Renowned geneticist and parasitologist Jane Carlton's ultimate goal is what is referred to, in her field of malaria research, as the "e word": eradication. Advancements in this field, Carlton says, often lead to more questions than they answer, moving the research forward in new directions.
"Ultimately, we want to eradicate malaria," Carlton says. "The way I approach that is by asking questions about the malaria parasite's genome and how it works in order to try to develop better methods to control the parasite. I start with one piece of data—my basic building block is a genome. Once I sequence a genome and identify all of the genes and non-coding regions, that then leads to lots of other questions."
Carlton, who joined Johns Hopkins University last summer as the new director of the Johns Hopkins Malaria Research Institute, has been announced as a Bloomberg Distinguished Professor of Malaria Genomics and Global Public Health. She holds primary appointments in the Department of Molecular Microbiology and Immunology in the Bloomberg School of Public Health and in the Department of Biomedical Engineering, a department shared by the Whiting School of Engineering and the School of Medicine.
"We are excited to welcome Dr. Carlton as a Bloomberg Distinguished Professor," says Johns Hopkins University Provost Ray Jayawardhana. "Her impactful career has been defined by a cross-disciplinary approach that integrates genomics, computational biology, epidemiology, and global health efforts to combat malaria. Dr. Carlton's leadership in establishing partnerships with local researchers and clinicians in malaria-endemic regions will be invaluable in fostering collaborations across Johns Hopkins and advancing the effort to eradicate this deadly disease."
Carlton uses tools of comparative genomics to study the biology and evolution of different species of parasites, with a particular focus on Plasmodium, the parasite that causes malaria. Comparative genomics uses a variety of tools to compare the complete genome sequences of different species to pinpoint regions of similarity and difference. By comparing the genomes of malaria parasites, Carlton hopes to interrogate their biology and determine how the organism has evolved, in order to ultimately use this information to develop more effective drugs, identify potential vaccine targets, and develop better diagnostic methods.
"By gaining a better understanding of a parasite's genome, you can find the chinks in its armor, the areas where you can target the parasite," Carlton explains. "For instance, if you find a protein that is highly conserved—meaning it is similar either within a genome or across species, indicating that it has been maintained by natural selection—you can try to target that in a vaccine, or perhaps use it to develop a diagnostic test. Similarly, gaining insight into mosquitos' olfactory genes, which impact their sense of smell, can provide an indication on how to prevent a mosquito from searching out people to bite and transmit the parasite onto."
More recently, Carlton is developing a systems biology approach—using interdisciplinary, holistic methods that combine diverse biological datasets with computational and integrative analysis and modeling of complex biological systems. She uses datasets from multiple "omics" fields, which aim to collectively characterize the groups of biological molecules that translate into the structure, function, and dynamics of an organism in order to obtain a more comprehensive understanding of biological systems and the complex relationships and patterns within them. In addition to Carlton's area of expertise, genomics, other omics fields include proteomics, the systemic analysis of proteins produced by a cell, organ or organism; transcriptomics, the study of the set of all RNA molecules; and metabolomics, the study of metabolites within cells, biofluids, tissues, or organisms. Carlton says malaria research has much to gain from the interdisciplinary systems biology approach, and collaborations are crucial to advance research in this area. She hopes to introduce systems biology research at the Johns Hopkins Malaria Research Institute.
"When you decode a genome, you need powerful computing and statistical methods to analyze that data, so a lot of the members of my lab are computational biologists who use bioinformatics tools for data analysis," Carlton explains. "Taking a holistic approach also requires many other areas of expertise. A lot of the global health projects I undertake involve epidemiologists, and when you have a parasite that affects humans, it triggers the immune response, so you need immunologists as well. In addition, it is important to include physicians, nurses, and public health practitioners."
Carlton has led projects to decode the genomes, the complete set of genes present in an organism, of several different malaria parasite species, including the human malaria parasites Plasmodium vivax—the most frequent and widely distributed cause of recurring malaria in humans—and Plasmodium falciparum—the deadliest species of Plasmodium that causes malaria in humans.
