Juliano - ideel

Mentoring in Translational Malaria Genomics

This mid-career mentoring award is dedicated to developing the next generation of patient-oriented researchers in infectious disease, with a particular focus on guiding clinicians, including Infectious Disease fellows and MD/PhD students, into successful translational research careers. Mentees receive individualized, hands-on guidance through every stage of the research process, from developing research questions and study design to grant writing, data analysis, and publication. Beyond scientific skills, trainees are supported in building communication, leadership, and professional development skills, with regular one-on-one meetings and a personalized development plan tailored to each mentee's goals and aspirations. The program is committed to fostering a diverse, equitable, and inclusive training environment, ensuring that trainees of all backgrounds have the support and opportunities they need to thrive as independent researchers.

Relapsing Malaria in Africa

The Relapsing Malaria in Africa (ReMA) program investigates two neglected but increasingly common forms of malaria — Plasmodium vivax and Plasmodium ovale. Working at a field site in Dschang, Cameroon, the team, including University of Dschang, CPC, and the University of Florida, is studying how these "relapsing" malarias spread from person to mosquito, how often they cause recurring infections through dormant liver stages called hypnozoites, and how Plasmodium vivax has evolved the ability to infect individuals previously thought to be immune. Using genomic sequencing, single-cell transcriptomics, and an innovative in vitro model system using P. knowlesi adapted to Duffy-negative invasion, the program is generating foundational data on transmission biology, relapse patterns, and parasite invasion mechanisms that have been almost entirely absent for these species in Africa. Ultimately, this work will fill critical knowledge gaps and inform the design of more effective malaria control strategies for these resilient and understudied parasites.

Zanzibar and Imported Malaria

The Zanzibar and Imported Malaria (ZIM) program tackles one of the final hurdles in malaria elimination — understanding how malaria is imported into near-elimination settings and how it spreads locally once introduced. Working in the Zanzibar Archipelago, where malaria has been dramatically reduced but not eliminated, the team, including Brown University, Imperial College London and Muhimbili University of Health and Allied Sciences, combines parasite genomic sequencing, human mobility data, and enhanced surveillance activities with the Zanzibar Malaria Elimination Program to identify where imported malaria is coming from and which communities are most at risk. By tracking highly related parasites between Zanzibar and mainland Tanzania using cutting-edge identity-by-descent methods, the program will map importation hotspots, define risk factors for both importation and local transmission, and evaluate how well current reactive case detection strategies are working to interrupt transmission chains. The findings will directly inform targeted malaria control strategies in Zanzibar and provide a broadly applicable framework for other regions facing similar challenges in achieving the final steps of malaria elimination.

ARTR in Rwanda

This research project is led by a multi-PI team of Dr. Jeffrey Bailey (Brown University), Dr. Jonathan Juliano (University of North Carolina at Chapel Hill), and Dr. Jean-Baptiste Mazarati (University of Global Health Equity, Rwanda). The project investigates the emergence and spread of artemisinin resistance in Rwanda and surrounding East African countries. Artemisinin combination therapies (ACTs) are the frontline treatment for Plasmodium falciparum malaria across Africa, where the disease causes the majority of global morbidity and mortality. Recent studies in Rwanda have identified a validated artemisinin resistance mutation (R561H in the kelch13 gene) arising independently within Africa — not imported from Southeast Asia — raising urgent public health concerns. To address this threat, the team brings together genomics and bioinformatics expertise at Brown University and UNC Chapel Hill, on-the-ground field and laboratory capacity in Rwanda (INES-Ruhingeri), Uganda (Mbarara University of Science & Technology, led by Dr. Edgar Mulogo), the DRC (Heal Africa, led by Dr. Stan Hagi), and Tanzania (National Institute for Medical Research, led by Dr. Deus Ishengoma), with world-leading mathematical modeling of drug resistance at Imperial College London (Dr. Lucy Okell and Prof. Azra Ghani). Together, these partners will map the geographic spread of resistance over time, identify additional resistance-associated mutations, study parasite fitness, and develop predictive models to forecast resistance spread and inform malaria control policy across the region.

