EXAMPLES OF VCU UNDERGRADUATE RESEARCHERS - PAST AND PRESENT Students are Listed with their Advisor and a description of their research.
Melinda Christie
Slattum "Age- and Gender-Related Differences in the Sensitivity to Ethanol"
The
elderly appear to be more sensitive to the effects of alcohol and other
drugs. Two processes may contribute to this apparent increased sensitivity:
altered pharmacokinetics (PK) or altered pharmacodynamics (PD) It
is hypothesized that the increased sensitivity is due primarily to the
CNS pharmacodynamics (PD) rather than the pharmacokinetics (PK) of
ethanol. This study will characterize the PK and PD of intravenous
ethanol in elderly males and females, determine whether the elderly are
more sensitive to ethanol intoxication than young subjects, and assess
the effect of gender on age-related differences in sensitivity to ethanol
effects.
Elizabeth Darrenkamp
Garrett "Isolation of cDNA fragments of HCV" The
most common form of chronic viral hepatitis in the U.S. is called the Hepatitis
C Virus and is transmitted via body secretions. Unfortunately, there
are no chemotherapeutic treatments for the disease presently. My research
project objective is to isolate cDNA fragments of the Hepatitis C Viral
Genome and obtain a single band of appropriate molecular weight.
The fragments of HCV will be confirmed and used to construct ribozymes
as potential therapeutic agents which will target the HCV genome.
Imran Jafri
Ramoa "Studies of Developmental Vision in Ferrets"
Ferrets, like primates, possess binocular vision, however, they are born
with relatively underdeveloped vision. Visual development can be
studied after birth. This project will evaluate the connections between
the retina and the lateral geniculate nucleus in newborn ferrets between
14 and 28 days of age. Critical proteins, including the NMDA receptor,
will also be evaluated during this process.
Jeffrey Kirk
Wu-Pong "Role of Sequence on Oligonucleotide Structure, Transport
and Activity" Oligonucleotides (ODN) are used therapeutically to
bind to complementary mRNA, thus inhibiting expression of certain genes.
This research project is intended to study the role of sequence on the
stabilization of secondary structure, transport and activity of ODNs.
Specifically, the stability and transport of G-rich sequences which contain
various flanking sequences will be evaluated during this project.
Jay Khosla Tombes
"Role of delta CaMK-II Isozyme Expression in Human Leukemic Cell Differentiation"
The
differentiation of malignant hematopoietic cells into monocytes, granulocytes
or neutrophils can be induced. CaMK-II, the multifunctional calcium/calmodulin-dependent
protein kinase, is down-regulated in human leukemic cells and CaMK-II overexpression
causes decreased cell growth in embryonic fibroblasts. This project
will evaluate whether specific isozymes of CaMK-II can induce the differentiation
of leukemic cells in vitro and thus serve as a possible model for
differentiation-based therapies.
Susan Milhausen
Kauma "Role of Cytokines during Implantation and Pregnancy"
LIF
and IL-11 are cytokines necessary for implantation to occur, as they influence
trophoblast and placental growth. IL-11 can induce growth of some
trophoblast cell lines in vitro, but not others. This project will
evaluate whether variant cell growth responses are due to a difference
in IL-11 receptors.
Lanre Omojokun
Shapiro "A Study of Brain Damage and Auditory Dysfunction
in Bilirubin Toxicity Using Animal and Cell Culture Models" Bilirubin,
a yellow inexcretable pigment, is a breakdown product of hemoglobin in
the blood. Most newborns experience a high concentration of bilirubin,
due to the liver's inability to produce sufficient amounts of glucuronyl
transferase, the enzyme that converts bilirubin into an excretable water-soluble
form. After few days, however, the liver matures and is capable of
converting bilirubin, and bilirubin decreases to a normal level.
Some newborns, particularly premature newborns, never produce enough glucuronyl
transferase to convert bilirubin, thus resulting in hyperbilirubinemia.
Such neonatal bilirubin toxicity damages areas of the brainstem, thereby
causing hearing loss and other complications of brain damage. My
research will focus on the susceptibility of rat pups to bilirubin-induced
damage of the neonatal auditory system of the rat, with applications to
human newborns.
David Paik Tombes
"Characterization of CaMK-II Targeting Domains" Domains
necessary for intracellular CaMK-II targeting to the cytoskeleton are being
characterized by deletion mutagenesis and transfection back into a variety
of cells. Live-cell fluorescent digital imaging will be used to evaluate
dynamic targeting.
Shannon Pratt
Christie "Mutagenesis of the DNA binding site of the
P2 Phage Ogr Protein" The P2 Pgr protein is a transcription factor
essential for late gene expression by the P2 bacteriophage. This
project will use mutant promoters to select for mutant transcription factors
which have alterations in their DNA binding. These transcription
factors will then be characterized to help define important amino acid
determinants in DNA binding.
Roanna Trisdorfer
Barbour "Studies on Phospholipid Dynamics in Mammalian
Cells" In mammalian cells, the two major
choline-containing phospholipids are phosphatidylcholine (PC) and sphingomyelin
(SM). The ratio of these two lipids is strictly maintained in most
mammalian cells. When Chinese Hamster Ovary Cells (CHO cells) are
transfected with the gene encoding the enzyme CTP:phosphocholine cytidylyltransferase
(CT) they have been shown to contain about 20% more PC than untransfected
cells. Hence, we predict that the transfected cells will exhibit
increased SM mass to balance the already observed increased PC mass. I
will perform experiments comparing the amount of SM mass in the transfected
and untransfected CHO cells. If SM mass is increased in the transfected
cells, I will do further experiments to determine whether this increase
in mass is the result of (1) an increase in the amount of SM synthesized,
(2) a decrease in the amount of SM catabolized, or (3) the transfer of
the choline head group from PC to SM.
