MB, ChB, Medicine and Surgery: University of Ghana Medical School, Accra, Ghana (1998)

MPhil, Microbiology: University of Ghana, Accra, Ghana
(2003)

Postgraduate Diploma in Statistics, ISSER, University of Ghana

PhD, Biomedical Sciences: University of New Mexico, Albuquerque, NM 
(2007)

Residency, Internal Medicine: Barnes-Jewish Hospital/Washington University, St. Louis, MO 
(2010)

Fellowship, Infectious Diseases: Washington University School of Medicine, St. Louis, MO 
(2014) 

Infectious Diseases (American Board of Internal Medicine)

Internal Medicine (American Board of Internal Medicine)

Medical License – State of Missouri, USA

Medical License –Medical and Dental Council, Ghana 

My research interests are in HIV latency and reservoir maintenance. An important obstacle to the cure of HIV is viral replication in long lived, quiescent immune cells such as macrophages, dendritic cells and resting T cells. These cells serve as sources of viral production once medications are discontinued, making life-long therapy a necessity. In addition, slow or inefficient replication makes the virus less susceptible to current antiretrovirals in these cell types. My research laboratories at the Noguchi Memorial Institute for Medical Research and Washington University are focused on (i) characterization of factors that control HIV replication in macrophages, dendritic and resting T cells, (ii) identification of cellular factors and small molecules required for HIV reactivation in latently infected cells and (iii) determination of patient perspectives on HIV cure research. 

 

(1) Cellular factors that control HIV replication in macrophages

We are looking at how the interplay between cyclin L2, DYRK1A and SAMHD1 control HIV replication in macrophages. (Kyei et al,

Cell Host Microbe, 2015, Kisaka et al, J. Virol, 2020).  This project aims to:

1. Define the mechanism by which the kinase DYRK1A regulates cyclin L2 in macrophages

2. Determine how cyclin L2 controls SAMHD1 in macrophages during HIV infection

 

(2) The role of SF3B1 in HIV latency and reactivation

We discovered the splicing factor SF3B1 as critical for HIV transcription and reactivation from latency. This project aims to:

1. Define the molecular domains of Tat-SF3B1 interactions required for viral transcription. 

2. Develop an assay to identify small molecules that block Tat-SF3B1 interactions to control HIV transcription

 

(3) Screening epigenetic compounds and African Herbal Extracts for HIV reactivation. The aims of this project are: 

1. To fully characterize a cohort of HIV patients and evaluate their knowledge and attitude towards participation in HIV cure research.

2. To screen a panel of 150 epigenetic modifying compounds and African herbal extracts for ability to reactivate HIV from latency in a cell line and primary cell model of latency.

3. To evaluate top 10 lead compounds in resting CD4 T cells isolated from patients suppressed on ART for more than 6 months.

4. To assemble a well-characterized HIV patient’s biobank to serve as a repository of samples for future research and student training.

(4) Impact of tuberculosis on the HIV reservoir 

Tuberculosis produces antigens that can stimulate T cells, which can result in proliferation and alter the response of the HIV reservoir to latency reversing agents. Persistent stimulation could also result in T cell exhaustion. However, the impact of TB on the HIV reservoir has not been investigated. This project aims to:

1. Determine the activation and exhaustion status of T cells in virologically suppressed patients infected with HIV/TB or HIV alone.

2.  Determine the size of the HIV reservoir in HIV only and HIV/TB co-infected patients.

3.  Determine the response of resting CD4+ T cells to latency reversing agents in co-infected patients.

Funding: EDCTP, NIH

1. Javan K. Kisaka, Lee Ratner, George B. Kyei. The dual specificity kinase DYRK1A modulates the levels of cyclin L2 to control HIV replication in macrophages. J. Virol. doi:10.1128/JVI.01583-19, 2020. 

2. Judge PT, Sesti EL, Price LE, Albert BJ, Alaniva N, Saliba EP, Halbritter T, Sigurdsson ST, Kyei GB, Barnes AB. Dynamic Nuclear Polarization With Electron Decoupling in Intact Human Cells and Cell Lysates. J Phys Chem B. 2020 

3. Patrick T Judge; Erika L Sesti; Nicholas Alaniva; Edward P Saliba; Lauren E Price; Chukun Gao; Thomas Halbritter; Snorri T Sigurdsson; George B Kyei and Alexander Barnes. Characterization of Frequency-chirped Dynamic Nuclear Polarization in Rotating Solids. J Magn Reson. doi: 10.1016/j.jmr.2020.106702.

4. Sarah A Overall, Lauren E Price, Brice J Albert, Chukun Gao, Nicholas Alaniva, Patrick T Judge, Erika L Sesti, Paul A Wender, George B Kyei, Alexander B Barnes. In Situ Detection of Endogenous HIV Activation by Dynamic Nuclear Polarization NMR and Flow Cytometry. Int J Mol Sci 2020 Jun 30;21(13):E4649. doi: 10.3390/ijms21134649.

 

5. Nicholas Ekow Thomford, Doreen Mhandire, Collet Dandara, George B. Kyei. Promoting Undetectable equals Untransmittable in sub-Saharan Africa: Implication for clinical practice and ART adherence. Int J. of Env Research and Public Health. 2020.  In Press. 

6. Beverly Egyir, Noah Obeng-Nkrumah, George B. Kyei. COVID-19 Pandemic and Antimicrobial Resistance: Another Call to Strengthen Laboratory Diagnostic Capacity in Africa. African J of Laboratory medicine. In Press. 

 

7. George Boateng Kyei, Shanshan Meng , Rashmi Ramani , Austin Niu , Chandraiah Lagisetti, Thomas R Webb , Lee Ratner. Splicing factor 3B subunit 1 interacts with HIV Tat and plays a role in viral transcription and reactivation from latency. mBio. 2018 Nov 6;9(6). pii: e01423-18.

8. Webster Heffern, Austin Niu, Rashmi Ramani, Garland Marshall, and George B. Kyei. Identification of isoform-selective hydroxamic acid derivatives that potently reactivate HIV from latency. J Virus Erad. 2019 Apr 1;5(2):84-91

9. Brice J. Albert, Austin Niu, Rashmi Ramani, Garland R. Marshall, Paul A. Wender, Robert M. Williams, Lee Ratner, Alexander B. Barnes & George B. Kyei. Combinations of isoform-targeted histone deacetylase inhibitors and bryostatin analogues display remarkable potency to activate latent HIV without global T-cell activation. Sci Rep. 2017 Aug 7;7(1):7456. PMID:28785069

10. George B Kyei, Xiaogang Cheng, Rashmi Ramani, Lee Ratner. Cyclin L2 is a critical HIV dependency factor in macrophages that controls SAMHD1 abundance. Cell Host Microbe. 2015. PMID: 25532805

 11. Ponpuak M, Davis AS, Roberts EA, Delgado MA, Dinkins C, Zhao Z, Virgin HW 4th, Kyei GB, Johansen T, Vergne I, Deretic V. Delivery of cytosolic components by autophagic adaptor protein p62 endows autophagosomes with unique antimicrobial properties. Immunity. 2010 Mar 26;32(3):329-41. PMID: 20206555

 12. George B. Kyei, Christina Dinkins, Alexander S. Davis, Esteban Roberts, Sudha B. Singh, Chunsheng Dong, Li Wu, Eiki Kominami, Takashi Ueno, Akitsugu Yamamoto, Maurizio Federico, Antonito Panganiban, Isabelle Vergne, and Vojo Deretic. Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. J. Cell Biol. 2009, Jul 186 (2) 255–268. PMID: 19635843.