Professor Thumbi Ndung’u is interested in understanding antiviral immune mechanisms and viral adaptation in HIV-1 subtype C infection as a pathway to vaccine development. His work has focussed on understudied populations and viral strains in resource-limited, high burden settings where knowledge of the role of antiviral immune responses, viral strains and associated genetic factors is likely to yield the greatest impact in terms of biomedical interventions like vaccines. Thumbi’s early work addressed the lack of biological tools for HIV vaccine and pathogenesis research on HIV-1 subtype C, the predominant subtype globally and in southern Africa. He generated and characterized the first infectious molecular of HIV-1 subtype C from primary isolates, and constructed the first infectious subtype C envelope-derived simian-human immunodeficiency virus able to replicate in rhesus macaque peripheral blood mononuclear cells. These tools were deposited in the NIH AIDS Reagent Program and remain available to researchers. The tools have facilitated in vitro and animal model studies of HIV-1 subtype C biology and vaccine development research.
Thumbi also actively participates in the training of graduate and postdoctoral researchers and has a special interest in capacity building for biomedical research in Africa. He is a member of AHRI Faculty, where he heads up a lab. He is an Investigator and Max Planck Institute for Infection Biology Research Group Leader. He is also a University of KwaZulu-Natal (UKZN) Professor and Victor Daitz Chair in HIV/TB Research, Adjunct Professor at the Harvard School of Public Health, the Scientific Director at UKZN’s HIV Pathogenesis Programme, the Programme Director for the Sub-Saharan African Network for TB/HIV Research Excellence and is the South African Research Chair in Systems Biology of HIV/Aids.
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The Ndung’u research group’s overarching goal is to understand how HIV and TB persist and replicate in the face of a hostile host immune system. Ultimately, the group hopes to use this knowledge to aid the design of a safe, affordable and effective HIV-1 vaccine. The group also studies non-immune host/pathogen interactions that may explain heterogeneity of clinical outcomes following exposure to HIV or TB. The group is also interested in HIV-1 diversity and its consequences for the spread of the epidemic. The group works with samples from donors who have immune systems that control HIV without antiretroviral (ARV) treatment – known as ‘controllers’ – as well as those who remain HIV negative despite exposure to the virus. These individuals may hold the key to vaccine development or novel therapies. The lab’s approach is to understand how innate and adaptive immune responses may prevent people from getting infected or lead to durable viral control in those already infected. The lab also interrogates the mechanisms that ultimately lead to loss of viral control and disease progression. Their TB research includes studies on immune responses in the lung, which is the primary site of exposure and infection. Ndung’u Group researchers use techniques in virology, immunology, molecular biology and genetics to help understand the complex interaction between the virus and the host. The Ndung’u Group places emphasis on biomedical research excellence, innovative thinking and capacity building for scientific discoveries likely to benefit resource-limited settings and address Africa’s public health problems.
Meet the Team
Emily B. Wong
Emily B. Wong trained in Internal Medicine at University of California San Francisco and in Infectious Diseases at the combined Harvard program at Massachusetts General Hospital and Brigham and Women's Hospital. Her postdoctoral training is in human HIV and TB immunology. She is currently an Instructor at Harvard Medical School, an attending in the Division of Infectious Diseases at the Massachusetts General Hospital and a Research Associate in the Ndung'u Laboratory at AHRI. Her research focuses on trying to understand the immune response to M.tb at the site of immune challenge - the respiratory mucosa.
Kamini Gounder was awarded her PhD in genomics from the University of Free State. She then joined the Ndung’u lab where her work focuses on host/virus interactions and viral diversity in HIV-1 infection. In particular, she has been investigating the impact of immune selection pressure on HIV-1 sequence evolution. This work has direct relevance to vaccine design, a critical goal in the HIV research field.
Daniel Muli Muema
Postdoctoral Research Fellow
Daniel Muli Muema completed his PhD training at Open University UK in collaboration with University of Liverpool and KEMRI-Wellcome Trust Research Programme. Having previously described the defects of B cells in HIV-infected children, Daniel is now investigating the causes of such defects. Since B cells produce antibodies that are the focus of current HIV vaccine research, understanding the mechanisms of B-cell defects in HIV will enable the design of vaccines that can elicit effective antibody responses against the virus.
Postdoctoral Research Fellow
Kavidha Reddy’s PhD focused on the study of the host restriction factor, APOBEC3G, and its role in HIV-1 subtype C infection. Her postdoctoral work in the Ndung’u Lab focuses on studying APOBEC3G genetic variants which occur at high frequencies in African populations and their influence on the evolution of the HIV-1 Vif protein in vivo as the virus adapts to ongoing APOBEC3G driven immune pressure.
Postdoctoral Research Fellow
Okechukwu Ndumnego did his doctoral studies at the University of Pretoria where he evaluated the protective immune responses elicited by recombinant/non-living anthrax vaccine candidates in goat and mouse models. His current research interest is primarily concerned with how Mycobacterium tuberculosis (Mtb) infection activity affect host protein responses. These proteins can serve as biomarkers of Mtb infection and risk predictors for TB development in HIV co-infected individuals.
