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Indiana University School of Medicine
Indiana University School of Medicine
Dr. Tran is a physician-scientist who began studying malaria as a graduate student in the laboratory of Dr. Mary Galinski at Emory University. After completing his Internal Medicine residency at the Johns Hopkins Hospital and a clinical fellowship in Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID), he trained as a post-doctoral fellow with Dr. Peter Crompton in the Laboratory of Immunogenetics at NIAID, where he studied naturally acquired immunity to falciparum malaria in a prospective cohort study conducted in Mali.

Tran Lab

The Tran Lab uses systems-based approaches to investigate both naturally acquired and vaccine-induced immunity to malaria in close collaboration with international research teams. The major questions driving our research are:

1. How do malaria-exposed individuals learn to tolerate Plasmodium infections, sometimes at parasite densities in the blood of hundreds of thousands of parasites per microliter?

2. Which immune responses induced by either natural infections or candidate malaria vaccines are associated with protection from malaria infection and disease?

By performing integrative analyses of high-dimensional immunological data generated from well-designed cohort studies, we aim to identify molecular predictors of malaria outcomes and elucidate the mechanisms governing immune responses that protect the host from infection and/or disease.

Our lab also studies the impact of asymptomatic malaria infection and inflammation on the cognitive performance of schoolchildren living in malaria-endemic areas of Western Kenya. We have been funded by the Doris Duke Foundation, Indiana CTSI, the Showalter Trust, and the National Institutes of Health.

Biography

I study the host response to malaria in endemic populations. While a graduate student at Emory University, I evaluated immune responses to Plasmodium vivax malaria vaccine candidates in residents of the Brazilian Amazon. After graduating from Emory’s Medical Scientist Training Program, I completed clinical training in Internal Medicine at the Johns Hopkins Hospital and Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID). I pursued additional post-doctoral training in Peter Crompton’s research group at NIAID, where I studied naturally acquired immunity to falciparum malaria in a cohort study conducted in Mali. I am currently a tenured Associate Professor of Medicine and Pediatrics at the Indiana University School of Medicine, where I lead a research group that focuses on understanding malaria immunity. In addition to my research, I also attend on the Infectious Diseases inpatient consultation service at the Indianapolis VA Medical Center, where I help train medical students, residents, and fellows while taking care of our Veterans.

Infectious Disease Research

The Division of Infectious Diseases faculty at IU School of Medicine have an active research portfolio supported by NIH, CDC, various foundations and industry. It includes basic science research in bacterial pathogenesis, HPV, malaria, HIV and toxoplasmosis. Faculty investigators in this division also conduct clinical prevention and treatment trials in HIV, HPV and a variety of sexually transmitted infections (STIs); diagnostic trials for STIs; epidemiologic studies of STIs, HIV, HPV and malaria; and implementation science research in HIV.
5188-Tran, Tuan

Tuan M. Tran, MD, PhD

Associate Professor of Medicine

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Malaria researchers administer a blood test to a small child.

Current Funded Research Projects

Malaria caused by the Plasmodium parasite remains a global health threat, affecting ~249 million people and leading to more than 600,000 deaths per year. Understanding the mechanisms contributing to pathological inflammation during malaria and the processes that govern the control of malaria parasites within the host can provide insight for the development of adjunctive therapies against this deadly infection. Using human samples and relevant model systems, we are studying the interactions between multiple stages of the Plasmodium parasite and p53 pathways within relevant host tissues and how such interactions impact malaria pathogenesis and infection biology. Results from this study will provide mechanistic insight into the role of p53 in modulating malaria-induced pathogenesis and liver-stage infection, with the goal of identifying druggable targets for interventions aimed at mitigating malaria disease severity and/or liver-stage prophylaxis. Learn more: "Evaluating the role of P53 pathways in malaria" NIH Reporter.

Asymptomatic malaria infections caused by the Plasmodium falciparum parasite, while not clinically apparent, have significant individual and public health consequences, including chronic anemia, susceptibility to bacterial infections, and maintenance of onward transmission by serving as parasite reservoirs. Such infections can also adversely impact cognitive performance in school-aged children, but the potential mechanisms by which this occurs has not been well-studied. In this project, which is currently being conducted in an area of Western Kenya with intense malaria transmission, we are measuring cognitive performance and blood markers of inflammation in apparently healthy (asymptomatic) schoolchildren, some of whom are naturally infected with P. falciparum, to determine whether treatment of these asymptomatic infections leads to improvements in cognitive performance by reducing systemic inflammation. Learn More: "Assessing the Impact of Treatment of Asymptomatic Malaria Infections on Inflammation and Cognition in Schoolchildren" NIH Reporter.

