understanding the immunobiology of host-parasite interactions.

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Alan Scott

Professor

 

 

Academic Degrees

PhD Auburn University 1981

 

Departmental Affiliation

Molecular Microbiology and Immunology

 

 

Joint Departmental Affiliations

Biochemistry and Molecular Biology, International Health,

Environmental Health Sciences

Center and Institute Affiliations

Malaria Research Institute, EHS Center in Environmental Urban Health,

Center for Human Nutrition

 

Departmental Address

 

 

ascott

Phone:

Fax:

 

Research

My laboratory is interested in understanding the immunobiology of

host-parasite interactions. The specific focus of this interest is on

the ability of certain helminth parasites to actively modify host

immunity and control the Th1-Th2 axis of the immune response. In these

studies the lab has taken on two lines of investigation that have a

common theme of defining the molecular basis for control of Th2

responses. The first line of investigation concentrates on the use of

a murine model of human asthma and allergy to define the genetic and

molecular determinants that result in the disregulation of immune

response to traditional allergens. In the second line of research we

study filarial nematode infections with the goal of identifying the

molecules released by the parasite that modify the immune

responsiveness of the host and result in a highly polarized Th2

immunity and chronic infection. It is anticipated that an

understanding of the mechanism of action of the parasite-derived

molecules on the immune response will inform us of the molecular and

cellular bases for the generation and regulation of asthma and allergy

in humans. Likewise, understanding the regulation of Th2 immunity in

asthma and allergy will provide us with a catalog of molecules and

pathways that could be targeted for disruption by parasite-derived

molecules. In addition to providing fundamental insight into

regulation of Th2 immunity that can lead to control of disease, the

work has implications for autoimmunity and transplantation biology.

 

Asthma/Allergy - Under the auspices of funding from NHBLI/NIH, I am

the PI of a grant that employs genomic and proteomic approaches to

define the molecules and pathways that are key in the regulation of

pulmonary inflammation, repair and remodeling. Gene chip-based

expression analysis is being used to define the genes that are

regulated at the transcriptional level during inflammation in the

lung. Studies are being carried out in murine models of major human

diseases with particular emphasis on allergy/asthma. Genes identified

as potentially important in inflammation/repair/remodeling are

validated in the murine system. Once validated, the orthologous gene

in humans is identified and studied for its relevance to human

disease. In the context of the same project, we are also using

proteomic approaches to identify genes/proteins important in the

inflammation/repair/remodeling process that are not regulated at the

transcriptional level. These studies utilize 2-dimensional gel

analysis and liquid chromatography-mass spectroscopy to define changes

in the proteome. As with the gene expression analyses, both mouse

models and clinical samples are being utilized to define the proteins

that are key to pulmonary inflammation/repair/remodeling. In

association with this project, I am the director of a

microarray/proteomics core facility.

 

Filarial Nematodes - The second major project in the lab focuses on

the immunobiology of filarial nematode infections. Filarial nematodes

establish long-term chronic infections that last for decades while

causing little or no overt pathology in a majority of infected

individuals. This maintenance of an asymptomatic status is made more

remarkable by the fact that the adult filarial parasites take up

residence within the lumen of efferent lymphatic vessels directly down

stream from major lymph node clusters. We hypothesize that this

tropism for the efferent lymphatics places the parasite in an ideal

position to affect control of the immune response through the release

of factors that actively modulate and selectively suppress the immune

response of the host. One of the phenotypes of the parasite-mediated

immune modulation is the generation of a highly polarized Th2

response. Th2 immunity strongly correlates with chronicity in this and

many other infections. The goal of the work is to define the

composition of the 300+ polypeptides released by the model filarial

worm Brugia malayi and to identify the molecules that mediate immune

modulation. The project is being carried out utilizing both proteomic

and genomic approaches to define the protein factors released by the

parasites. Whenever possible, orthologous genes in C. elegans are

identified and studied. In a related project, I a member of the team

centered at TIGR that is carrying out whole genome shotgun sequencing

B. malayi.

 

 

 

Keywords

Molecular Microbiology and Immunology, parasitic nematodes, biology,

infections, parasites, filarial nematodes, asthma, allergy, gene

expression analysis, genomics, gene array, micro array

 

Selected Publications

Tarr DE and Scott AL. 2004. A family of MSP-domain proteins

transcribed by nematode sperm cells. Mol Biochem Parasitol. 137:87-98

 

Klein SL, Cernetich A, Hilmer S, Hoffman EP, Scott AL and Glass GE.

2004. Sex and Hantavirus infection: differential expression of

immunoregulatory genes in male and female Norway rats. J Med.

Virology. 8:742-749

 

Reece JJ, Siracusa MC and Scott AL. 2006. Innate immune responses to

lung-stage helminth infection induce alternatively activated alveolar

macrophages. Infect. Immun. 74:1-12.

 

Cernetich A, Garver LS, Jedlicka AE, Klein PW, Kumar N, Scott AL and

Klein SL. 2006. Involvement of gonadal steroids and gamma interferon

in sex differences in response to blood-stage malaria infection.

