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K-Rith

INVESTIGATOR

Thumbi Ndung’u

Thumbi Ndung’u grew up on a small coffee and dairy farm in a picturesque part of rural Kenya. He studied veterinary medicine at the University of Nairobi, Kenya, and was then offered a junior research position in schistosomiasis (bilharzia) vaccine development. He worked in a small laboratory with few resources but excellent scientific mentorship and won a scholarship to pursue further studies at Harvard University.  When he arrived there, he recalls it was almost too much to handle: “The laboratory shelves were groaning under the weight of reagents, books and work manuals. I hadn’t seen a flow cytometer or a PCR machine before, I hadn’t seen a computer before – and typing was required for assigned homework! I almost caught the next plane home…”  But he stayed on and years later was the recipient of the Edgar Haber award for outstanding and creative thesis work at Harvard.

By the time he finished his training, the devastation caused by HIV/Aids was clear and Dr Ndung’u eventually headed back home so that he could contribute directly to help solve what had become sub-Saharan Africa’s most pressing public health problem. “As an African, I am proud to be using the tools of science to attack some of the most significant global public health problems today, HIV/Aids and TB, and to help develop the next generation of globally competitive African scientists,” Dr Ndung’u says.

Get in touch with Thumbi Ndung’u via thumbi.ndungu@ahri.org 

ABOUT

Ndung'u Lab

The goal of the Ndung’u laboratory is to understand immune mechanisms against HIV and tuberculosis, and pathogen evasion of immune responses as a pathway to vaccine development.

Vaccines offer one of the most effective public health strategies against diseases. Vaccines are generally safe, highly effective and affordable. Unfortunately, there are no effective vaccines against HIV or TB and therefore the control of these diseases in resource-limited settings is problematic.  Our research goals are to understand how the immune system fights off persistent infections such HIV and TB and how the pathogens in turn evade or adapt to continuous immune pressure. We also study non-immune host/pathogen interactions that may explain heterogeneity of clinical outcomes following exposure to the pathogen or infection. Ultimately, we hope to use this knowledge to aid rational vaccine or therapeutics design against these two major killer diseases as well as other pathogens.

Our overarching goal is to understand how HIV and TB are able to persist and replicate in the face of a hostile host immune system.  Our laboratory focuses on individuals who remain HIV negative despite exposure to the virus and those infected who achieve some level of viral control without the help of antiretroviral therapies. These individuals may hold the key to vaccine development or novel therapies. Our 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. We also interrogate the mechanisms that ultimately lead to loss of viral control and disease progression. In the laboratory, we utilise techniques in virology, immunology, molecular biology and genetics to help us understand the complex interaction between the virus and the host. We place 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.

Ndung'u Lab

Meet the Team

Kwanele Gqunta

RESEARCH LABORATORY TECHNICIAN 

Kwanele Gqunta grew up in the city of Port Elizabeth in the Eastern Cape. He obtained his undergraduate, Honours and Masters degrees (Microbiology) at the Nelson Mandela Metropolitan University. His Masters degree focussed on the prevalence and molecular epidemiology of extended-spectrum beta-lactamase-producing and carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa in Port Elizabeth. Passion for scientific research led Kwanele to join K-RITH as a research laboratory technician under Dr Daniel Muli Muema. His current work focusses on the effects of Type I interferons on B cell responses in vitro.

Urisha Singh

POSTDOCTORAL FELLOW 

Urisha Singh is originally from Pietermaritzburg. She has a BSc in Bio-Medical Science, an Honours degree in Medical Biochemistry and an MSC in Biological Sciences from the University of KwaZulu-Natal (UKZN). For her PhD, which she did through the UKZN HIV Pathogenesis Programme, she investigated acquired and transmitted drug resistance in HIV-1 subtype C. Urisha joined the Ndung’u lab in 2016 as a Postdoctoral Research Fellow. She is exploring the immune microenvironment of lung tissue from HIV/TB co-infected individuals in order to elucidate potential pathways associated with increased susceptibility to TB infection of HIV infected people. This research could have important implications for the future development of treatments for HIV/TB co-infection.

Emily Wong

INTERNATIONAL COLLABORATOR

Emily B. Wong received her A.B. summa cum laude from Harvard College in History and Literature.  She received her M.D. from Harvard Medical School in 2006 and 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.  From 2008 – 2010 she was a Fogarty International Clinical Research Fellow at the University of Witwatersrand in Johannesburg, South Africa.  There she conducted a clinico-pathological autopsy study on the causes of early mortality for patients initiating antiretroviral therapy and found that TB caused over 80% of early deaths.  Since 2011, she has been based primarily at K-RITH where she has pursued post-doctoral training in human HIV and TB immunology in the Bishai and Ndung’u Laboratories.  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 K-RITH. Emily’s research focuses on trying to understand the immune response to M.tb at the site of immune challenge – the respiratory mucosa.  Her goal is to uncover mechanisms of control that will provide new insights for TB vaccine design.  She is also interested in the way that HIV-infection alters immunity to M.tb and how varying states of TB co-infection affect inflammation and immune activation in HIV-infected patients. In 2012 she started a prospective, ongoing cohort of patients undergoing bronchoscopy that allows her to compare immune responses in bronchoalveolar lavage fluid (lung washings) to those in the peripheral blood. She is currently particularly interested in Mucosal Associated Invariant T (MAIT) cells – an exciting class of innate-like T cells that she has found to be enriched and active in the lungs during tuberculosis.  She studies MAIT cells using a variety of techniques that include multi-colour flow cytometry, T cell receptor sequencing and single-cell and population-level transcriptional analysis. For her work on MAIT cells in the lungs in HIV and TB, Emily was awarded a Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious Diseases.  She is also the Principal Investigator of an NIH/NIAID Mentored Clinical-Scientist Career Development Award (K08) and a Harvard University Center for Aids Research (CFAR) Feasibility Project Grant.