Ngomu Akeem Akilimali holds a Master’s in Medical Science from UKZN. His Master’s research focussed on how the HIV-induced upregulation of Leukocyte Immunoglobulin (Ig)-Like Receptors is abrogated in individuals co-infected with Mycobacterium tuberculosis. His PhD work focuses on the investigation of immune activation and pathogen-specific immune response in cryptococcal meningitis-associated immune reconstitution inflammatory syndrome (C-IRIS).
Bongiwe Xulu holds a Master’s degree in Biochemistry from UKZN. Bongiwe’s work at AHRI focuses on understanding the immune response to HIV infected individuals and how infection alters immunity to M tuberculosis. She has also been working on studying the function and location of Mucosal invariant T (MAIT) cells immune response from bronchoalveolar lavage fluid compared to the peripheral blood.
Nicole Reddy holds an Honours degree in Medical Microbiology from the Nelson R Mandela School of Medicine. For Nicole’s Master’s project, she is characterising the anti-APOBEC3 activity of founder vif variants and longitudinally assessing vif sequences and functional changes over the course of one year of HIV infection, under the mentorship of Postdoctoral Fellow Kavidha Reddy.
Research Lab Technician
Thierry Basset holds an honours degree in Microbiology from Stellenbosch University. His work at AHRI focusses on trying to understand the immune response to HIV and Mycobacterium tuberculosis co-infections within the respiratory mucosa, and how Mucosal Associated Invariant T (MAIT) cells may differ to similar T-cells located elsewhere in the body.
Research Laboratory Technician
Sam Rasehlo completed his MSc at the University of Pretoria . His MSc work focused on determining the effects of cigarette smoke on antimycobacterial activity of anti-tuberculosis drugs on Mycobacterium tuberculosis biofilm. Sam is currently working with Dr Daniel Muema to determine the causes of B cell defects in HIV.
Selected Recent Publications
Catherine K. Koofhethile, Zaza M. Ndhlovu, Christina Thobakgale-Tshabalala, Julia G. Prado, Nasreen Ismail, Zenele Mncube, Lungile Mkhize, Mary van der Stok, Nonhlanhla Yende, Bruce D. Walker, Philip J.R. Goulder and Thumbi Ndung’u. (2016). CD8+ T cell breadth and ex vivo virus inhibition capacity distinguish between viremic controllers with and without protective HLA class I alleles. Journal of Virology, Jul 11;90(15):6818-31. doi: 10.1128/JVI.00276-16. Print 2016 Aug 1. PMID: 27194762.
Kavidha Reddy, Marcel Ooms, Michael Letko, Nigel Garrett, Viviana Simon and Thumbi Ndung’u. (2016). Functional characterization of Vif proteins from HIV-1 infected patients with different APOBEC3G haplotypes. AIDS, Jul 17;30(11):1723-9. doi: 10.1097/QAD.0000000000001113. PMID: 27064995.
Paradise Madlala, Ravesh Singh, Ping An, Lise Werner, Koleka Mlisana, Salim S. Abdool Karim, Cheryl A. Winkler, and Thumbi Ndung’u. (2016). Association of polymorphisms in the regulatory region of the cyclophilin A gene (PPIA) with gene expression and HIV/AIDS disease progression. Journal of Acquired Immune Deficiency Syndromes, Aug 15;72(5):465-73. doi: 10.1097/QAI.0000000000001028. PMID: 27088296.
Jonathan M. Carlson, Victor Y. Du, Nico Pfeifer, Anju Bansal, Vincent Y.F. Tan, Karen Power, Chanson J. Brumme, Anat Kreimer, Charles E. DeZiel, Nicolo Fusi, Malinda Schaefer, Mark A. Brockman, Jill Gilmour, Matt A. Price, William Kilembe, Richard Haubrich, Mina John, Simon Mallal, Roger Shapiro, John Frater, P. Richard Harrigan, Thumbi Ndung’u, Susan Allen, David Heckerman, John Sidney, Todd M. Allen, Philip J.R. Goulder, Zabrina L. Brumme, Eric Hunter, Paul A. Goepfert. (2016). Impact of Pre-adapted HIV Transmission. Nature Medicine, Jun;22(6):606-13. doi: 10.1038/nm.4100. Epub, May 16. PMID: 27183217.
Henrik N. Kløverpris, Samuel W. Kazer, Jenny Mjösberg, Jenniffer M. Mabuka, Amanda Wellmann, Zaza Ndhlovu, Marisa C. Yadon, Shepherd Nhamoyebonde, Maximilian Muenchhoff, Yannick Simoni, Frank Andersson, Warren Kuhn, Nigel Garrett, Wendy A. Burgers, Philomena Kamya, Karyn Pretorius, Krista Dong, Amber Moodley, Evan W. Newell, Victoria Kasprowicz, Salim S. Abdool Karim, Philip Goulder, Alex K. Shalek, Bruce D. Walker, Thumbi Ndung’u, Alasdair Leslie. (2016). Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression. Immunity, Feb 1. pii: S1074-7613(16)00030-3. doi: 10.1016/j.immuni.2016.01.006. [Epub ahead of print]. PMID: 26850658.