Academic
Degrees
 Ph.D.
Microbiology, North Carolina
State University (1993)
B.S.
Biology, North
Carolina State University (1988)
Professional
Experience
2007-Present
Associate Professor, University of North Carolina at
Charlotte, Charlotte, NC
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2001-2007 Assistant Professor, University of North Carolina at
Charlotte, Charlotte, NC
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2000-2001
Research Assistant Professor, University of North
Carolina at Charlotte, Charlotte, NC
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1997-2000
Research Analyst, University of North Carolina at
Chapel Hill, Chapel Hill, NC
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1993-1997
Postdoctoral Fellow, University of North Carolina at
Chapel Hill, Chapel Hill, NC
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Courses Taught
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BIOL
4600 Senior Seminar
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BIOL
4199/5199 Molecular Biology
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BIOL
6040 Special Topics in Molecular Biology
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BIOL 6102/8102 Cell and Molecular
Biology
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BIOL 4601 Honors Seminar |
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BIOL 4700 Honors Research I |
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BIOL 4701 Honors Research II |
Student
Advising
- Coordinator, Honors in Biology
Summary of Research Projects
Dr.
Schrum's laboratory has ongoing collaborations with Dr. Mark
Clemens, Dr. Chris Yengo and Dr. Iain McKillop from the Department of Biology. Additionally,
Dr. Schrum also collaborates with Dr. Richard Rippe from the University
of North Carolina at Chapel Hill and Jenken Biosciences, Inc located
in the Research Triangle Park.
Hepatic fibrosis is characterized by an increase in type I collagen
deposition which alters the normal architecture of the liver leading
to liver dysfunction. Many etiologies have been associated with
hepatic fibrosis with chronic alcohol consumption being the leading
cause of liver fibrosis in the United States. The hepatic stellate
cell (HSC) is the primary cell type in the liver responsible for
excess synthesis of collagen during fibrosis. Following exposure to
alcohol, the HSC undergoes a transdifferentiation from a quiescent,
vitamin A storing cell to that of an activated, collagen producing myofibroblast-like cell. The effects of alcohol on the activation
of HSCs have been implicated to alcohol-induced oxidative stress.
The metabolism of ethanol leads to the production of free radicals
that have been linked to the development of alcohol-induced liver
injury. Thus, diminishing oxidative damage by the use of
antioxidants may serve as successful therapeutic treatments for
liver diseases caused by numerous agents including alcohol. S-adenosyl-L-methionine
(SAMe), the precursor of glutathione, has potential usefulness as an
antioxidant. SAMe has been shown to improve hepatic fibrosis;
however, the molecular mechanisms of SAMe in liver fibrosis is not
understood. The role of SAMe as an antioxidant implicates the redox-sensitive
transcription factor nuclear factor kappa B (NFkB)
and the pathway(s) that regulates its activity as being a key player
which may mediate the antioxidant effects of SAMe. SAMe’s
attenuation of liver fibrosis may occur through the regulation of
certain transcription factors that modulate collagen expression in
the HSC. Thus, we hypothesize that the antioxidant SAMe
inhibits alcohol-induced collagen expression by modulating NFkB
activity in the HSC. The results of these studies will aid in the
development of novel therapeutics aimed at preventing the
progression of oxidative-induced hepatic fibrosis.
My lab
is also interested in understanding the molecular mechanisms leading
to the transdifferentiation of the quiescent HSC to the
myofibroblast-like cell which is a key event in liver fibrosis.
We propose that as HSCs transdifferentiate, they require 2 separate
stimuli to become fully activated. An initial signal is needed to
dedifferentiate HSCs from the quiescent (Q) phenotype, and a second
signal is needed to differentiate the HSCs into the myofibroblastic
(MFB) phenotype. Ethanol and/or its metabolite acetaldehyde (AcCHO)
provide one of these signals. Understanding what signal causes these
cells to undergo transdifferentiation is a clear point of
intervention in cases of early, or even late hepatic fibrosis.
Further, understanding the detailed genetic expression associated
with the daily changes during the entire transdifferentiation
process will allow a greater ability to assess the effects of
various stimulants as well as provide more possible points for
intervention.
Dr.
