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Professor Valerie Mizrahi PhD(UCT) OMS MASSAf FRSSAf FAAM Fellow of UCT

MRC/NHLS/UCT Molecular Mycobacteriology Research Unit

DST/NRF Centre of Excellence for Biomedical TB Research

Valerie Mizrahi

Director and Full Member, Institute of Infectious Disease and Molecular Medicine; Director, SAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit (MMRU) which constitutes the UCT node of the DST/NRF Centre of Excellence for Biomedical TB Research (CBTBR); Division of Medical Microbiology, Department of Pathology, Faculty of Health Sciences, University of Cape Town; former Senior International Research Scholar, Howard Hughes Medical Institute, USA (to October 2017).

Received the L'Oréal-UNESCO Award for Women in Science (2000); the Gold Medal from the South African Society for Biochemistry and Molecular Biology for her contributions to the field (2006); the Department of Science and Technology's Distinguished Woman Scientist Award (2006); named to the Order of Mapungubwe (2007); awarded the Institut de France's Christophe Mérieux Prize for her work in tuberculosis research (2013), and the Platinum Medal of the SAMRC for lifetime contributions to medical research in South Africa (2017).

Research in the MMRU is focused on aspects of mycobacterial physiology and metabolism of relevance to tuberculosis drug discovery, drug resistance, mycobacterial persistence and tuberculosis transmission. Currently, the Unit is actively involved in studying mechanisms of DNA metabolism, nucleotide metabolism, and cofactor metabolism in Mycobacterium tuberculosis, particularly as they apply to TB drug discovery. As a Unit that receives funding through two major grants from the South African government, research capacity development forms a key focus of the MMRU’s work.

The MMRU comprises senior scientists, early-career researchers, post-doctoral fellows, and PhD and MSc students, and also participates in several major TB drug discovery consortia funded by grants from the Bill & Melinda Gates Foundation under the TB Drug Accelerator program (SHORTEN-TB) and the SHIP programme of the SAMRC.


Selected publications:

Warner, D.F., Ndwandwe, D.E., Abrahams, G.L., Kana, B.D., Venclovas, Č., and Mizrahi, V. 2010. Essential roles for imuA’ and imuB-encoded accessory factors in DnaE2-dependent mutagenesis in mycobacteria. Proc. Natl. Acad. Sci. USA 107:13093-13098.

Abrahams, G.L., Kumar, A., Savvi, S., Hung, A.W., Wen, S., Abell, C.A., Barry, C.E. III, Sherman, D.R., Boshoff, H.I.M, and Mizrahi, V. 2012. Pathway-selective sensitization of Mycobacterium tuberculosis for target-based whole-cell screening. Chemistry & Biology 19:844-854.

Warner D.F., Evans, J.C., and Mizrahi, V. 2014. Nucleotide metabolism and DNA replication. In: Molecular Genetics of the Mycobacteria, 2nd Edition (Hatfull, G.F. & Jacobs, W.R., Jr., eds). ASM Press, Washington, ch. 30, pg. 635-656. doi: 10.1128/microbiolspec.MGM2-001-2013

Warner, D.F. and Mizrahi, V. 2014. Translation of genomics research into control of tuberculosis: lessons learned and future prospects. Genome Biol. 15:514. doi:10.1186/s13059-014-0514-z

Warner, D.F., Koch, A., and Mizrahi, V. 2015. Diversity and disease pathogenesis in Mycobacterium tuberculosisTrends Microbiol23:14-21. doi: 10.1016/j.tim.2014.10.005.

Singh, V., Brecik, M., Mukherjee, R., Evans, J.C., Svetlíková, S., Blaško, J., Blackburn, J., Warner, D.F., Mikušová, K. and Mizrahi, V. 2015. The complex mechanism of antimycobacterial action of 5-fluorouracil. Chem. Biol. 22:1-13.

Evans JC, Trujillo C, Wang Z, Eoh H, Ehrt S, Schnappinger D, Boshoff HIM, Rhee KY, Barry CE, Mizrahi V. 2016. Validation of CoaBC as a bactericidal target in the coenzyme a pathway of Mycobacterium tuberculosisACS Infectious Diseases 2(12):958-968.

Singh V, Mizrahi V. Identification and validation of novel drug targets in Mycobacterium tuberculosis. 2016. Drug Discovery Today22(3):503-509.

