Interest in global health among applicants to medical schools, residency programs, and infectious disease fellowships has grown enormously in recent years, but the career development pathways for translating this interest into successful academic careers remain poorly defined and perilous, with relatively few mentors available in academia. The candidate for this K24 Award is an Associate Professor of Pediatrics and Medicine who has established a funded research program to investigate the immune response to childhood malaria and identify in vitro correlates of protective immunity among children in high transmission settings. This research program is based upon strong collaborative relationships with leading malaria epidemiologists and clinical trialists working in Uganda. The PI and her collaborators have forged an effective multidisciplinary team and have built substantial research infrastructure to conduct field studies in Tororo, Uganda, a setting of exceptionally high malaria transmission intensity. Malaria is the leading cause of pediatric deaths in Uganda and claims the life of more than one million children worldwide each year. The need for an effective vaccine against malaria is self-evident. However the iterative process of vaccine development, refinement, and testing would be greatly aided by a better understanding of the immunologic effector mechanisms that confer protection from malaria, as well as immune subversion mechanisms that may hinder the development of durable immunity. Our current understanding of the mechanisms of immune protection from malaria is very limited, and comes mostly from experimental vaccination studies of animals and humans. To date, population-based studies of the malaria-specific T cell response among children naturally exposed to malaria have been few in number and limited by shortcomings in study design. The proposed studies will use samples obtained from well-characterized pediatric cohorts to identify correlates of protective immunity to malaria, and to determine how the natural acquisition of antimalarial immunity is altered by chemopreventive interventions and by prenatal exposure to malaria and to HIV. In addition, this award will enable the candidate to branch into new areas of investigation including the role of semi-innate ?? T cells in malaria infection and clinical tolerance. The primary goal of this K24 will be to develop a cohort of young investigators with the skills require to conduct high quality translational immunology research, encourage their passion for patient-oriented global health research, and help them to become successful independent investigators. Trainees will include U.S. physician scientists at all levels - infectious disease fellows, post-doctoral scholars, residents, and students - working side by side with Ugandan scientists and students to conduct innovative immunology research in a region of exceptionally high malaria transmission intensity, while capacitating U.S. and Ugandan researchers to work in collaborative teams.

Public Health Relevance

The goals of this training program are to provide mentoring to early stage investigators in the conduct of patient-oriented global health research in children, and to further develop the research and mentoring capabilities of the applicant. Mentoring of students, residents, and post-doctoral fellows will be performed in the context of the applicant's established research program, which seeks to define correlates of naturally acquired immunity to malaria in Ugandan children.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
1K24AI113002-01
Application #
8759612
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Rao, Malla R
Project Start
2014-06-03
Project End
2019-05-31
Budget Start
2014-06-03
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$183,061
Indirect Cost
$13,560
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Sullivan, Richard T; Ssewanyana, Isaac; Wamala, Samuel et al. (2016) B cell sub-types following acute malaria and associations with clinical immunity. Malar J 15:139
Kakuru, Abel; Jagannathan, Prasanna; Muhindo, Mary K et al. (2016) Dihydroartemisinin-Piperaquine for the Prevention of Malaria in Pregnancy. N Engl J Med 374:928-39
Farrington, Lila A; Jagannathan, Prasanna; McIntyre, Tara I et al. (2016) Frequent Malaria Drives Progressive Vδ2 T-Cell Loss, Dysfunction, and CD16 Up-regulation During Early Childhood. J Infect Dis 213:1483-90
Odorizzi, Pamela M; Feeney, Margaret E (2016) Impact of In Utero Exposure to Malaria on Fetal T Cell Immunity. Trends Mol Med 22:877-888
Prahl, Mary; Jagannathan, Prasanna; McIntyre, Tara I et al. (2016) Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation. Malar J 15:497
Jagannathan, Prasanna; Bowen, Katherine; Nankya, Felistas et al. (2016) Effective Antimalarial Chemoprevention in Childhood Enhances the Quality of CD4+ T Cells and Limits Their Production of Immunoregulatory Interleukin 10. J Infect Dis 214:329-38
Boyle, Michelle J; Jagannathan, Prasanna; Bowen, Katherine et al. (2015) Effector Phenotype of Plasmodium falciparum-Specific CD4+ T Cells Is Influenced by Both Age and Transmission Intensity in Naturally Exposed Populations. J Infect Dis 212:416-25
Jagannathan, Prasanna; Nankya, Felistas; Stoyanov, Cristina et al. (2015) IFNγ Responses to Pre-erythrocytic and Blood-stage Malaria Antigens Exhibit Differential Associations With Past Exposure and Subsequent Protection. J Infect Dis 211:1987-96
Boyle, Michelle J; Jagannathan, Prasanna; Farrington, Lila A et al. (2015) Decline of FoxP3+ Regulatory CD4 T Cells in Peripheral Blood of Children Heavily Exposed to Malaria. PLoS Pathog 11:e1005041
Sullivan, Richard T; Kim, Charles C; Fontana, Mary F et al. (2015) FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium falciparum Exposure. PLoS Pathog 11:e1004894

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