Schrum also has an ongoing collaboration with Dr. Chris Yengo investigating the role
and expression profile of nonmuscle myosin II isoforms in
quiescent and activated hepatic stellate cells.
Regulation of
liver microcirculation is a complex system where blood flow is under
systemic and sinusoidal control. Under normal conditions, quiescent
hepatic stellate cells (HSCs) wrap around sinusoids to regulate
diameter, and thus blood flow, by contracting and dilating in
response to local vasoconstrictors and vasodilators. However,
activated HSCs exert a sustained contractile force, resulting in
hyper-constricted vessels. This leads to hepatic microcirculation
dysregulation, which contributes to the progression of diseases such
as fibrosis, hepatocellular carcinoma, or viral hepatitis.
We hypothesize that the hypercontractile property of
activated HSCs is associated with an increased isoform specific
expression of NMM II.
Additionally,
my lab along with Dr. Clemens has a collaboration with Jenkens
Biosciences, Inc. to investigate whether opioid compounds are
effective against inflammatory injury associated with fatty liver
and to determine the mechanism of action with particular interest in
HSC and kupffer cell activation.
Current
Grant Funding
"NFkB-mediated collagen regulation by
SAMe in HSCs" NIH/NIAA, NIH/NIAAA RO1 AA014891. Laura W. Schrum,
PI"Studies of a morphinan
derivative in the inflammatory injury associated with fatty liver",
Jenken Biosciences, Inc., Mark G. Clemens, PI; Laura W. Schrum,
Co-PI "Regulation of
sinusoidal perfusion in shock", NIH/NIDDK RO1 DK038201. Mark
Clemens, PI; Laura W. Schrum, CoI
Publications
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Tsukamoto
H, Wang SC, Ohata M, Schrum L, Rippe RA. 1998.
Expression of IL-10 by in vitro and in vivo activated
hepatic stellate cells. J. Biol. Chem. 273:302-308.
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Behrns
KE, Schrum LW, Que FG. 1999. Apoptosis:
cell death by proteolytic scalpel. Surgery. 126:463-468.
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Rippe RA, Schrum LW, Stefanovic B, Solis-Herruzo J, Brenner
DA. 1999. NF-kB inhibits transcription of the
a1(I)
collagen gene. DNA and Cell Biol. 18:751-761.
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Solís-Herruzo J, Rippe RA,
Schrum LW, de la Torre P, Garcia I, Jeffrey JJ, Munox-Yague
T, Brenner DA. 1999. Interleukin-6 increases rat metalloproteinase-13
gene expression through activation of AP1 transcription factor
in cultured fibroblasts. J. Biol. Chem. 274:30919-30926.
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Schrum LW, Rippe RA, Black D, Iimuro Y, Brenner DA, Behrns
KE. 2000. c-Jun does not mediate hepatocyte apoptosis
following NFkB inhibition and partial hepatectomy. J. Surg.
Res. 88:142-149.
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Lang A, Schrum LW, Schoonhoven R, Tuvia S, Solis-Herruzo
JA, Tsukamoto H, Brenner DA, Rippe RA. 2000. Expression
of the small heat shock protein
aB-Crystallin is induced following
activation of the hepatic stellate cell. Am. J. Physiol.
279:G1333-G1342.
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Miyahara
T, Schrum L, Rippe R, Xiong S, Yee H, Motomura K, Anania
F, Willson TM, Tsukamoto H. 2000. Peroxisome proliferator-activated
receptors and hepatic stellate cell activation. J. Biol.
Chem. 275:35715-35722.
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Schrum
LW, Bird MA, Olga S, Burchardt E-R, Grisham JW, Brenner DA,
Rippe RA, Behrns KE. 2001. Autocrine expression of
activated transforming growth factor-b1 induces apoptosis in normal
rat liver. Am. J. Physiol. 280:G139-G148.
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Bost
KL, Bento JL, Petty CC, Schrum LW, Hudson MC, Marriott
I. 2001. Monocyte chemoattractant protein-1 exression by
osteoblasts following infection with staphylococcus aureus
or salmonella. J. Interferon Cytokine Res. 21:297-304.