Singh, V., Donini, S., Pacitto, A., Sala, C., Hartkoorn, R.C., Dhar, N., Keri, G., Ascher, D.B., Mondésert, G., Vocat, A., Lupien, A., Sommer, R., Vermet, H., Lagrange, S., Buechler, J., Warner, D.F., McKinney, J.D., Pato, J., Cole, S.T., Blundell, T.L., Rizzi, M., and Mizrahi, V. The inosine monophosphate dehydrogenase, GuaB2, is a vulnerable new bactericidal drug target for tuberculosis. ACS Infect. Dis. 2017; 3:5-17. DOI: 10.1021/acsinfecdis.6b00102. PMCID# PMC5241705

Singh, V., Dhar, N., Pato, J., Kolly, G.S., Korduláková, J., Forbák, M., Evans, J.C., Szekely, R.E., Rybnicker, J.L., Svetlíková, Z., Zemanová, J., Santi, I., Signorino-Gelo, F., Rodrigues L., Vocat, A., Covarrubias, A.S., Rengifo, M.G., Johnsson, K., Mowbray, S., Buechler, J., Delorme, V., Brodin, P., Knott, G.W., Ainsa, J., Warner, D.F., Keri, G., Mikušová, K., McKinney, J.D., Cole, S.T.*, Mizrahi, V.* and Hartkoorn, R.C.* Identification of Aminopyrimidine-Sulfonamides as potent modulators of Wag31-mediated cell elongation in mycobacteria. Mol. Microbiol. 2017; 103:13-25. DOI: 10.1111/mmi.13535 [*Joint senior authors]

Evans, J., and Mizrahi, V. Priming the tuberculosis drug pipeline: new antimycobacterial targets and agents. Curr. Opin. Microbiol. 2018; 45:39-46

Koch, A., Cox, H., and Mizrahi, V. 2018. Drug resistant TB: Mechanisms of resistance and implications for diagnosis and disease management. Curr. Opin. Pharmacol. 42:7-15. https://doi.org/10.1016/j.coph.2018.05.013


Contact details:

Room 3.01, Wolfson Pavilion
Anzio Road
UCT Faculty of Health Sciences
Observatory 7925
Cape Town, South Africa

Tel:  +27 21 4066098
Fax: +27 21 4066068

email: valerie.mizrahi@uct.ac.za

 

Related sites:

www.medmicro.uct.ac.za

www.mrc.ac.za/mycobacteriology/mycobacteriology.htm

www.tuberculosis.org.za

 


Members of the MMRU:

Digby Warner

Deputy Director, MMRU

Joanna Evans

Research Officer

Melissa Chengalroyen

Research Officer

Anastasia Koch

Junior Research Fellow

Gabriel Mashabela

Postdoctoral fellow

Saber Anoosheh

Postdoctoral fellow

Sophia Gessner

Postdoctoral fellow

Charles Omollo

Postdoctoral fellow

Pooja Agarwal

Postdoctoral fellow

Mandy Mason

Postdoctoral fellow

Ryan Dinkele

PhD (Medical Microbiology)

Irene Gobe

PhD (Medical Microbiology)

Terry Kipkorir

PhD (Medical Microbiology)

Zela Martin

PhD (Medical Microbiology)

Rendani Mbau

PhD (Medical Microbiology)

Michael Reiche

PhD (Medical Microbiology)

Bianca Masuku

PhD (Medical Microbiology)

Timothy de Wet

PhD (Medical Microbiology)

Caitlin Taylor

MSc (Medical Microbiology)

Lucas Raphela

MSc (Medical Microbiology)

Audrey Jordaan

Lab Technologist

Sasha-Lee Lynch

Lab Technologist

Lameeza Jakoet

Administrative Assistant

 


Collaborations:

Dr. Clifton E. Barry III, NIAID, NIH, USA

Dr. Helena I. Boshoff, NIAID, NIH, USA

Prof. Paul Wyatt & Dr. Simon Green, Drug Discovery Unit, University of Dundee

Prof. Rolf Müller & Dr. Jennifer Hermann, Helmholtz Institute for Pharmaceutical Research, Saarland

Dr. David Olsen & Katherine Young, Merck Research Laboratories, USA

Prof. Deborah Hung, Broad Institute of MIT & Harvard

Prof. Menico Rizzi, Università degli Studi del Piemonte Orientale, Italy

Dr. Janos Pato, Vichem, Hungary

Prof. Tom Blundell, Cambridge University, UK

Dr. David Ascher, Cambridge University

Prof. Lizbeth Hedstrom, Brandeis University

Prof Erick Strauss, Stellenbosch University

Dr Vinayak Singh, UCT

Emer. Prof. Siamon Gordon, University of Oxford

Dr. Fernando Martinez Estrada, University of Surrey