Prof L Birkholtz

Office:  7-7 Agriculture Building

Tel: 012-420-2479

Fax: 012-362-5302

E-maillynmarie.birkholtz [at] up.ac.za

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Malaria Parasite Molecular Laboratory

DST/NRF South African Research Chair (SARChI) in Sustainable Malaria Control

UP ISMC


Profile

Lyn-Marie Birkholtz is a full professor in Biochemistry and director of a Tier 1 DST/NRF South African Research Chair (SARChI) in Sustainable Malaria Control. She leads the Parasite Cluster within the UP Institute for Sustainable Malaria Control. She is an elected member of the Academy of Science of South Africa. She is trained as Geneticist and Biochemist and received her PhD in Biochemistry at the University of Pretoria, followed by postdoctoral fellowships in Germany and the USA. Prof Birkholtz is a NRF B2-rated scientist and was recognised by UP recognised as Exceptional Young Researcher in 2010 and 2013, and as Exceptional Academic Achiever for 2019-2021. She received the Vice Chancellor’s Exceptional Supervisor Award in 2018 and the NSTF Science Communication Award in 2018.

Current research interests

Broad areas: Infectious diseases, parasitology, therapeutics, medicinal biochemistry

Specifics: As principal investigator of the Malaria Parasitology Molecular Laboratory (M2PL), I have a keen interest in the fundamental processes driving parasitism and how this sustains global health challenges, of which malaria is still arguably devastating. However, I feel a social responsibility to directly translate my research outcomes into meaningful and tangible health innovations, particularly to discover new antimalarial drugs. As such, I find it fascinating and rewarding to work at the interface between parasite biology and drug discovery and use new biological insights as a catalyst for drug discovery. However, I cannot do so without an in-depth understanding of the essential processes driving survival and pathogenesis of malaria parasites. This is a substantial research challenge, and one I approach from a systems level. I therefore generate global descriptors of asexual parasite proliferation and gametocyte differentiation, to tease apart the molecular regulators involved and provide meaningful information on essential druggable processes. I particularly focus on the pathogenic processes driving proliferation and differentiation of malaria parasites to deliver drugs able to target both these. In line with international endeavours focused on achieving malaria elimination, my research uses high-content biological information of malaria parasites to support sustained discovery of malaria control chemotherapies to contribute to the global ‘Malaria Eradication Agenda’. My research programme is therefore built on three integrated pillars: 1) understanding parasite biology associated with pathogenesis (proliferation and differentiation), 2) antimalarial drug discovery for malaria elimination endeavours and 3) understanding host-parasite interactions that drive sustained malaria transmission.

I am passionate about training of the next generation of young scientist in the cutting edge technologies used in our programme. To date, 19 PhD & 28 MSc has been completed under my (co)-supervision, with several graduates successfully appointed in international fellowships.

