Martchenko M, Candille SI, Tang H, Cohen SN. Human genetic variation altering anthrax toxin sensitivity.
Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2972-7

Martchenko M, Jeong SY, Cohen SN. Heterodimeric integrin complexes containing beta1 integrin promote internalization and lethality of anthrax toxin.
Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15583-8

Martchenko M, Levitin A, Hogues H, Nantel A, and Whiteway M. Transcriptional rewiring of fungal galactose-metabolism circuitry.
Current Biology (Cell Press). 2007 Jun 19;(17):1-7

van Het Hoog M*, Rast TJ*, Martchenko M, Grindle S, Dignard D, Hogues H, Berriman M, Scherer S, Magee BB, Whiteway M, Chibana H, Nantel A, Magee PT.  Assembly of the Candida albicans genome into sixteen supercontigs aligned on the eight chromosomes.
Genome Biol. 2007 Apr 9;8(4):R52

Martchenko M, Levitin A, Whiteway M. Transcriptional activation domains of the Candida albicans Gcn4p and Gal4p homologs.
Eukaryot Cell. 2007 Feb;6(2):291-301

Braun BR, van Het Hoog M, d'Enfert C, Martchenko M, Dungan J, Kuo A, Inglis DO, Uhl MA, Hogues H, Berriman M, Lorenz M, Levitin A, Oberholzer U, Bachewich C, Harcus D, Marcil A, Dignard D, Iouk T, Zito R, Frangeul L, Tekaia F, Rutherford K, Wang E, Munro CA, Bates S, Gow NA, Hoyer LL, Köhler G, Morschhäuser J, Newport G, Znaidi S, Raymond M, Turcotte B, Sherlock G, Costanzo M, Ihmels J, Berman J, Sanglard D, Agabian N, Mitchell AP, Johnson AD, Whiteway M, Nantel A. A human-curated annotation of the Candida albicans genome.
PLoS Genet. 2005 Jul;1(1):36-57

RESEARCH SYNOPSIS:

Dr. Martchenko's prior work in the host-pathogen field has focused on the discoveries of virulence strategies of human pathogens Candida albicans and Bacillus anthracis (anthrax), understanding of how they exploit human hosts, and evaluation of therapeutic intervention points. He found that human genetic variation within genes exploited by pathogens alters the sensitivity of hosts to the adverse effects of infectious microbes.

By combining advanced genetic, biochemical, evolutionary, and bioinformatics approaches, Dr. Martchenko's ongoing research investigates pathogenic strategies of medically important fungal pathogen Candida albicans, and toxins of bacterial pathogen Bacillus anthracis, with the ultimate aim of discovering and evaluating approaches that will allow effective therapeutic interventions. His research specializes in advancing our understanding of bacterial and fungal pathogens, which is important from medical, veterinary, academic, and bio-defense points of view.

CURRENT RESEARCH PROJECTS:

Identification of C. albicans and host genes necessary for the evasion of phagocytosis:

Candida evades and escapes from host innate immunity, and often causes irritating and recurrent infections. While C. albicans evades phagocytosis, little is known about the molecular basis of this virulence mechanism, in part because of the lack of simple, genetically tractable phagocytosis models to facilitate en masse identification of virulence determinants. The research in Dr. Martchenko lab is aimed at developing a high-throughput assay to monitor levels of resistance of C. albicans and the closely related avirulent Saccharomyces cerevisiae to host phagocytosis. Using this assay, fungal mutants are screened, and Candida genes that decrease or increase C. albicans resistance to phagocytosis are identified. Fungal genes, inactivation of which leads to the increased sensitivity to phagocytosis, represent potential targets for the development of anti-fungal treatments.

To facilitate the development of anti-fungal countermeasures, Dr. Martchenko lab research has also taken an alternative and novel approach to identify and target host genes exploited by C. albicans during the evasion of phagocytosis. Finding host genes exploited by Candida and inhibiting them could be used as another anti-fungal approach for treating Candida infections. Based on the previous work it is expected that the inhibition of some of the identified host genes will decrease the pathogenicity of multiple fungal pathogens, such as Aspergillus fumigatus and Cryptococcus neoformans.

Identification of human genetic variation that affects anthrax pathogenicity:

Dr. Martchenko's recent work shows that human susceptibility to anthrax toxin varies greatly among individuals, and that it is a heritable genetic trait, determined by human genetic variation within genes exploited by pathogens. Dr. Martchenko lab identifies genetic variation within human anthrax toxin receptor that affects its function and results in altered ability of anthrax toxin to kill the host cell. The goal of this study is to offer a useful strategy for elucidating effects of genetic variation on anthrax susceptibility.

FUTURE RESEARCH INTERESTS:

Dr. Martchenko lab is interested in screening libraries of small molecules for their ability to inhibit the growth of Candida albicans in host serum.

"Methods and Compositions for Preventing and Treating an Anthrax Toxin Mediated Condition in a Subject", Mikhail Martchenko, Sun-Young Jeong, and Stanley N. Cohen. U.S. Provisional Application Serial No. 61/523,693. Filing date August 15, 2011.