Malcolm Whiteway, PhD

Education

PhD (University of Alberta)

Research interests

Our ongoing research investigates the medically important fungal pathogen Candida albicans, with the ultimate goal of identifying new treatment options for patients suffering from Candida infections. We use an array of genetic and genomic approaches to investigate pathways involved in various C. albicans functions. As part of these efforts we collaborated with various international research teams in the assembly and annotation of the C. albicans genome. We are now using genome-based tools such as transcriptional profiling and ChIP-chip analysis to investigate regulatory circuits in the pathogen. We have identified dramatic cases of transcriptional rewiring of central metabolic pathways, synchronized cells and established the transcriptional profile of the C. albicans cell cycle, and investigated the regulation of the fungal mating system. We are also screening an extensive library of conditional C. albicans mutants using various physiological and chemical treatments through the functional Genomics robotic facility at Concordia. This will allow us to explore, tailor, and understand the subtleties that make C. albicans a human pathogen.

Funding sources

NSERC, FQRNT, Genome Quebec, Canada Research Chairs

BIOL 511/BIOL 481, Structural Genomics
BIOL 261, Genetics

Zhen C, Wang L, Feng Y, Whiteway M, Hang S, Yu J, Lu H, Jiang Y. (2024) Ontionium bromide exhibits potent antifungal effects by blocking ergosterol plasma membrane localization and triggering cytotoxic autophagy in Candida albicans. Adv Sci (Weinh). 12:e2406473.

Li W, Feng Y, Feng Z, Wang L, Whiteway M, Lu H, Jiang Y. (2024) Pitavastatin calcium confers fungicidal properties to fluconazole by inhibiting ubiquinone biosynthesis and generating reactive oxygen species Antioxidants (Basel).13:667.

Dumeaux V, Massahi S, Bettauer V, Mottola A, Dukovny A, Khurdia SS, Costa ACBP, Omran RP, Simpson S, Xie JL, Whiteway M, Berman J, Hallett MT. (2023) Candida albicans exhibits heterogeneous and adaptive cytoprotective responses to antifungal compounds. Elife. 12:e81406

Shrivastava M, Kouyoumdjian GS, Kirbizakis E, Ruiz D, Henry M, Vincent AT, Sellam A, Whiteway M. The Adr1 transcription factor directs regulation of the ergosterol pathway and azole resistance in Candida albicans. (2023) mBio. 14:e0180723.

Bagley JA, Pyne ME, Exley K, Kevvai K, Wang Q, Whiteway M, Martin VJJ (2023) Genome sequencing of 15 acid tolerant yeasts. Microbiol Resour Announc.12. e0033723

Pyne, ME., Bagley JA., Narcross, L., Kevvai, K., Exley K., Wang Q., Whiteway, M., Martin       VJJ. (2023) Screening non-conventional yeasts for acid tolerance and engineering Pichia occidentalis for production of muconic acid. Nat. Commun. 14, 5294

Lu, H, Li, W., Whiteway, M., Wang, H., Zhu, S., Ji, Z., Feng, Y., Yan, L., Fang, T., Li, L., Ni, T., Zhang,X., Lv, Q., Ding, Z., Qiu, L., Zhang, D., Jiang YY (2023) A small molecule inhibitor of Erg251 makes fluconazole fungicidal by inhibiting the synthesis of the 14a-methysterols. mBio 14, e02639-22

Shahina, Z., Al Homsi, R., Price, JDW., Whiteway, M., Sultana, T., Dahms, TES. (2022) Rosemary essential oil and its components 1,8-cineole and α-pinene induce ROS-dependent lethality and ROS-independent virulence inhibition in Candida albicans PLoS One 17, e0277097

Bettauer, V., Costa, ACBP., Omran, RP., Massahi, S., Kirbizakis, E., Simpson, S., Dumeaux, V., Law, C., Whiteway, M., Hallett, MT. (2022). A deep learning approach to capture the essence of Candida albicans morphologies. Microbiology Spectrum 10, e01472-22

Feng, Y., Zhang, Y., Li, J., Omran, RP., Whiteway, M., Feng, J. (2022). Transcriptional Profiling of the Candida albicans Response to the DNA Damage Agent Methyl Methanesulfonate. IJMS 23. 7555-7575.

