Faculty & Research
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Svetlana N. Radyuk, Ph.D.Research Associate ProfessorGraduated from Lomonosov Moscow State University with MS in Chemistry Ph.D.: (Molecular Biology and Biochemstry) Research Institute for Applied Microbiology, Russia Postdoctoral training: |
Office: 340-DLS Tel: 214.768.2892 Fax: 214.768.3955 Email: snradyuk@smu.edu Lab: 317-DLS Tel: 214.768.2065 |
Research Interests
Immunity and aging
My main
interest is to understand the interrelationship between immunity and
aging.
Aging is
characterized by malfunctioning of immunity.
Deregulation of the immune response during aging can result in
cancer and other age-related diseases.
The study in our group is aimed at elucidating the mechanisms
that underlie such deregulation in order to
develop proper interventions.
The most dramatic changes associated with aging involve immunity:
Decreased ability to mount an immune response
Increased susceptibility to infectious diseases and cancer
Reduced responsiveness to vaccination
Impaired function and clonal expansion of T and B cells
Aged mice have significantly lower levels of all TLRs
Enhanced innate immunity in older organisms give rise to an excessive
immune response and inflammation
Extended longevity correlates with optimal functioning of innate
immunity, attenuation of pro-inflammatory responses and decrease in
pathogen burden
Enhanced pathogen resistance is a feature of strains with a long-lived
background
The response
and resistance of macro-organisms to microbial challenges comes at a
cost:
While bolstered immunity offers protection
against invaders, it may also elicit
damage to host cells and tissues, which ultimately could lead to
functional deficits
Excessive production of immunity effectors can also place substantial
energy demands on the cellular machinery, which may result in
trade-offs that negatively impact
the maintenance of
cellular homeostasis
Immune pathways are similar to those in humans
Life span is 60-70 days
Genetically tractable
Variety of genetically modified strains available at stock centers
Reverse correlation between typical
Drosophila
life span and changes in the levels of immune effectors (antimicrobial
peptides, AMPs) and accumulation of oxidative stress and shifts in redox
to more pro-oxidized state
The focus of my current
research is to understand the role of redox regulation of the innate
immunity and aging. One of
the major regulators of cellular redox are enzymes named thiol-dependent
peroxidases, or peroxiredoxins.
They are widespread in all three kingdoms, highly conservative in
all organisms starting from bacteria and extending into humans, Involved
in a number of redox-related cellular functions: differentiation,
proliferation, apoptosis, signaling processes, immune response.
Reactive oxygen
and nitrogen species (ROS and RNS),
produced
during metabolic reactions, inflammation, and phagocytosis, not only
cause tissue damage, but also act as messengers in signaling pathways,
including modulation of the immune responses.
The aim is to determine by how
to
maintain the “correct” levels of ROS/RNS in order to minimize the tissue
damage and at the same time not to compromise the immune response.
I
am testing a hypothesis that peroxiredoxins may control the ‘switch’ in
the redox state, excessive immune response and thus accelerated death.
To address these questions, we are using a wide range of
molecular biology and genetics techniques.
Practical terms: examine the differences in redox signaling that
modulate immunity and aging in both young and old organisms; develop
interventions, which take into account the differential effects on young
versus old individuals.
Selected Publications
Radyuk SN, Rebrin I, Klichko VI, Sohal BH, Michalak
K, Benes J, Sohal RS, Orr WC.
Mitochondrial peroxiredoxins are critical for the maintenance of
redox state and the survival of adult Drosophila.
Free Radic Biol Med. 2010 Dec 15;49(12):1892-902.
Radyuk SN, Michalak K, Klichko VI, Benes J, Orr WC. Peroxiredoxin 5
modulates immune response in Drosophila.
Biochim Biophys Acta. 2010 Nov;1800(11):1153-63.
Radyuk SN, Michalak K, Klichko VI, Benes J, Rebrin I, Sohal RS, Orr WC.
Peroxiredoxin 5 confers protection against oxidative stress and
apoptosis and also promotes longevity in Drosophila.
Biochem J. 2009 Apr 15;419(2):437-45.
Radyuk SN, Rebrin I, Luchak JM, Michalak K, Klichko VI, Sohal RS, Orr
WC. The catalytic subunit of
Drosophila glutamate-cysteine ligase is a nucleocytoplasmic shuttling
protein.
J Biol Chem. 2009 Jan 23;284(4):2266-74. Epub 2008 Nov 26.
Legan SK, Rebrin I, Mockett RJ, Radyuk SN, Klichko VI, Sohal RS, Orr WC.