Recent publications

  1. Moyo P, Shamburger W, van der Watt ME, Reader J, de Sousa ACC, Egan TJ, Maharaj VJ, Bringmann G, Birkholtz LM. (2020) Naphthylisoquinoline alkaloids, validated as hit multistage antiplasmodial natural products. Int J Parasitol Drugs Drug Resist. May 24;13:51-58. doi: 10.1016/j.ijpddr.2020.05.003. IF: 3.009
  2. Raman, J, Gast, L, Balawanth, R, Tessema, S, Brooke, B, Maharaj, R, Munhenga, G, Tshikae, P, Lakan, V, Mwamba, T, Makowa, H, Sangweni, L, Mkhabela, M, Zondo, N, Mohulatsi, E, Nyawo, Z, Ngxongo, S, Msimang, S, Dagata, N, Greenhouse, B, Birkholtz, L, Shirreff, G, Graffy, R, Qwabe, B and D Moonasar. (2020) High levels of imported asymptomatic malaria but limited local transmission in KwaZulu‑Natal, a South African malaria‑endemic province nearing malaria Elimination. 2020, Malaria Journal, 19:152; https://doi.org/10.1186/s12936-020-03227-3 IF: 3.109
  3. Coetzee, N., Von Gruning, H., Opperman, D., van der Watt, M., Reader, J., Birkholtz L. (2020) Epigenetic inhibitors target multiple stages of Plasmodium falciparum parasites. Scientific Reports.. 10:2355, DOI: 10.1038/s41598-020-59298-4. IF: 4.06
  4. Wong, H.N., Padín-Irizarry, V., van der Watt, M.,  Reader, J., Liebenberg, W., Wiesner, L., Smith, P., Eribez, K., Winzeler, E.K, Kyle, D.E., Birkholtz, L., Coertzen, D.,  Haynes, R.K. (2020) Optimal 10-aminoartemisinins with potent transmission-blocking capabilities for new ACTs – activities against blood stage P. falciparum including PfKI3 C580Y mutants and liver stage P. berghei parasites. Frontiers in Chemistry, section Medicinal and Pharmaceutical Chemistry, Jan 10;7:901. doi: 10.3389/fchem.2019.00901.  IF 3.994
  5. Duvenhage J, Ebenhan T, Garny S, Hernández González I, Leyva Montaña R, Price R, Birkholtz LM, Zeevaart JR. (2020) Molecular Imaging of a Zirconium-89 Labeled Antibody Targeting Plasmodium falciparum-Infected Human Erythrocytes. Molecular Imaging Biol., Feb;22(1):115-123. doi: 10.1007/s11307-019-01360-3. IF: 3.341
  6. Ahenkorah, S., Coertzen, D., Tong, J.X., Fridianto, K.T., Wittlin, S., Birkholtz, L., Tan, K., Lam, Y., Go, M.L.,  Haynes, R.K. Antimalarial N1,N3-dialkyldioxonaphthoimidazoliums: Synthesis, biological activity and structure-activity relationships. ACS Medicinal Chemistry letters. 2019 Dec 11;11(1):49-55. doi: 10.1021/acsmedchemlett.9b00457. eCollection 2020 Jan 9. IF 3.737
  7. van Biljon R, van Wyk R, Painter HJ, Orchard L, Reader J, Niemand J, Llinás M, Birkholtz L.  (2019). Hierarchical transcriptional control regulates Plasmodium falciparum sexual differentiation. BMC Genomics, Dec 3;20(1):920.DOI: 10.1186/s12864-019-6322-9, IF 3.501
  8. Duvenhage J, Ebenhan T, Garny S, Hernández González I, Leyva Montaña R, Price R, Birkholtz LM, Zeevaart JR. (2019) Molecular Imaging of a Zirconium-89 Labeled Antibody Targeting Plasmodium falciparum-Infected Human Erythrocytes. Mol Imaging Biol. Apr 19. doi: 10.1007/s11307-019-01360-3. IF 3.466
  9. Awandu SS, Raman J, Bousema T, Birkholtz L. (2019) Ultra-low-density Plasmodium falciparum infections in African settings. Clinical Infectious Diseases, Feb 15. pii: ciz147.cix147, doi.org/10.1093/cid/ciz147. IF 9.117
  10. Moyo P, Kunyane P, Selepe MA, Eloff JN, Niemand J, Louw AI, Maharaj VJ, Birkholtz LM (2019) Bioassay-guided isolation and identification of gametocytocidal compounds from Artemisia afra (Asteraceae). Malar J. Mar 8;18(1):65. doi: 10.1186/s12936-019-2694-1. IF 3.109
  11. Kumar M, Okombo J, Mambwe D, Taylor D, Lawrence N, Reader J, van der Watt M, Fontinha D, Sanches-Vaz M, Bezuidenhout B, Lauterbach S, Liebenberg D, Birkholtz L, Coetzer TL, Prudêncio M, Egan T, Wittlin S, Kelly Chibale (2019) Multistage Antiplasmodium Activity of Astemizole Analogues and Inhibition of Hemozoin Formation as a Contributor to Their Mode of Action.  ACS Infect. Dis. Feb 8;5(2):303-315.DOI: 10.1021/acsinfecdis.8b00272, http://hdl.handle.net/2263/68201. IF 4.991