Li, L., Lu, H., Zhang, X., Whiteway, M., Wu, H., Tan, S., Zang, J., Tian, S., Zhen, C., Meng, X., Li, W., Zhang, D., Zhang, M., Jiang YY. (2022). Baicalein Acts against Candida albicans by Targeting Eno1 and Inhibiting Glycolysis. Microbiology Spectrum 10, e02085-22

Bean, BDM., Whiteway, M., Martin, VJJ. (2022). The MyLo CRISPR-Cas9 Toolkit: A Markerless Yeast Localization and Overexpression CRISPR-Cas9 Toolkit. G3 12, jkac154.

Bean, BDM., Mulvihill, CJ., Garge, RK., Boutz, DR., Rousseau, O., Floyd, BM., Cheney, W., Gardner, EC., Ellington, AD., Marcotte, EM., Gollihar, JD., Whiteway, M., Martin, VJJ. (2022). Functional expression of opioid receptors and other human GPCRs in yeast engineered to produce human sterols. Nat. Commun. 13, 2882.

Godoy P, Darlington PJ, Whiteway M. (2022) Genetic Screening of Candida albicans Inactivation Mutants Identifies New Genes Involved in Macrophage-Fungal Cell Interactions. Front. Microbiol 13, 833655

Omran, RP., Ramirez-Zavala, BR., Tebung, WA., Yao, S., Feng, J., Law, C., Dumeaux, V., Morschhauser, J., Whiteway, M. (2022). The zinc cluster transcription factor Rha1 is a positive filamentation regulator in Candida albicans. Genetics. 220, iyab155.

Rashid, S., Correia-Mesquita, TO., Godoy, P., Omran, RP., Whiteway, M. (2022). SAGA Complex Subunits in Candida albicans Differentially Regulate Filamentation, Invasiveness,

and Biofilm Formation. Frontiers in Cellular and Infection Microbiology. 12, 764711

Shrivastava, M., Feng, J., Coles, M., Clark, B., Islam, A., Dumeaux, V., Whiteway, M. (2021). Modulation of the complex regulatory network for methionine biosynthesis in fungi. Genetics. 217, iyaa049.

Costa, ACBP., Omran, RP., Law, C., Dumeaux, V., Whiteway, M. (2021). Signal-mediated localization of Candida albicans pheromone response pathway components. G3. 11, jkaa033.

Feng J, Islam A, Bean B, Feng J, Sparapani S, Shrivastava M, Goyal A, Omran, RP, Mallick J, Whiteway M. (2020) Hof1 plays a checkpoint-related role in MMS-induced DNA damage response in Candida albicans. Mol Biol Cell, 31, 348-359.

Feng J, Yao S, Dong Y, Hu J, Whiteway M, Feng J. (2020) Nucleotide excision repair protein Rad23 regulates cell virulence independent of Rad4 in Candida albicans mSphere 5, e00062-20

Xu H, Fang T, Omran RP, Whiteway M, Jiang L (2020) RNA sequencing reveals an additional Crz1-binding motif in promoters of its target genes in the human fungal pathogen Candida albicans. Cell Commun Signal. 18:1.

Costa ACBP, Omran RP, Correia-Mesquita TO, Dumeaux V, Whiteway M. (2019) Screening of Candida albicans GRACE library revealed a unique pattern of biofilm formation under repression of the essential gene ILS1.Sci Rep. 9: 9187.

Rastghalam G, Omran RP, Alizadeh M, Fulton D, Mallick J, Whiteway M. (2019) MAP Kinase Regulation of the Candida albicans Pheromone Pathway. mSphere. 4: e00598-18.

Sharmeen N, Sulea T, Whiteway M, Wu C. (2019) Adapter protein Ste50p directly modulates yeast MAPK signaling specificity through differential connections of its RA domain. Mol Biol Cell. 30: 794-807.

Polvi EJ, Veri AO, Liu Z, Hossain S, Hyde S, Kim SH, Tebbji F, Sellam A, Todd RT, Xie JL, Lin ZY, Wong CJ, Shapiro RS, Whiteway M, Robbins N, Gingras AC, Selmecki A, Cowen LE. (2019) Functional divergence of a global regulatory complex governing fungal filamentation. PLoS Genet. 15:e1007901.