Jenniffer Maroa

COLLABORATOR

Jenniffer Mabuka- Maroa was born and raised in Kisii, Kenya.  She obtained her Bachelors degree in Science in 1998 from Jomo Kenyatta University of Agriculture and Technology in Kenya. In 2012 she completed her PhD studies at the university of Washington, Seattle.  Until recently, she was involved in research aimed at evaluating the potential of immune factors in breast milk of HIV infected women in protecting infants against HIV acquisition. Jenniffer’s research employs various immunological methods to assess host humoral immune responses to HIV in subtype C chronically infected adults. Specifically, her goal is to define the relationship between HIV specific non-neutralizing antibodies and markers of disease progression and ultimately to characterize B cells that generate ‘protective’ antibodies. This knowledge will be valuable towards designing an antibody-based HIV vaccine.

Nicole Reddy

MASTERS STUDENT

Nicole Reddy completed her BSc degree in Microbial Biotechnology, majoring in Microbiology and Genetics, at the University of KwaZulu-Natal (UKZN) in 2013. She completed her Honours degree in Medical Microbiology at the Nelson R Mandela School of Medicine in 2014. While in her Honours year she demonstrated for the K-RITH mycobacteriophage course and during this time attended a talk by K-RITH investigator Thumbi Ndung’u. She was inspired by the ground-breaking research done by the Ndung’u Lab and applied to do a Masters degree through the lab. For Nicole’s Masters project she will be 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 K-RITH Postdoctoral Fellow Kavidha Reddy.

Nathan Kieswetter

MASTERS STUDENT

Nathan Kieswetter completed his BSc in Biological Science at the University of KwaZulu-Natal (UKZN) in 2013. During his third year he was introduced to TB research whilst attending K-RITH’s annual mycobacteriophage course. In 2014 he went on to complete his BSc Honours in Biological Science, graduating cum laude. His honours project looked at the optimisation of cryostorage and subsequent retrieval of economically important plant genetic material. He has since moved to K-RITH in the capacity of a masters student under K-RITH Research Associate Dr Emily Wong and K-RITH investigator Professor Thumbi Ndung’u. Nathan’s current masters research project is focussed on the development and optimisation of quantitative real time PCR assays to detect key antimicrobial peptides and mediators important in innate immune protection and control of M.tb infection in monocytes/macrophages. Further, his research aims to determine the effect of microbial products, HIV infection and associated cytokines on cellular expression of these molecules to better understand the mechanisms of innate protection during HIV/TB co-infection.

Kavidha Reddy

POSTDOCTORAL RESEARCH FELLOW

Kavidha Reddy hails from Durban and holds a BSc honours degree in Biomedical Science and an MSc in Molecular Biology from the University of KwaZulu-Natal (UKZN). Having grown up at the epicentre of the HIV epidemic and witnessing the disease’s devastating impact first hand, Kavidha quickly realised that her passion lay in scientific research, particularly in the study of HIV where she hopes to make a contribution in the struggle to find a cure for the HIV-1 subtype C epidemic in Southern Africa. Kavidha’s PhD focussed on the study of the host restriction factor, APOBEC3G, and its role in HIV-1 subtype C infection. She was a recipient of a Young Investigator Award from the International Aids Society and the French National Agency for Research on Aids. Kavidha’s postdoctoral work 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. She believes that an understanding of virus-host interactions and how cellular restriction factors target HIV-1 replication is critical as research in this area may inform vaccine design and provide a new avenue for future Aids therapies.

Daniel Muli Muema

POSTDOCTORAL RESEARCH FELLOW

BACKGROUND

Daniel Muli Muema grew up in Machakos, Kenya. He trained as a pharmacist at the University of Nairobi until 2007, and then worked briefly as a government pharmacist before joining the KEMRI-Wellcome Trust Research Programme.  In 2014, he completed PhD training at Open University UK in collaboration with University of Liverpool and KEMRI-Wellcome Trust Research Programme, studying the phenotypic and functional defects of B cells in HIV-infected children. His other work has been on immunological responses to pneumococcal vaccines and malaria. 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.

Bongiwe Xulu

RESEARCH LABORATORY TECHNOLOGIST 

Bongiwe Xulu was born and raised on the north coast of KwaZulu-Natal.  For her Masters degree in Biochemistry at UKZN, she worked on testing the selective cytotoxicity of hypoxoside (an isolate from African potato) and its prepared derivatives to MCF10A and MCF10A-NeoT cancer cell lines. Bongiwe is currently working as a laboratory technician under Dr Emily Wong, focussing 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.

Akeem Ngomu

PHD SCHOLAR

Ngomu Akeem Akilimali grew up in the Democratic Republic of Congo.  He immigrated to South Africa in 2002 and completed his undergraduate degree in 2008 at the UKZN School of Genetics and Biochemistry. He then completed a Masters in Medical Science with the HIV Pathogenesis Programme at UKZN in 2011. Akeem’s Masters research focussed on how the HIV-induced upregulation of Leukocyte Immunoglobulin (Ig)-Like Receptors is abrogated in individuals co-infected with Mycobacterium tuberculosis. Akeem is currently doing his PhD under the supervision of Professor Thumbi Ndung’u. His work focusses on the investigation of immune activation and pathogen-specific immune response in cryptococcal meningitis-associated immune reconstitution inflammatory syndrome (C-IRIS).

Selected Publications

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