tumor cell biology program - Sylvester Comprehensive Cancer Center

Moraes, CT, Kenyon, L and Hao,
H. Mechanisms of human mitochondrial
DNA maintenance: the determining role
of primary sequence and length over
function. Molecular Biological Cell
10:3345, 1999.
Barrientos, A and Moraes, CT. Titrating
the effects of mitochondrial complex
I impairment in the cell physiology.
Journal of Biological Chemistry
274:16188, 1999.
Hao, H, Morrison, LE and Moraes,
CT. Suppression of a mitochondrial
tRNA gene mutation phenotype associated
with changes in the nuclear background.
Human Molecular Genetics
8:1117, 1999.
Barrientos, A, Muller, S, Dey, R,
Wienberg, J and Moraes, CT. Cytochrome
c oxidase assembly in primates
is sensitive to small evolutionary variations
in amino acid sequence. Molecular
Biology and Evolution 17:1508,
2000.
Dey, R, Barrientos, A and Moraes,
CT. Functional constraints of nuclearmitochondrial
DNA interactions in
xenomitochondrial rodent cell lines.
Journal of Biological Chemistry 275:
31520, 2000.
Dey, R, Tengan, CH, Morita, MPA,
Kiyomoto, BH and Moraes, CT. A novel
myopathy-associated mitochondrial
DNA mutation altering the conserved
size of the tRNA(Gln) anticodon loop.
Neuromuscular Disorders 10:488, 2000.
Rana, M, de Coo, I, Diaz, F, Smeets,
H and Moraes, CT. An out-of-frame
cytochrome b gene deletion from a patient
with parkinsonism is associated
with impaired complex III assembly and
an increase in free radical production.
Annals of Neurology 48:774, 2000.
Dey, R and Moraes, CT. Lack of
oxidative phosphorylation and low mitochondrial
membrane potential decrease
susceptibility to apoptosis and do
not modulate the protective effect of Bclx
L
in osteosarcoma cells. Journal of Biological
Chemistry 275:7087, 2000.
Hu, Y, Moraes, CT, Savaraj, N,
Priebe, W and Lampidis, TJ. Rho(0) tumor
cells: a model for studying whether
mitochondria are targets for rhodamine
123, doxorubicin and other drugs. Biochemical
Pharmacology 60:1897, 2000.
Moraes, CT. A helicase is born.
Nature Genetics 28:200, 2001.
Moraes, CT. What regulates mitochondrial
DNA copy number in animal
cells? Trends in Genetics 7:199, 2001.
Moraes, CT, Dey, R and Barrientos,
A. Transmitochondrial technology in
animal cells. Methods In Cell Biology
65:397, 2001.
Xu, G, Dave, KR, Moraes, CT,
Busto, R, Sick, TJ, Bradley, WG and
Perez-Pinzon, MA. Dysfunctional mitochondrial
respiration in the wobbler
mouse brain. Neuroscience Letters
300:141-144, 2001.
HIGHLIGHTS/DISCOVERIES
• Dr. Moraes’ group has found that cells
with defective mitochondrial respiration
can be more resistant to cell death.
This is a counterintuitive concept, as
it was thought that the less energy a
cell has, the easier it is to kill it. However,
programmed cell death does require
a considerable amount of ATP
(energy) to occur. These findings may
explain the presence of mtDNA mutations
in some cancers.
Kenneth E. Rudd, Ph.D.
Associate Professor of
Biochemistry and
Molecular Biology
DESCRIPTION OF RESEARCH
Dr. Rudd’s research focuses on functional
characterization of a selected
set of genes and gene products of Escherichia
coli. The 4.6 Mb genome of E. coli
is now completely sequenced and contains
over 4,100 protein-encoding genes.
Less than half of these genes have been
functionally characterized. Most protein
sequences can be organized into families
based upon homologous relationships.
Some families are restricted to the bacterial
domain of life whereas others contain
Ancient Conserved Regions (ACRs)
that are present in both bacterial and
eucaryotic proteins, including human
proteins. Their genome-scale homology
analysis is used both to organize the genes
of E. coli into functional predictionbased
classes and to identify a set of genes
to characterize experimentally.
Their characterization of E. coli
ORFs (Open Reading Frames) of unknown
biological function is directed at
selected proteins that fall into different
functional classes based on homologous
relationships. Some functional predictions
are quite specific. However, sometimes
the functional prediction is limited
to a general type of protein activity, for
example a membrane permease of unknown
specificity. In other cases, no
functions have been attributed to any
member of the homologous family, even
though the family might be quite widespread
in nature. Their approach includes
determining the phenotype associated
with mutations in the genes of interest
as well as cloning, overproducing, purifying,
and characterizing the proteins of
interest. They are particularly interested
in proteins of less than 150 amino acids
in length as they are among the most
difficult to analyze using bioinformatic
approaches alone. Some of the proteins
they are characterizing have predicted
functions that include protein phosphorylation,
ligand binding, protein-protein
interactions, transport functions and protease
activity. They hope that this selective
top-down approach to functional
genomics will illuminate important new
functions, not just in E. coli, but in organisms
with related proteins as well.
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UM/Sylvester Comprehensive Cancer Center Scientific Report 2002