Islam A, Tebbji F, Mallick J, Regan H, Dumeaux V, Omran RP, Whiteway M. (2018) Mms21: A Putative SUMO E3 Ligase in Candida albicans That Negatively Regulates Invasiveness and Filamentation, and Is Required for Genotoxic and Cellular Stress Response.

Genetics. 211: 579-595.

Xu H, Whiteway M, Jiang L. (2018) The tricarboxylic acid cycle, cell wall integrity pathway, cytokinesis and intracellular pH homeostasis are involved in the sensitivity of Candida albicans cells to high levels of extracellular calcium.  Genomics. S0888-7543(18)30307-0.

Shahina Z, El-Ganiny AM, Minion J, Whiteway M, Sultana T, Dahms TES. (2018) Cinnamomum zeylanicum bark essential oil induces cell wall remodelling and spindle defects in Candida albicans. Fungal biology and biotechnology 5, 3.

Veri AO, Miao Z, Shapiro RS, Tebbji F, O'Meara TR, Kim SH, Colazo J, Tan K, Vyas VK, Whiteway M, Robbins N, Wong KH, Cowen LE. (2018) Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space. PLoS Genetics 14, e1007270

Chen Y, Mallick J, Maqnas A, Sun Y, Choudhury BI, Cote P, Yan L, Ni TJ, Li Y, Zhang D, Rodríguez-Ortiz R, Lv QZ, Jiang YY, Whiteway M. (2018) Chemogenomic profiling of the fungal pathogen Candida albicans. Antimicrob Agents Chemother. 62, e02365

Tebung WA, Omran RP, Fulton DL, Morschhäuser J, Whiteway M. (2017) Put3 Positively Regulates Proline Utilization in Candida albicans. mSphere. 2, e00354-17.

Scaduto CM, Kabrawala S, Thomson GJ, Scheving W, Ly A, Anderson MZ, Whiteway M, Bennett RJ. (2017) Epigenetic control of pheromone MAPK signaling determines sexual fecundity in Candida albicans. Proc Natl Acad Sci U S A. 114, 13780-85.

Tebbji F, Chen Y, Sellam A, Whiteway M. (2017) The Genomic Landscape of the Fungus-Specific SWI/SNF Complex Subunit, Snf6, in Candida albicans. mSphere 2, e00497-17.

Regan H, Scaduto CM, Hirakawa MP, Gunsalus K, Correia-Mesquita TO, Sun Y, Chen Y, Kumamoto CA, Bennett RJ, Whiteway M. (2017) Negative regulation of filamentous growth in Candida albicans by Dig1p. Mol Microbiol. 105, 810-824.

Shekhar-Guturja T, Tebung WA, Mount H, Liu N, Köhler JR, Whiteway M, Cowen LE. Beauvericin Potentiates Azole Activity via Inhibition of Multidrug Efflux, Blocks Candida albicans Morphogenesis, and Is Effluxed via Yor1 and Circuitry Controlled by Zcf29. Antimicrob Agents Chemother. 60, 7468-7480.

Tebung, WA, Choudhury, BI, Tebbji, F, Morschhäuser, J, Whiteway, M. (2016) In the Saccharomycetaceae the Ppr1 zinc cluster transcription factor has been rewired from purine catabolism to pyrimidine biogenesis. Curr. Biol 26:1677-87.

Sun Y, Gadoury C, Hirakawa MP, Bennett RJ, Harcus D, Marcil A, Whiteway M. (2016) Deletion of a Yci1 Domain Protein of Candida albicans Allows Homothallic Mating in MTL Heterozygous Cells. mBio. 7, e00465-16.

Zhao Y, Yan H, Happeck R, Peiter-Volk T, Xu H, Zhang Y, Peiter E, van Oostende Triplet C, Whiteway M, Jiang L. (2016) The plasma membrane protein Rch1 is a negative regulator of cytosolic calcium homeostasis and positively regulated by the calcium/calcineurin signaling pathway in budding yeast. Eur J Cell Biol. 95, 164-74

Mallick J, Jansen G, Wu C, Whiteway M. (2016) SRYTH: A New Yeast Two-Hybrid Method. Methods Mol Biol. 1356, 31-41.

Yan L, Xiong J, Lu H, Lv QZ, Ma QY, Côte P, Whiteway M, Jiang YY (2015) The Role of Mms22p in DNA Damage Response in Candida albicans (2015) G3 (Bethesda). 5, 2567-78.