Immunology & Infectious Diseases

Stephen Zucker

Manoocher Soleimani, MD

Int Med-Nephrol & Hypertension

Professor

Director Division of Nep

Research Summary

Aspergillus fumigatus is an environmental mould that propagates itself by the release into the air of high concentrations of conidia (spores), which are unavoidably inhaled. Patients who are immunosuppressed, such as cancer or transplant patients, are at increased risk for infection with these conidia, and the prognosis for invasive infections is very poor. Our lab is interested in how A. fumigatus balances its biosynthetic and degradative needs to optimize growth in the host, with the goal of developing new antifungal therapies that tip the balance in favor of degradation and fungal death. As a major component of the biomass in a self-heating compost pile, A. fumigatus has evolved thermotolerant biosynthetic activities that support rapid growth at 37oC. We have shown that one of these activities involves CgrA, a ribosome biogenesis protein. The objective of the lab is to further understand how CgrA promotes thermotolerance, with the long-term goal of identifying new strategies to disrupt the growth of the organism at 37oC.

We are also interested in mechanisms that regulate fungal programmed cell death (PCD). PCD has been divided into two major categories based on the effectors involved: caspase-dependent PCD (type I) and autophagy-dependent PCD (type II). Comparisons between mammalian and fungal genomes suggest that both of these pathways exist in lower eukaryotes. However, little is understood about their nature and function in filamentous fungi. The goal of the lab is to characterize the molecules involved in these pathways, and to understand their contribution to the growth and virulence of A. fumigatus.

Recent Publications

Li HC, Collier JH, Shawki A, Rudra JS, Li EY, Mackenzie B, Soleimani M.Sequence- or position-specific mutations in the carboxyl-terminal FL motif of thekidney sodium bicarbonate cotransporter (NBC1) disrupt its basolateral targeting and alpha-helical structure. J Membr Biol. 2009 Mar;228(2):111-24. Epub 2009 Mar 18. PubMed PMID: 19294449.

Soleimani M. The role of SLC26A6-mediated chloride/oxalate exchange in causingsusceptibility to nephrolithiasis. J Physiol. 2008 Mar 1;586(5):1205-6. PubMedPMID: 18310129; PubMed Central PMCID: PMC2375665.

Xu J, Song P, Miller ML, Borgese F, Barone S, Riederer B, Wang Z, Alper SL,Forte JG, Shull GE, Ehrenfeld J, Seidler U, Soleimani M. Deletion of the chloridetransporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairsacid secretion in the stomach. Proc Natl Acad Sci U S A. 2008 Nov18;105(46):17955-60. Epub 2008 Nov 12. PubMed PMID: 19004773; PubMed CentralPMCID: PMC2582584.

Barone S, Fussell SL, Singh AK, Lucas F, Xu J, Kim C, Wu X, Yu Y, Amlal H,Seidler U, Zuo J, Soleimani M. Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and generation of fructose-induced hypertension. J BiolChem. 2009 Feb 20;284(8):5056-66. Epub 2008 Dec 17. PubMed PMID: 19091748; PubMedCentral PMCID: PMC2643499.

Petrovic S, Barone S, Wang Z, McDonough AA, Amlal H, Soleimani M. Slc26a6(PAT1) deletion downregulates the apical Na+/H+ exchanger in the straight segmentof the proximal tubule. Am J Nephrol. 2008;28(2):330-8. Epub 2007 Nov 29. PubMed PMID: 18046080.

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