Alejandro Aballay, Ph.D., Pharm.D., M.A.

Associate Professor in the Department of Molecular Genetics and Microbiology

Department:
Molecular Genetics and Microbiology

Email:
aaballaydukeedu

Mailing Address:
Box 3054, DUMC
Durham, NC 27710

Telephone:
919-684-2146

Training:
Ph.D., Universidad Nacional de Cuyo (Argentina)Pharm.D., Universidad Juan Agustin Maza (Argentina)M.A., Universidad Nacional de Cuyo (Argentina)

Last Updated:
April 16, 2009

Research Interests:
Our laboratory uses genetic and functional genomic methodologies to study the genetic basis of innate immunity. We infect the Caenorhabditis elegans model host with different human bacterial and fungal pathogens to understand host-pathogen interactions. We also use mammalian systems to study innate immunity and microbial pathogenesis.

Recent studies from our laboratory highlight the importance of the nervous system in the regulation of innate immune responses. Using a genetic approach we were able to demonstrate that specific neurons can regulate innate immunity. We are studying a number of signaling molecules that can be used by the nervous and immune system to communicate to each other.

Another line of investigation we are pursuing concerns the identification and characterization of receptors potentially involved in pathogen recognition and activation of immune responses. We have demonstrated that the only Toll-like receptor in C. elegans, TOL-1 is required to prevent the invasion of pharyngeal cells by the human pathogen Salmonella enterica. The study of candidate downstream components of the TOL-1 pathway indicate that TRF-1, but not IKB-1, may be required for the effects of TOL-1 in immunity and that there may be other downstream components that regulate TOL-1-mediated immunity in a redundant manner. We are also studying the immune function of the scavenger receptor CED-1 and a system of proteins involved in the unfolding protein response (UPR) that are required to prevent bacterial invasion of host cells.

In addition to pathogen recognition and activation of microbial killing pathways, another important aspect of innate immune response is fever. Fever is an ancient immune mechanism used by metazoans in response to microbial infections. In mammals, several studies have been conducted to understand the mechanism of fever elicitation and to develop antipyretic therapeutics. However, the mechanism by which increased temperature exerts its beneficial role remains unclear. We use C. elegans to study the mechanism by which increased temperatures activate the innate immune system.

We are also characterizing different C. elegans mutants that are either more resistant or more susceptible to
pathogens. Since several components of innate immunity are conserved among different organisms throughout evolution, understanding the basis of the immune response in C. elegans should provide new insight into some aspects of immunity in mammals.

Finally, we study the mechanisms by which bacterial virulence factors required for virulence in both nematodes and mammals target conserved innate immune pathways. We have demonstrated that S. enterica genes related to the type three secretion system (TTSS) are expressed in the C. elegans intestine and required for full virulence. We also showed that the S. enterica TTSS-exported effector protein SptP inhibits a conserved P38 MAPK signaling pathway. In addition to S.enterica, we also perform studies using a variety of human pathogens including Yersinia pestis, Pseudomonas aeruginosa, Staphylococcus aureus, and Cryptococcus neoformans.

Publications:
2009 -- Pubmed # 19270528 -- Aballay A. Neural regulation of immunity: role of NPR-1 in pathogen avoidance and regulation of innate immunity. Cell Cycle. 2009 Apr 1;8(7):966-9.

2008 -- Pubmed # 18801967 -- Styer KL, Singh V, Macosko E, Steele SE, Bargmann CI, Aballay A. Innate immunity in Caenorhabditis elegans is regulated by neurons expressing NPR-1/GPCR. Science. 2008 Oct 17;322(5900):460-4.

2008 -- Pubmed # 18606143 -- Haskins KA, Russell JF, Gaddis N, Dressman HK, Aballay A. Unfolded protein response genes regulated by CED-1 are required for Caenorhabditis elegans innate immunity. Dev Cell. 2008 Jul;15(1):87-97.

2008 -- Pubmed # 18682730 -- Fuhrman LE, Shianna KV, Aballay A. High-throughput isolation and mapping of C. elegans mutants susceptible to pathogen infection. PLoS ONE. 2008;3(8):e2882.

2008 -- Pubmed # 17975555 -- Tenor JL, Aballay A. A conserved Toll-like receptor is required for Caenorhabditis elegans innate immunity. EMBO Rep. 2008 Jan;9(1):103-9.

2007 -- Pubmed # 17644454 -- Styer KL, Click EM, Hopkins GW, Frothingham R, Aballay A. Study of the role of CCR5 in a mouse model of intranasal challenge with Yersinia pestis. Microbes Infect. 2007 Jul;9(9):1135-8.

2006 -- Pubmed # 17183709 -- Kerry S, TeKippe M, Gaddis NC, Aballay A. GATA transcription factor required for immunity to bacterial and fungal pathogens. PLoS ONE. 2006;1:e77.

2006 -- Pubmed # 16916933 -- Singh V, Aballay A. Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity. Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13092-7.

2005 -- Pubmed # 16170309 -- Styer KL, Hopkins GW, Bartra SS, Plano GV, Frothingham R, Aballay A. Yersinia pestis kills Caenorhabditis elegans by a biofilm-independent process that involves novel virulence factors. EMBO Rep. 2005 Oct;6(10):992-7.

2004 -- Pubmed # 15182677 -- Tenor JL, McCormick BA, Ausubel FM, Aballay A. Caenorhabditis elegans-Based Screen Identifies Salmonella Virulence Factors Required for Conserved Host-Pathogen Interactions. Curr Biol. 2004 Jun 8;14(11):1018-24.

2003 -- Pubmed # 12526744 -- Aballay A, Drenkard E, Hilbun LR, Ausubel FM. Caenorhabditis elegans innate immune response triggered by Salmonella enterica requires intact LPS and is mediated by a MAPK signaling pathway. Curr Biol. 2003 Jan 8;13(1):47-52.

2001 -- Pubmed # 11226309 -- Aballay A, Ausubel FM. Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis elegans from Salmonella typhimurium-mediated killing. Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2735-9.

2000 -- Pubmed # 11114525 -- Aballay A, Yorgey P, Ausubel FM. Salmonella typhimurium proliferates and establishes a persistent infection in the intestine of Caenorhabditis elegans. Curr Biol. 2000 Nov 30;10(23):1539-42.

2000 -- Pubmed # 10818110 -- Hoffenberg S, Liu X, Nikolova L, Hall HS, Dai W, Baughn RE, Dickey BF, Barbieri MA, Aballay A, Stahl PD, Knoll BJ. A novel membrane-anchored Rab5 interacting protein required for homotypic endosome fusion. J Biol Chem. 2000 Aug 11;275(32):24661-9.

2000 -- Pubmed # 10858243 -- Arenas GN, Staskevich AS, Aballay A, Mayorga LS. Intracellular trafficking of Brucella abortus in J774 macrophages. Infect Immun. 2000 Jul;68(7):4255-63.

1999 -- Pubmed # 10393811 -- Aballay A, Stahl PD, Mayorga LS. Phorbol ester promotes endocytosis by activating a factor involved in endosome fusion. J Cell Sci. 1999 Aug;112 ( Pt 15):2549-57.