Overexpression of glucose-6-phosphate dehydrogenase extends the
life span of Drosophila melanogaster.
J Biol Chem. 2008 Nov 21;283(47):32492-9. Epub 2008 Sep 22.
Michalak K, Orr WC, Radyuk SN.
Drosophila peroxiredoxin 5 is the second gene in a dicistronic
operon.
Biochem Biophys Res Commun. 2008 Apr 4;368(2):273-8.
Luchak JM, Prabhudesai L, Sohal RS, Radyuk SN, Orr WC.
Modulating longevity in Drosophila by over- and underexpression of
glutamate-cysteine ligase.
Ann N Y Acad Sci. 2007 Nov;1119:260-73.
Radyuk SN, Michalak K, Rebrin I, Sohal RS, Orr WC.Effects of ectopic
expression of Drosophila DNA glycosylases dOgg1 and RpS3 in
mitochondria.
Free Radic Biol Med. 2006 Sep 1;41(5):757-64.
Orr WC, Radyuk SN, Prabhudesai L, Toroser D, Benes JJ, Luchak JM,
Mockett RJ, Rebrin I, Hubbard JG, Sohal RS.
Overexpression of glutamate-cysteine ligase extends life span in
Drosophila melanogaster.
J Biol Chem. 2005 Nov 11;280(45):37331-8.
Radyuk, S.N., Klichko, V.I. and Orr, W.C. (2004)
Profiling Cu,Zn-superoxide dismutase in Drosophila melanogaster - a
critical regulatory role for intron/exon sequence within the coding
domain. Gene. 328,
37-48.
Klichko, V.I., Radyuk, S.N. and Orr, W.C. (2004) Profiling catalase gene
expression in Drosophila melanogaster during development and aging.
Archives of Insect Biochemistry and Physiology.
56, 34-50.
Radyuk S.N., Sohal R.S., Orr W.C. (2003).
Thioredoxin peroxidases can foster cytoprotection or cell death
in response to different stressors - a study of thioredoxin peroxidase
under- and over-expression in Drosophila cells. Biochem J. 2003 May 1;371(Pt
3):743-52.
Mockett R.J., Radyuk S.N., Benes J.J., Orr W.C., Sohal R.S. (2003).
Phenotypic effects of familial amyotrophic lateral sclerosis
mutant Sod alleles in transgenic Drosophila. Proc Natl Acad Sci U
S A 2003 Jan 7;100(1):301-6
Radyuk, S.N., Klichko, V.I., Spinola, B., Sohal, R.S., Orr, W.C. (2001).
The peroxiredoxin gene family in Drosophila melanogaster. Free Radic.
Biol. Med., Nov 1;31(9):1090-100
Support
Current:
R21 07/01/2011-06/31/2013 (Principal Investigator in a subcontract with Oregon State University) Funded by National Institutes of Health, Direct cost $102970 for two years, ‘Role of circadian clocks in maintaining a healthy nervous system’.
R01
04/01/2011-03/31/2016 (Principal Investigator) Funded by National
Institutes of Health, Direct cost $205000 per year, ‘Peroxiredoxins,
immune signaling and aging’
Prior:
R21 01/01/05-12/31/06 (Principal Investigator) Funded by National
Institutes of Health, Direct cost $125000 per year, ‘The Role of
Peroxiredoxins in Immunity and Aging’
SBIR 08/16/04-12/16/05 (Sub-Contract) Funded by US Airforce; Direct cost
$75000 for 16 months, ‘Automated Individual Real-Time Toxic Exposure
Monitoring (AIRTEM) System
Education
| 1979: | MS Chemistry, M.V.Lomonosov Moscow State University, Russia. |
| 1990: | PhD Biology Research Institute for Applied Microbiology, Russia. |
Professional Experience
| 2003-present | Research Assistant Professor, Southern Methodist University, Dallas, TX. |
| 2002-2003: | Senior Scientist, Advanced Biosystems, Inc., Manassas, VA. Affiliate Professor, George Mason University, Manassas, VA. |
| 1996-2002: | Postdoctoral Research Associate, Southern Methodist University, Dallas, TX. |
| 1991-1996: | Principal Research Scientist, Research Institute for Viral Preparations, Moscow, Russia. |
| 1982-1991: | Junior Research Scientist, Research Institute of Applied Microbiology, Obolensk, Russia. |
| 1979-1982: | Engineer, Research Institute of Applied Chemistry, Zagorsk, Russia. |