  12. Mayoka G, Njoroge M, Okombo J, Gibhard L, Sanches-Vaz M, Fontinha D, Birkholtz L, Reader J, van der Watt M, Coetzer TL, Lauterbach S, Churchyard A, Bezuidenhout B, Egan T, Yeates C, Wittlin S, Prudêncio M, and Kelly Chibale (2019) Structure-activity relationship studies and Plasmodium life cycle profiling identifies pan-active N-aryl-3-trifluoromethyl pyrido[1,2-a]benzimidazoles which are efficacious in an in vivo mouse model of malaria. J. Med. Chem., Jan 24;62(2):1022-1035, DOI: 10.1021/acs.jmedchem.8b01769. IF 6.054
  13. Van Biljon R, Niemand J, van Wyk R, Clark K, Verlinden B, Abrie C, von Gruning H, Smidt W, Smit A, Reader J, Painter H, Llinas M, Doerig C, and L Birkholtz (2018) Inducing controlled cell cycle arrest and re-entry during aseuxal proliferation of Plasmodium falciparum parasites. Scientific Reports, 8:16581, doi:10.1038/s41598-018-34964-w (IF 4.609).
  14. Beteck R, Seldon R, Coertzen D, van der Watt M, Reader J, Mackenzie J, Lampbreacht D, Abraham M, Eribez K, Muller J, Rui F, Zhu G, de Grano R, Williams I, Smit F, Steyn A, Winzeler E, Hemphill A, Birkholtz L, Warner D, N’da D, Haynes R (2018). Accessible and distinct decoquinate derivatives highly active against M. tuberculosis and apicomplexan parasites. Comms. Chem, 1(62) DOI: 10.1038/s42004-018-0062-7. IF 6.416
  15. Brunschwig C, Lawrence M, Taylor D, Abay E, Njoroge M, Basarab G, Le Manach C, Paquet T, Gonzàlez Cabrera D, Nchinda A, de Kock C, Wiesner L, Denti P, Waterson D, Blasco B, Leroy D, Witty M, Donini C, Duffy J, Wittlin S, White K, Charman S, Jiménez-Díaz M, Angulo-Barturen I, Herreros E, Gamo F, Rochford R, Mancama D, Coetzer T, van der Watt M, Reader J, Birkholtz L, Marsh K, Solapure S, Vanaerschot M, Fidock D, Fish P, Siegl P, Smith D, Wirjanata G, Noviyanti R, Price R, Marfurt J, Silue K, Street L, and K Chibale. (2018) UCT943, a next generation Plasmodium falciparum PI4K inhibitor preclinical candidate for the treatment of malaria. Antimicrobl. Agents Chemotherapy. Aug 27;62(9). pii: e00012-18, doi: 10.1128/AAC.00012-18 (IF 4.476)
  16. Coertzen D, Reader J, van der Watt M, Nondaba SH, Gibhard L, Wiesner L, Smith P, D’Alessandro S, Taramelli D, Wong H. N, du Preez J. L., Wu R. W. K, Birkholtz L,# R, K. Haynes# (2018) Artemisone and artemiside - potent pan-reactive antimalarial agents that also synergize redox imbalance in P. falciparum transmissible gametocyte stages. Antimicrobl. Agents Chemotherapy. August 2018, 65:8, e02214-17. doi: 10.1128/AAC.02214-17 (IF 4.476) (http://hdl.handle.net/2263/66344)
  17. Awandu S. S., Raman J., Makhanthisa T. I., Kruger P., Frean J., Bousema T., Niemand J, Birkholtz L. (2018) Understanding human genetic factors influencing primaquine safety and efficacy to guide primaquine roll-out in a pre-elimination setting in southern Africa. Malaria J. 17:120 (IF 3.08)
  18. Van der Watt M, Reader J, Churchyard A, Nondaba SH, Lauterbach, SB, Niemand J, Abayomi S, van Biljon R, Connacher JI, van Wyk RDJ, Le Manach C, Paquet T, Gonzales Cabrera D, Brunschwig C, Theron A, Lozano-Arias S, Rodrigues JFI, Herreros E, Leroy D, Duffy J, Street LJ, Chibale K, Mancama D, Coetzer TL, Birkholtz L. (2018) Potent Plasmodium falciparum gametocytocidal compounds identified by exploring the kinase inhibitor chemical space for dual active antimalarials. J Antimicrob Chemotherapy, May 1;73(5):1279-1290. doi: 10.1093/jac/dky008 (IF: 5.313)
  19. Morake M, Coertzen D, Ngwane A, Wentzel JF, Wong HN, Smit FJ, Birkholtz L, Petersen, R, Baker B, Wiid I, N’Da D, Haynes RK. (2018) Preliminary Evaluation of Artemisinin - Cholesterol Conjugates as Potential Drugs for Treatment of Intractable Forms of Malaria and Tuberculosis. ChemMedChem. 2018 Jan 8;13(1):67-77. doi: 10.1002/cmdc.201700579. (IF 3.225)
  20. de Lange C, Coertzen D, Smit FJ, Wentzel JF, Wong HN, Birkholtz LM, Haynes RK, N'Da DD. (2018) Synthesis, antimalarial activities and cytotoxicities of amino-artemisinin-ferrocene derivatives. Bioorg Med Chem Lett. 28(3), pp. 3161-3163. https://doi.org/10.1016/j.bmcl.2018.08.037. (IF 2.42)
  21. de Lange C, Coertzen D, Smit FJ, Wentzel JF, Wong HN, Birkholtz LM, Haynes RK, N'Da DD. (2018) Synthesis, in vitro antimalarial activities and cytotoxicities of amino-artemisinin-ferrocene derivatives. Bioorg Med Chem Lett. 28(3), pp. 289-292. doi: 10.1016/j.bmcl.2017.12.057. (IF 2.42)
Published by Annel Smit

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