Understanding emerging artemisinin partner drug resistance in East Africa

This project, led jointly by investigators at the University of Notre Dame and Brown University, addresses a critical and emerging public health threat: high-level resistance to lumefantrine, the partner drug in artemether-lumefantrine (AL), the most widely used first-line treatment for Plasmodium falciparum malaria in Africa. The project is motivated by a unique biobank of parasite isolates collected at the UK Malaria Reference Laboratory from travelers returning to the UK after failing AL treatment in Africa, including two isolates from Uganda representing the highest levels of stable lumefantrine resistance ever documented in culture. Using a multi-pronged approach, the team will: characterize and bank new resistant clinical isolates as they are identified (Aim 1); apply cutting-edge multi-omics techniques, including telomere-to-telomere genome sequencing, single-cell RNA sequencing, bulk transcriptomics, and proteomics, integrated through machine learning, to identify the genetic and molecular mechanisms underlying resistance (Aim 2); and conduct experimental genetic crosses in a humanized mouse model combined with bulk segregant analysis and CRISPR gene editing to definitively map and validate the genetic determinants of lumefantrine resistance (Aim 3). Together, these studies aim to deliver validated molecular markers and mechanistic insights urgently needed to monitor and counter this emerging resistance before it becomes a continent-wide crisis.

Spatial Models with AI for Antimalarial Resistance Trends

The Spatial Models with AI for Antimalarial Resistance Trends (SMAART) program applies cutting-edge artificial intelligence — specifically deep learning surrogate (DLS) models — to one of the most urgent threats in malaria control: the emergence and spread of artemisinin partial resistance across Sub-Saharan Africa. By training deep neural networks on complex malaria transmission simulations, the program creates lightweight "surrogate" models that can rapidly estimate key biological parameters, such as how strongly drugs select for resistance and how quickly resistant parasites spread across a landscape, analyses that were previously computationally impossible. The program brings together a uniquely powerful multinational team of malariologists, genomicists, modelers, medical geographers, and AI experts from UNC Chapel Hill, Imperial College London, the University of Oxford, Brown University, and the University of South Carolina, working in close partnership with national malaria control programs in the DRC and Ethiopia, the Ethiopian Public Health Institute, and collaborators supported by the CDC, World Bank, and Gates Foundation. Leveraging some of the largest malaria genomic datasets in the world, the team will use these models to make short-term predictions about the spread of resistance, evaluate the impact of different drug policy interventions, and produce openly available web-based tools that allow national malaria control programs to directly apply these powerful models to emerging drug resistance threats.

Malaria Vaccine Research

Our group has made significant contributions to malaria vaccine research, with a particular focus on understanding how parasite genetic diversity and local transmission dynamics influence vaccine performance. Working closely with colleagues at UNC and international partners in Africa, we have been involved in studies examining the efficacy of the RTS,S/AS01 malaria vaccine, the world's first approved malaria vaccine, across multiple sites in Africa, including Malawi, Ghana, and Gabon. Our work has helped elucidate how environmental factors, local transmission intensity, and parasite antigenic diversity can modify vaccine efficacy and the durability of protection. Using deep sequencing tools developed in his laboratory, Dr. Juliano has characterized genetic diversity in key vaccine target antigens, including the circumsporozoite protein (CSP) that is the basis of the RTS,S vaccine, examining how this variation may affect immune responses and ultimately protection. He has also served as investigator for the WHO RTS,S Effectiveness Trial in Malawi and is currently working as part of a team evaluating malaria vaccine performance in Kenya using systems immunology approaches.

Molecular Epidemiology of Bacterial Antimicrobial Resistance

We have pursued a meaningful body of work in bacterial antimicrobial resistance (AMR) epidemiology, spanning both high-income clinical settings in the United States and low- and middle-income countries in sub-Saharan Africa. In the United States, we have applied next-generation sequencing to investigate outbreaks of multidrug-resistant organisms, using genomic approaches to resolve transmission dynamics, characterize resistance mechanisms, and inform infection control. This work extends to understanding within-host evolution of bacterial populations and how selective pressures shape the emergence and persistence of resistance. Beyond single institutions, we have contributed to community-level surveillance efforts, examining the circulation and spread of high-risk resistant lineages across healthcare networks. Internationally, our work has leveraged genomic epidemiology to study antimicrobial resistance in diverse settings, including hospital- and community-based populations in sub-Saharan Africa, and to evaluate how clinical and public health interventions influence the burden and distribution of resistance genes.

