RESEARCH
FOCUS: MOLECULAR BIOLOGY IN THE SERVICE OF PUBLIC
HEALTH
Prevention of HIV-1 mother-to-child transmission
(MTCT) has been successfully implemented in the
developed world, where the annual incidence of
MTCT has been reduced to less than 2%; for example,
in 2005, the USA reported 86 cases of perinatally
acquired HIV (Ref.).
However, in the developing world, HIV-1 MTCT remains
a serious public health problem, with approximately
530,000 children newly HIV-1 infected in 2006
(http://www.unaids.org/).
Approximately 20% of all MTCT occurs in utero,
and although many countries are scaling up programs
to provide single-dose nevirapine prophylaxis
(http://www.globalfundatm.org/
), this treatment will not reduce in utero
MTCT.
The
Kwiek lab seeks to better understand the molecular
biology and epidemiology of in utero HIV-1 MTCT.
This will be accomplished, in collaboration with
colleagues at both The Ohio State University and
The Malawi College of Medicine, by addressing
the following questions:
1.
Are specific HIV-1 envelope genotypes or phenotypes
associated with HIV-1 MTCT?
2.
Does the placenta represent a unique HIV-1 compartment?
3.
Where does HIV-1 localize in the placenta?
4. Do
transmitted HIV-1 envelope genes have enhanced
tropism against primary placental trophoblasts?
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Juliano,
J., Kwiek, J.J., Mwapasa, V.,
Meshnick, S.R. Development of a Multiple-Site
Specific Heteroduplex Tracking Assay that can
Detect Low Prevalence pfcrt K76T Mutations. Emerging
Infectious Diseases 2007, 13(6):872-7.
Kwiek, J.J., Alker, A.P., Kalilani,
L., Wenink, E.C., Chaponda, M., E., Meshnick,
S. R. Estimating True Antimalarial Efficacy by
Heteroduplex Tracking Assay in Patients with Complex
Plasmodium falciparum Infections. Antimicrobial
Agents and Chemotherapy 2007, 51(2):521-7.
Mwapasa,
V., Rogerson, S.J., Kwiek, J.J.,
Molyneux, M.E., Kamwendo, D.D.,
Tadesse, E., Chaluluka, E., Wilson, P.E., Meshnick,
S.R. Is Maternal Syphilis Infection a Risk Factor
for HIV Mother-to-Child Transmission? AIDS 2006,
20:1869-77.
Kwiek
J.J., Mwapasa V., Milner, D., Alker,
A., Miller, W., Ou, C.Y., Tadesse, E., Molyneux,
M.E., Rogerson, S.J., Meshnick, S.R. Maternal-fetal
Microtransfusions and HIV-1 Mother-to-Child Transmission
in Malawi. PLoS-Medicine 2006, 3(1):e10.
Ngrenngarmlert,
W., Kwiek, J.J., Kamwendo, D.D.,
Ritola, K., Swanstrom, R., Wongsrichanalai, C.,
Ittarat, W., Miller, R.S., and Meshnick, S.R.
Measuring Allelic Heterogeneity in Plasmodium
falciparum by Heteroduplex Tracking Assay.
American Journal of Tropical Medicine and Hygiene
2005, 72: 694-701.
Kwiek
J.J., Haystead, T.A., Rudolf, J. The
Kinetic Mechanism of Quinone-Oxidoreductase 2
and its Inhibition by the Anti-Malarial Quinolines.
Biochemistry 2004, 43 (15): 4538-4547.
Graves P.R.,
Kwiek J.J., Fadden P., Ray, R.,
Hardeman, K., Coley, A. M., Foley, M., Haystead,
T. A. Discovery of Novel Targets of Quinoline
Drugs in the Human Purine Binding Proteome. Mol
Pharmacol 2002, 62:1364-1372. |