Infect. Immun. 74:3190-3203.

 

Page KR, Scott AL and Manabe YC. 2006. The expanding realm of

heterologous immunity: friend or foe. Cell Microbiol. 8:185-196.

 

Page KR, Jedlicka AE, Fakheri B, Noland GS, Kesavan AK, Scott AL,

Kumar N and Manabe YC. 2005. Mycobacterial-induced potentiation of

type 1 immune responses and protection against malaria is

host-specific. Infect. Immun. 73:8369-8380.

 

Tarr DE and Scott AL. 2005. MSP domain protein 1 from Ascaris suum and

its possible role in the regulation of major sperm protein-based

crawling motility. Mol Biochem Parasitol. 143:165-172.

 

Irizarry RA, Warren D, Spencer F, Biswal S, Frank BC, Gabrielson E,

Garcia JGN, Geoghegan J, Germino G, Griffin C, Hilmer SC, Eric Hoffman

E, Jedlicka AE, Kawasaki E, Kim IF, Morsberger L, Lee H, Petersen D,

Quackenbush J, Scott AL, Wilson M, Yang Y, Ye SQ, Yu W. 2005. Multiple

Lab Comparison of Microarray Platforms. Nature Methods. 2:345-350.

 

Aguilar R, Jedlicka AE, Mintz M, Machairaki V, Scott AL and Dimopoulos

G. 2005. Global gene expression analysis of Anopheles gambiae

responses to microbial challenge. Insect Biochem Mol Bio. 35:709-719.

 

Gbakima AA, Appawu MA, Dadzie S, Karikari C, Sackey SO, Baffoe-Wilmot

A, Gyapong J and Scott AL. 2005. Lymphatic filariasis in Ghana:

establishing the potential for an urban cycle of transmission. Trop

Med Internatl Hlth. 10:387-392.

 

Tarr DE and Scott AL. 2005. MSP-domain proteins. Trends Parasitol.

21:224-231.

 

Brown RH, Hamilton RG, Mintz M, Jedlicka AE, Scott AL and Kleeberger

SR. 2005. Genetic predisposition to latex allergy: the roles of IL-13,

IL-4 and IL-18. J. Anesthesiology. 102:496-502.

 

Tarr DE and Scott AL. 2004. MSP domain proteins show enhanced

expression in male germ line cells. Mol Biochem Parasitol. 137:87-98.

 

Klein SL, Cernetich A, Hilmer S, Hoffman EP, Scott AL and Glass GE.

2004. Sex and Hantavirus infection: differential expression of

immunoregulatory genes in male and female Norway rats. J Med.

Virology. 8:742-749.

 

Kunchithapautham K, Padmavathi B, Narayanan RB, and Kaliraj, P. Scott

AL 2003. Thioredoxin from Brugia malayi: defining a 16 kDa class of

thioredoxins from nematodes. Infect Immun. 71:4119-4126.

 

Zang X, Taylor P, Wang JM, Meyer DJ, Scott AL, Walkinshaw MD, Maizels

RM. 2002. Homologues of human macrophage migration inhibitory factor

from a parasitic nematode: Gene cloning, protein activity and crystal

structure. J. Biol. Chem. 277: 44261-44267.

 

Gnanasekar M, Rao KVN, Chen L, Narayanan RB, Geetha M, Scott AL,

Ramaswamy, K, and Kaliraj, P. 2002. Molecular characterization of a

calcium binding translationally controlled tumor protein homologue

from the filarial parasites Brugia malayi and Wuchereria bancrofti.

Mol Biochem Parasitol. 30;121:107-118.

 

Klein SL, Marson AL, Scott AL, Ketner G and Glass GG. 2002. Neonatal

sex steroids affect responses to Seoul virus infection in male but not

female Norway rats. Brain, Behaviour and Immunity. 16:736-746.

 

Marson A, Tarr DE and Scott AL. 2001 Macrophage migration Inhibitory

factor (mif) expression is significantly elevated in C. elegans dauer

larvae. Gene. 278: 53-62.

 

Maizels R, Blaxter M and Scott AL 2001. Immunogenomics. Parasitology.

23: 327-344.

 

Triteeraprapab S, Kanjanopas K, Suwannadabba S, Sangprakarn S,

Poovorawan Y and Scott AL. 2000. Transmission of the nocturnal

periodic strain of Wuchereria bancrofti by Culex quinquefasciatus:

establishing the potential for urban filariasis in Thailand.

Epidemiol. Infect 125:207-212.

 

Williams SA, Lizotte-Waniewski MR, Foster J, Guiliano D, Daub J, Scott

AL, Slatko B, and Blaxter ML. 2000 The filarial genome project:

Analysis of the nuclear, mitochondrial and endosymbiont genomes of

Brugia malayi. Int J Parasitol. 30: 411-420.

 

 

 

 

 

 

 

 

 

 

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