Antimalarial, Resistance, Molecular Surveillance, Genomic Tools, and Clinical Trials

Historically, we have applied genomic and molecular epidemiology approaches to understand and combat antimalarial drug resistance, integrating field studies, clinical trials, and method development. Across diverse settings in Africa and beyond, we use next-generation sequencing and targeted genotyping to track the emergence and spread of resistance mutations (including K13 variants), quantify selection pressures, and map parasite population structure. We develop and deploy scalable tools, such as highly multiplexed amplicon sequencing and molecular inversion probe platforms, to enable high-resolution surveillance and relatedness inference. In parallel, we advance methods for clinical trial molecular (PCR) correction, improving the accuracy of efficacy estimates and interpretation of treatment outcomes. Together, this work links parasite genomics with clinical and public health data to inform policy, guide interventions, and strengthen malaria control and elimination efforts.

Epidemiology of Non-Falciparum Malaria

We investigate the epidemiology, biology, and public health significance of non-falciparum malaria species, including Plasmodium ovale, P. malariae, and P. vivax. Using molecular and genomic tools, we have shown that these species are more prevalent than previously appreciated, particularly in asymptomatic and low-density infections that are often missed by routine diagnostics. Our work integrates field studies across Africa with advanced detection methods, including species-specific PCR and sequencing approaches, to better define transmission dynamics, species interactions, and reservoirs of infection. We also examine how non-falciparum species contribute to ongoing transmission in both high- and low-endemic settings, and how they respond to current control strategies. Through these efforts, we aim to ensure that malaria elimination programs account for the full diversity of Plasmodium species and do not overlook hidden reservoirs that could undermine progress.

Organisms Beyond Malaria and Antimicrobial Resistance

Beyond malaria and AMR studies, we apply molecular and genomic epidemiology approaches to investigate a range of infectious diseases across clinical and community settings. Our work includes studies of respiratory infections and antimicrobial use in children, sexually transmitted infections such as Treponema pallidum, viral pathogens including SARS-CoV-2, and vector-borne and parasitic infections beyond Plasmodium. We use sequencing and advanced diagnostics to resolve outbreak transmission dynamics, characterize pathogen diversity, and identify sources of spread. Work on improving clinical decision-making through diagnostics, including studies demonstrating how point-of-care C-reactive protein (CRP) testing can safely reduce unnecessary antibiotic use in resource-limited settings, is an important collaborative advance. Across both hospital-based and community surveillance studies, we integrate genomic, clinical, and epidemiologic data to generate actionable insights that strengthen public health responses and improve patient care.

Supporting International Centers for Excellence in Malaria Research (ICEMRs)

We have contributed to the NIAID International Centers of Excellence for Malaria Research (ICEMR) program, a global network designed to advance multidisciplinary malaria research in endemic settings and generate evidence to inform control and elimination strategies. We collaborated with both the West/Central Africa EMERGENTS ICEMR and the South and Central Africa ICEMR, working across diverse transmission settings to study malaria epidemiology, parasite genetics, and intervention impact. These centers integrate field-based surveillance with genomic and translational approaches to better understand transmission dynamics and guide policy-relevant interventions. Through these partnerships, we contributed to efforts linking molecular data with clinical and population-level insights, helping to strengthen regional research capacity and inform malaria control programs across Africa.

Supporting Randomized Clinical Trials

We support the design, implementation, and analysis of randomized clinical trials to evaluate interventions for malaria prevention and treatment across diverse settings. Our work spans field-based trials and secondary analyses, where we apply molecular and genomic tools to strengthen outcome measurement, including distinguishing recrudescence from reinfection through molecular correction. By integrating clinical, laboratory, and epidemiologic data, we improve the accuracy and interpretability of trial results and generate evidence that directly informs policy and practice.