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Rivera
CA, Bradford BU, Hunt KJ, Adachi Y, Schrum LW, Koop DR,
Burchardt E-R, Rippe RA, Thurman RG. 2001. Attenuation of CCl4-induced
hepatic fibrosis by GdCl3 treatment or dietary glycine.
Am. J. Physiol. 281:G200-207.
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Faouzi
S, Burckhardt BE, Hanson JC, Campe CB, Schrum LW,
Rippe RA, Maher JJ. Anti-Fas induces hepatic chemokines and promotes
inflammation by an NF-kB-independent, caspase-3-dependent pathway.
J. Biol. Chem. 276:49077-49082.
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Gasper
NA, Petty CC, Schrum LW, Marriott I, Bost KL.
2002. Bacteria
induced CXCL10 secretion by osteoblasts can be mediated, in part,
through TLR-4. Infect. Immun. 70:4075-4082.
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Bird
MA, Lange PA, Schrum LW, Grisham JW, Rippe RA, Behrns KE.
2002. Cholestasis induces murine hepatocyte apoptosis and DNA
synthesis with preservation of the immediate-early gene response.
Surgery. 131:556-563.
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Samson CM, Schrum LW, Bird MA, Lange PA,
Brenner DA, Rippe RA, Behrns KE. 2002. Transforming growth factor-beta1 induces hepatocyte apoptosis
by a c-Jun independent mechanism. Surgery
132:441-449.
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Schrum
LW, Marriott I, Betsy Butler, Thomas EK, Hudson MC, Bost
KL. 2003. Functional CD40 expression induced following bacterial infection
of mouse and human osteoblasts. Infect. Immun.
71:1209-1216.
- Schrum LW, Bost KL, Hudson MC,
Marriott I. 2003. Bacterial infection induces expression of functional
MHC class II molecules in murine and human osteoblasts.
Bone 33:812-821.
- Black D, Bird MA, Samson CM, Lyman S,
Lange PA, Schrum LW, Qian T, Lemasters JJ, Brenner DA, Rippe
RA, Behrns KE .
2004. Primary cirrhotic hepatocytes resist TGFbeta-induced
apoptosis through a ROS-dependent mechanism. J. Hepatol. 40:942-951.
- Black D, Bird MA, Hayden M, Schrum
LW, Lange P, Samson C, Hatano E, Rippe RA, Brenner DA, Behrns KE.
2004. TNFalpha-induced hepatocyte apoptosis is associated with
alterations of the cell cycle and decreased stem loop binding protein.
Surgery 135:619-628.
- Gabele
E, Reif S, Tsukada S, Bataller R, Yata Y, Morris T, Schrum LW,
Rippe RA. 2005. Role of p70S6K in hepatic stellate cell
collagen gene expression and cell proliferation. J. Biol. Chem.
280:13374-13382.
- Merkel
SM, Kamoun W, Karaa A, Korneszczuk K, Schrum LW and Clemens MG.
2005. LPS Inhibits Endothelin-1-Mediated eNOS Translocation to the
Cell Membrane in Sinusoidal Endothelial Cells. Microcirculation.
12:433-442.
- McKillop I, Schrum LW. Alcohol
and liver cancer.
2005. Alcohol.
35:195-203.
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Zinchenko YS, Schrum LW, Clemens MG, Coger RN. 2006. Hepatocytes and Kupffer Cells Co-cultures on
Micropatterned Surfaces to Optimize Hepatocyte Function. Tiss. Eng.
12:751-761.
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Karaa A, Thompson KJ,
McKillop IH, Clemens MG, Schrum LW. S-adenosyl-L-methionine attenuates
oxidative stress and hepatic stellate cell activation in an
ethanol-LPS-induced fibrotic rat model. Shock. In press.
- Cross
BW, Gulledge AA, Anguita J, Schrum LW.
S-adenosyl-L-methionine (SAMe) increases IL-6 expression but inhibits IL-6-induced collagen
expression in hepatic stellate cells.
Submitted.
Current
Lab Members
Alyssa Gulledge, research assistant professor
Kyle
Thompson, doctoral student
Cathy Castellon Moore, doctoral
student
Stephani Day, masters student
Kaveh Daneshvar, rotating doctoral
student |