Current Research Group Members

Erik Gaskin

Erik L. Gaskin, MS

Laboratory Manager

27456-Bhardwaj, Jyoti

Jyoti Bhardwaj, PhD

Assistant Scientist in Medicine

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59881-Holla, Prasida

Prasida Holla, PhD

Assistant Research Professor of Pediatrics

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Select Recent Publications (since 2022)

Holla P, Bhardwaj J, Tran TM. Mature beyond their years: young children who escape detection of parasitemia despite living in settings of intense malaria transmission. Biochem Soc Trans. 2024 Jun 26;52(3):1025-1034. doi: 10.1042/BST20230401. Review. PubMed PMID: 38752830; PubMed Central PMCID: PMC11209762.

Heruye SH, Myslinski J, Zeng C, Zollman A, Makino S, Nanamatsu A, Mir Q, Janga SC, Doud EH, Eadon MT, Maier B, Hamada M, Tran TM, Dagher PC, Hato T. Inflammation primes the murine kidney for recovery by activating AZIN1 adenosine-to-inosine editing. J Clin Invest. 2024 Jul 2;. doi: 10.1172/JCI180117. [Epub ahead of print] PubMed PMID: 38954486.

Johnson AE, Upadhye A, Knight V, Gaskin EL, Turnbull LB, Ayuku D, Nyalumbe M, Abuonji E, John CC, McHenry MS, Tran TM, Ayodo G. Subclinical Inflammation in Asymptomatic Schoolchildren With Plasmodium falciparum Parasitemia Correlates With Impaired Cognition. J Pediatric Infect Dis Soc. 2024 May 30;13(5):288-296. doi: 10.1093/jpids/piae025. PubMed PMID: 38512283.

Senkpeil L, Bhardwaj J, Little MR, Holla P, Upadhye A, Fusco EM, Swanson PA 2nd, Wiegand RE, Macklin MD, Bi K, Flynn BJ, Yamamoto A, Gaskin EL, Sather DN, Oblak AL, Simpson E, Gao H, Haining WN, Yates KB, Liu X, Murshedkar T, Richie TL, Sim BKL, Otieno K, Kariuki S, Xuei X, Liu Y, Polidoro RB, Hoffman SL, Oneko M, Steinhardt LC, Schmidt NW, Seder RA, Tran TM. Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine. JCI Insight. 2024 Apr 30;9(11). doi: 10.1172/jci.insight.167408. PubMed PMID: 38687615.

Ambegaonkar AA, Holla P, Sohn H, George R, Tran TM, Pierce SK. Isotype switching in human memory B cells sets intrinsic antigen-affinity thresholds that dictate antigen-driven fates. Proc Natl Acad Sci U S A. 2024 Mar 26;121(13):e2313672121. doi: 10.1073/pnas.2313672121. Epub 2024 Mar 19. PubMed PMID: 38502693; PubMed Central PMCID: PMC10990115.

Nziza N, Tran TM, DeRiso EA, Dolatshahi S, Herman JD, de Lacerda L, Junqueira C, Lieberman J, Ongoiba A, Doumbo S, Kayentao K, Traore B, Crompton PD, Alter G. Accumulation of Neutrophil Phagocytic Antibody Features Tracks With Naturally Acquired Immunity Against Malaria in Children. J Infect Dis. 2023 Sep 15;228(6):759-768. doi: 10.1093/infdis/jiad115. PubMed PMID: 37150885; PubMed Central PMCID: PMC10503956.

Bhardwaj J, Upadhye A, Gaskin EL, Doumbo S, Kayentao K, Ongoiba A, Traore B, Crompton PD, Tran TM. Neither the African-Centric S47 Nor P72 Variant of TP53 Is Associated With Reduced Risk of Febrile Malaria in a Malian Cohort Study. J Infect Dis. 2023 Jul 14;228(2):202-211. doi: 10.1093/infdis/jiad066. PubMed PMID: 36961831; PubMed Central PMCID: PMC10345479.

Complete List of Publications