"Parasites are fascinating," Carlton says. "They have evolved machinery to evade the immune response. They are very sneaky in the mechanisms that they have developed for drug resistance and to evade vaccines. For instance, rapid diagnostic tests (similar to those used for COVID-19) exist for malaria, but unfortunately, the parasite has evolved and the marker that is usually detected in a malaria rapid test has been deleted from the genome, so someone can be infected with parasites but they are not detected using the rapid test. We hope to develop new targets for rapid diagnostic tests to enable easier detection of malaria parasites based on metabolites produced either by the parasite or by the human host in response to the infection."
Carlton established and served as the program director for the Center for the Study of Complex Malaria in India (CSCMi), one of 10 National Institutes of Health-funded International Centers of Excellence for Malaria Research (ICEMR). The CSCMi aims to help develop knowledge, tools, and evidence-based strategies to support Indian malaria intervention and control programs, and to build malaria research capacity in India, in partnership with local researchers, clinicians, and public health workers at several institutes. In addition to studying malaria parasite genomes, projects at CSCMi range from behavioral studies (such as examining how people protect themselves from mosquitoes) to drug resistance and epidemiology (for instance, how a very wet rainy season impacts disease transmission). The center also provides technology transfer and training in a range of methods including study design, epidemiology data collection, genomics and molecular biology, so that local scientists can continue this research. For Carlton, the importance of partnering with local collaborators cannot be overstated.
"It is easy for scientists to be stuck away in a laboratory, studying a disease or parasite," says Carlton. "When you're working with infectious diseases, it's crucial to keep sight of the fact that this is a very real-life problem, and you need to be closer to the people it affects. Being able to go out into the communities where people are infected with malaria is vital in order to take a holistic approach to studying the disease."
The Johns Hopkins Malaria Research Institute is also home to another NIH ICEMR, Malaria Transmission and the Impact of Control Efforts in Southern and Central Africa, led by William Moss, professor in the departments of Epidemiology, International Health, and Molecular Microbiology and Immunology, and executive director of the International Vaccine Access Center. Carlton hopes to broaden work at the institute by building on these existing partnerships and expanding to new field sites.
"My vision is to build even more bridges between the Johns Hopkins Malaria Research Institute and researchers in developing countries," says Carlton. "Making connections, and enabling researchers from these countries to come to the Institute to set up collaborations will greatly strengthen our work."
Carlton came to JHU from New York University, where she was the Julius Silver, Roslyn S. Silver, and Enid Silver Winslow Professor in the Department of Biology and the School of Public Health; and faculty director of genomic sequencing at the Center for Genomics and Systems Biology.
Carlton earned her Bachelor of Science in biological sciences genetics and her PhD in genetics at the University of Edinburgh. She completed a postdoctoral fellowship at the Institute of Cell, Animal and Population Biology at the University of Edinburgh. Before joining the faculty at New York University, she spent time as a postdoctoral associate and assistant scientist in the Department of Pathobiology at the University of Florida, Gainesville, a visiting scientist at the National Center for Biotechnology Information ("GenBank") at the National Institutes of Health, and an associate scientist at the Institute for Genomic Research (now the J. Craig Venter Institute).
"Coming to Johns Hopkins is my dream," Carlton says. "Being able to study malaria at an institute where the faculty and staff do such wonderful research, and having access to so many fantastic like-minded colleagues who work on malaria, but also a range of other fields such as computational biology and genomics, with knowledge that I can call upon will really move my research forward."
"We are at a critical moment in the fight against malaria, and I am thrilled to have Dr. Carlton's deep experience and fresh perspective at the Bloomberg School's Malaria Research Institute," says Ellen J. MacKenzie, dean of the Bloomberg School of Public Health. "Under her leadership, we are bringing continued vigilance and innovative thinking to a complex disease, and we are poised to make significant progress in the years to come."
"Dr. Carlton is a visionary scholar whose embracing of the critical role collaboration will play in eradicating malaria makes her a wonderful addition to our community," says Ed Schlesinger, dean of the Whiting School of Engineering. "I know our faculty are eager to work with her and contribute to her success."
As a Bloomberg Distinguished Professor, Carlton joins an interdisciplinary cohort of scholars working to address major world problems and teach the next generation. The program is backed by support from Bloomberg Philanthropies, which is also the lead funder of the Johns Hopkins Malaria Research Institute.
