Associate Professor / Honors Coordinator

Molecular mechanisms of liver fibrosis.

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
• 2001-2007 Assistant Professor, University of North Carolina at Charlotte, Charlotte, NC
• 2000-2001 Research Assistant Professor, University of North Carolina at Charlotte, Charlotte, NC
• 1997-2000 Research Analyst, University of North Carolina at Chapel Hill, Chapel Hill, NC
• 1993-1997 Postdoctoral Fellow, University of North Carolina at Chapel Hill, Chapel Hill, NC

Courses Taught

• BIOL 4600 Senior Seminar
• BIOL 4199/5199 Molecular Biology
• BIOL 6040 Special Topics in Molecular Biology
• BIOL 6102/8102 Cell and Molecular Biology
• BIOL 4601 Honors Seminar
• BIOL 4700 Honors Research I
• 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 and Dr. Chris Yengo from the Department of Biology and Dr. Iain McKillop from Carolinas Medical Center. 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, Co-I
• "Effect of alcohol on hepatocellular carcinoma progression in vivo", NIH/NIAAA R21 AA016858. Iain McKillop, PI; Laura W. Schrum, Co-I.

Publications

• 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.
• Behrns KE, Schrum LW, Que FG. 1999. Apoptosis: cell death by proteolytic scalpel. Surgery. 126:463-468.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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 p70^S6K 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.
• 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.
• Karaa A, Thompson KJ, McKillop IH, Clemens MG, Schrum LW. 2008. S-adenosyl-L-methionine attenuates oxidative stress and hepatic stellate cell activation in an ethanol-LPS-induced fibrotic rat model. Shock 30:197-205.
• Zheng J, Tian Q, Hou W, Watts JA, Schrum LW, Bonkovsky HL. 2008. Tissue-specific expression of ALA synthase-1 and heme oxygenase-1 and their expression in livers of rats chronically exposed to ethanol. FEBS Lett. 582:1829-1834.
• McKillop IH, Schrum LW. Hepatic ethanol metabolism. In Schwab M (ed): Encylopedia of Cancer. Springer, In press.

Current Lab Members

• Cathy Castellon Moore, doctoral student
• Ashley Lakner, doctoral student
• Kyle Thompson, doctoral student

Former Lab Members

• Amel Karaa, MD (Postdoctoral fellow) - Residency at Mt. Auburn Hospital (Harvard Medical School Affiliate)
• Alyssa Gulledge, PhD (Research Assistant Professor) - Research Associate, NC Research Campus
• Brian Cross (MS student) - St. Louis University Medical School, Residency at Emory University
• Stephani Day (MS student) - Lab Director, Cleveland Clinic
• Kavita Pal (honors undergraduate) - Medical School
• Alexandra Yarborough (honors undergraduate) - UNC-Chapel Hill Dental School
• Anthony Fowler (honors undergraduate) - Graduate School (Chemistry) UNC Charlotte