amplicon sequencing. The computational component of this research involves bioinformatic techniques to accomplish the above goals, as well as analyses to uncover the molecular ecology and genomic epidemiology of mosquito-borne pathogens in Western Connecticut.

Malaria Genomics

I have an ongoing research collaboration with the Infectious Disease Epidemiology and Ecology Lab (IDEEL) at UNC and the Bailey Lab at Brown. Six malaria species regularly infect humans, with Plasmodium falciparum causing the highest morbidity and mortality worldwide, particularly in sub-Saharan Africa. While the other five species tend to cause less severe and less dense infections than P. falciparum, they can still lead to serious complications, frequently occur in mixed-species infections with P. falciparum, and may increase in prevalence as P. falciparum is controlled and eventually eliminated.

My research focuses on the genomic epidemiology and population genomics of these non-falciparum malarias (with the exception so far of P. knowlesi). This research is driven by four major questions:

1. What are the mosquito vectors of P. malariae, P. ovale spp., and P. vivax in Africa?
2. How are African Plasmodium populations related to each other and populations from elsewhere?
3. How will non-falciparum Plasmodium populations change in response to intensive P. falciparum control?
4. How will non-falciparum Plasmodium populations change in response to global climate change and the spread of non-native species, such as Anopheles stephensi?

Plasmodium malariae

P. malariae is a neglected malaria species that can cause severe clinical manifestations and long-term persistent infections, but its biology is poorly understood. I led the most thorough population genomics analysis of this neglected pathogen to-date, in collaboration with researchers at UNC, Brown, MRC Unit The Gambia, the National Institute for Medical Research (Tanzania), Kinshasa School of Public Health, Muhimbili University of Health and Allied Sciences, University of Dschang, and Programme nationale de lutte contre le paludisme (DRC). We found no evidence of geographic population structure, evidence of recovery from a genetic bottleneck, and signatures of selective sweep on antimalarial resistance orthologs as well as vaccine candidate orthologs. We also found that P. malariae has a uniquely low nucleotide diversity and is generally atypical among the human malaria species, which may be associated with its unique methods of infecting and persisting in human hosts.

Plasmodium ovale spp.

P. ovale curtisi and P. ovale wallikeri are neglected relapsing malaria species with poorly understood biology. My graduate student mentee, Dr. Kelly Carey-Ewend, led a population genomics analysis of both species in sub-Saharan Africa in collaboration with researchers at UNC, Brown, the Ethiopian Public Health Institute, SANRU Asbl, Kinshasa School of Public Health, UMass Chan Medical School, the London School of Hygiene and Tropical Medicine, the National Institute for Medical Research (Tanzania), University of Dschang, and Muhimbili University of Health and Allied Sciences. His analyses demonstrated strong geographic population structure, signatures of selective sweep on the antimalarial resistance ortholog dihydrofolate reductase (Podhfr) and balancing selection on the vaccine candidate ortholog merozoite surface protein 1 (Pomsp1).

I am now supervising a much larger-scale population genomic analysis of P. ovale spp., which is led by Dr. Wenqiao He, with significant contributions from UNC undergraduate student Valerie Kim. I am also part of an ongoing, NIH-funded collaboration in Cameroon on the biology of relapsing malaria (primarily P. ovale spp.) in Africa, incorporating both parasite and vector biology.

Plasmodium vivax

P. vivax is the most geographically widespread human malaria species, and causes most malaria-related morbidity in Latin America and South and Southeast Asia. Like P. ovale spp, P. vivax has a dormant liver stage that can lead to relapse infections without a new infectious mosquito bite. In collaboration with researchers at UNC, Brown, and UMass Chan Medical School, I developed the broadest available genotyping panel for P. vivax, which we deployed on clinical samples collected in the Peruvian Amazon by Dr. Hugo Valdivia at NAMRU South.

My student Bhairavi Rajasekar led a genomic analysis of known relapses, which she compared to the background P. vivax population in Cambodia to determine if there were any genomic signatures of relapse tendency. Her work showed that relapses are very common in the background population.

Evolution of Host Preference in African Malaria Mosquitoes

Two major factors determine whether mosquitoes are good malaria vectors:

1. high vector competence (i.e. ability for parasites to grow and develop in mosquito midgut)
2. high anthropophily (preference to feed on human hosts)

My research focuses primarily on the question of host preference, both as it relates to behavior, and as it relates to the genomic basis of that behavior. The Anopheles gambiae species complex is uniquely well-suited to studying these questions, as it contains at least 11 closely-related species with distinct host preferences:

Highly anthropophilic: An. coluzzii, An. gambiae sensu stricto

Anthropophilic: An. arabiensis

Generalists: An. melas, An. merus

Zoophilic: An. amharicus, An. quadriannulatus

Mosquitoes rely on a variety of different stimuli to locate and assess hosts, including visual cues, thermal cues, and chemical cues (my focus). My doctoral research focused on chemosensory genes and anatomy and their influence on vertebrate host preference. This work incorporated differential gene expression analysis in the chemosensory organs, behavioral experiments to determine which organs are most important in driving host preference, and molecular evolutionary analysis of the gustatory receptor genes within the An. gambiae complex.

My current work aims to expand the geographic scope of African mosquito sample sequencing along with targeted sequencing approaches to improve coverage of the chemosensory genes, which will allow me to expand my existing work and resolve some existing gaps.

Host-Seeking Behavior in North American Mosquitoes

In addition to my work on African mosquito biology, I am also interested in the behavioral ecology of North American mosquitoes, especially the competent malaria vector Anopheles quadrimaculatus and the treehole mosquito and virus vector Aedes triseriatus. This work is driven by five major questions:

1. Is host preference plastic or static?
2. Which organs influence vertebrate and nectar host preference?
3. Which organs influence mating behavior?
4. What do immature mosquitoes sense?
5. How does chemosensory gene expression vary by sex, life stage, nutritional status, exposure to host volatiles, and other factors?