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 renewal is a Professor of Pediatrics and Medicine who has established a successful research and mentoring program to investigate the immune response to childhood malaria and identify in vitro correlates of protective immunity among children in highly malaria endemic 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 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. The candidate has established a systematic approach to mentoring both pre-doctoral students and early career clinician-investigators engaged in patient-oriented research. Several trainees have obtained NIH K Award support, and some have recently assumed independent faculty positions at leading research institutions. Mentoring will be provided in the context of the candidate's own funded research program, which provides numerous opportunities for add-on projects initiated by trainees. The proposed studies will use samples and data from well-characterized pediatric cohorts in Uganda 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. In addition, this award will address fundamental questions regarding how fetal T cells respond to pathogen-derived antigens encountered in utero. The primary goal of this K24 will be to mentor young investigators with the skills required to conduct high quality translational immunology research, encourage their passion for patient-oriented global health research, and help them to become successful independent investigators. Specific mentoring emphases during the K24 renewal period will be on helping trainees to acquire the skills in bioinformatics and genomic data analysis that are needed for emerging high-parameter single cell immune profiling approaches (mass cytometry, single cell RNA sequencing), and to foster the careers of women, under-represented minorities, and investigators from low-resource countries to become successful academic faculty members.

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 mentoring leadership 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, and to understand the impact of in utero antigen exposure on the development of immunity during childhood.

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 #
2K24AI113002-06
Application #
9821578
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Rao, Malla R
Project Start
2014-06-03
Project End
2024-06-30
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
6
Fiscal Year
2019
Total Cost
Indirect Cost
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
94118
Odorizzi, Pamela M; Jagannathan, Prasanna; McIntyre, Tara I et al. (2018) In utero priming of highly functional effector T cell responses to human malaria. Sci Transl Med 10:
Prahl, Mary; Jagannathan, Prasanna; McIntyre, Tara I et al. (2017) Sex Disparity in Cord Blood FoxP3+ CD4 T Regulatory Cells in Infants Exposed to Malaria In Utero. Open Forum Infect Dis 4:ofx022
Jagannathan, Prasanna; Lutwama, Fredrick; Boyle, Michelle J et al. (2017) V?2+ T cell response to malaria correlates with protection from infection but is attenuated with repeated exposure. Sci Rep 7:11487
Farrington, Lila; Vance, Hilary; Rek, John et al. (2017) Both inflammatory and regulatory cytokine responses to malaria are blunted with increasing age in highly exposed children. Malar J 16:499
Boyle, Michelle J; Jagannathan, Prasanna; Bowen, Katherine et al. (2017) The Development of Plasmodium falciparum-Specific IL10 CD4 T Cells and Protection from Malaria in Children in an Area of High Malaria Transmission. Front Immunol 8:1329
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
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
Farrington, Lila A; Jagannathan, Prasanna; McIntyre, Tara I et al. (2016) Frequent Malaria Drives Progressive V?2 T-Cell Loss, Dysfunction, and CD16 Up-regulation During Early Childhood. J Infect Dis 213:1483-90
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
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

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