Alex Young Baumgarten
"Effect
of Integrins on Cardiac Cell Volume Regulation" Cell
volume regulation is controlled by stretch-activated ion channels (SACs).
There is a relationship between SAC activity and integrin receptors. Integrins
bind to extracellular material and transmit mechanical force into the cell
causing cytoskeletal rearrangements and kinase cascades. The hypothesis
of this research is that one of the functions of the integrin induced-kinase
cascades is to modulating SAC activity, affecting cell volume regulation.
To explore this possibility, magnetic beads coated with integrin ligands
are used to create a mechanical force that is transmitted into myocytes
via integrin receptors.
Ben Harvey Bullock
"Spinal cord Injury Studies"
Roxanne George Barbour
"Phospholipid Metabolism in Tumor Cell Lines"
Jonathan Kurz Churn
"Calcineurin Activity in Status Epillepticus"
Shakun Gupta Grant
"Histone DeAcetylase and Combinatorial Leukemia Therapy"
Dr. Grant's work is on combining conventional chemotherapies that alone
may not have a very significant effect but when put in different combinations,
have a great effect. I started on a project combining a conventional
drug with a histone deacetylace in a particular cell line. This combination
showed promise and I worked on a part of this ongoing project to find another
drug with a different histone deacetylace in a different leukemia cell
line to show the generalizability of such a treatment.
Debraj Mukherjee Churn
"Pathological Caspase Activation In Status Epilepticus"
Status epilepticus (SE) is a severe medical condition defined as continuous
seizure activity lasting for thirty minutes or more (Bleck 1991). It is
estimated that the condition affects over one hundred thousand people in
the United States each year (DeLorenzo et al. 1995, 1996). While the development
of SE may induce death rapidly, the physiological changes that accompany
SE may also have lasting affects on the functioning of neurochemical pathways
in the brain (Wasterlain et al. 1993; Rice et al. 1996; Fountain 2000).
Research has implicated changes in calcium-regulated mechanisms as leading
to pathological conditions like SE (Pal et al. 1999; Parsons et al. 2000).
Research has further implied that calcium influx via the NMDA receptor
is responsible for increased activity of calcineurin, a neuronally enriched,
calcium-dependent phosphatase (Montoro et al. 1993; Pallen and Wang 1985).
As a role player in the induction of apoptosis and the depression of GABA
receptor activity, increased activity of calcineurin in neuronal cells
following SE makes the study of this enzyme and of the mechanisms that
activate it relevant to the study of the post SE neurochemical changes
in the brain (Springer et al. 2000; Huang and Dillon 1998). One possible
set of intermediates between the influx of calcium via the NMDA receptor
and the increased activity of calcineurin following SE are the cysteine
aspartic acid-specific proteases, collectively known as caspases. The central
role that caspases play in apoptosis mechanisms have recently been understood,
although the role that caspases may play in neuronal degeneration following
SE, particularly as an intermediate in the mechanism involving NMDA receptors
and calcineurin, has not been thoroughly explored (Nicholson and Thornberry
1997). Caspases promote apoptosis by disabling cellular mechanisms and
by cleaving structural components (Nicholson and Thornberry 1997). Of the
caspases involved in apoptosis, caspase-3, caspase-6, and caspase-7 have
been identified as executioners (Slee et al. 2001). These executioners
are the final caspases in a cascade of events within the cell that eventually
cleave products within the cell leading to apoptosis. This project will
attempt to determine the role that executioner caspases may play in cellular
mechanisms leading to increased calcineurin activity following status epilepticus
in the rat brain.
Mario Saavedra Fillmore
"MT1-MMP Promoter in Gliomas" I am cloning the MT1-MMP
promoter into a luciferase vector. The promoter region will be mutated
and then transfected into cells for experimentation. The purpose
is to study the different structural parts of the promoter and the effects
of different signaling pathways on the promoter, by locating the regions
in the promoter that cause high MT1-MMP expression in gliomas. We
hope to mutate those regions to decrease or eliminate tumor cell invasiveness
and proliferation.
Robin Bhavsar Churn
"Calcineurin Activity in Status Epillepticus"
Patrick Sachs Holt
"Human Telomerase Activity in Vitro"
Bina Patel Bear
"Adoptive Immunotherapy Experiments" I am working with Dr.
Holt and Dr. Bear. I am vaccinating mice against a tumor cell line
called 4T1-hTERT. The vaccine should be able to protect against tumor cells
because it is specially engineered to work against hTERT which is found
in most cancers.Ý To do the experiment, I vaccinate one group of mice (6
mice) with the vaccine and another group of mice with alum and the vaccine
once a week for three weeks.Ý I challenge the fourth week and then measure
the tumors.Ý ÝI am confirming whether the 4T1-hTERT cell line makes hTERT
as a contro experiment. There are many other projects that may be offshoots
of this central experiment.
Bic Cung Lloyd
"Cloning _-Globin Constructs to be Used in the Study of _-Globin Gene Regulation"
In humans, the genes of the _-globin locus switch from expressing
_-globin in the fetal stage to _-globin in the adult stage. The molecular
mechanism of this gene-switch has been studied for past few decades; we
hope that a better understanding of the underlying factors regulating the
sequential expression of these genes will eventually lead to more effective
treatments of hemoglobinopathies such as Sickle Cell Anemia.