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Laura Steel

Laura Steel, PhD

Associate Professor


Department: Microbiology & Immunology

Education

  • PhD - Cornell University (1977)

Laura Steel, PhD, is an associate professor in the Department of Microbiology & Immunology at Drexel University College of Medicine.

Research Interests

Disruptions to metabolic homeostasis in hepatitis B virus–infected hepatocytes; development of RNA silencing–based therapies for HBV

Research

The research in our laboratory is aimed at understanding how infection by hepatitis B virus (HBV) leads to disruptions in hepatocellular metabolic homeostasis that favor viral replication, but can lead to long-term damage, leaving the liver susceptible to the development of serious disease, including hepatocellular carcinoma (HCC).  We also have an interest in understanding the role the role of microRNAs (miRNAs) in shaping the outcome of viral infections. We have explored the use of miRNAs as antiviral therapeutics as well as the role of miRNAs in the interplay between viruses and their host cells in the course of an infection.

Our efforts originally focused on developing RNA silencing-based therapies for hepatitis B virus (HBV). Approximately 240 million people worldwide are chronically infected with HBV and therefore are at high risk for end-stage liver disease, including cirrhosis and hepatocellular carcinoma. Current therapies are inadequate in that they are often ineffective, can lead to the emergence of resistant viruses, or can be difficult for the patient to tolerate. Our laboratory has developed vectors that allow the simultaneous expression of multiple interfering RNAs that target viral transcripts. This is a strategy that maximizes efficacy against a broad range of viral genotypes while minimizing the potential for the emergence of escape mutants. We have developed a series of vectors to express miRNA-formatted interfering RNAs that target HBV transcripts, and our vectors have shown potent silencing of HBV targets in cell culture and animal models of HBV infection. We have applied similar principles of design in the development of silencing vectors that target HIV-1 RNAs and are inducible in HIV-1 infected cells.

Our laboratory is also investigating how HBV, and in particular the HBV regulatory protein HBx, can disrupt metabolic homeostasis in hepatocytes to favor HBV replication, but render the cells susceptible to long-term damage. Although HBV is regarded as a non-cytopathic virus, surprisingly little is known regarding how HBV infection can affect hepatocyte metabolic processes. Nevertheless, HBx is known to activate both mTORC1 and AMPK, which are key regulators of metabolic homeostasis. We are investigating the role of HBx in altering the sensitivity of the cellular response to regulators of mTORC1 and AMPK pathways and the importance of interactions between HBx and Lamtor-5 in mediating this response. We expect these studies will help to identify methods to prevent HBV-induced changes to metabolic homeostasis so as to slow or stop progressive cell damage and disease.  Future studies in this area could lead to the discovery of new targets for therapeutic intervention to prevent HBV replication and associated liver disease.

In the Media

Publications

Books and Book Chapters

Gene Transfer Methods: Introducing DNA into Living Cells and Organisms
Norton PA and LF Steel (eds.)
Eaton Publishing, Natick: 2000

"Polycistronic expression of interfering RNAs from RNA polymerase III promoters"
Steel LF and Sanghvi VR
In Functional Genomics, 2nd edition; Eds. M. Kaufmann and C. Klinger. Methods in Molec. Biol., 815: 347-359, 2011

Selected Publications (See all Laura Steel's publications in PubMed.)

"Intrinsic hepatocyte dedifferentiation is accompanied by upregulation of mesenchymal markers, protein sialylation and core alpha 1,6 linked fucosylation"
Mehta A, Comunale MA, Rawat S, Casciano JC, Lamontagne J, Herrera H, Ramanathan A, Betesh L, Wang M, Norton P, Steel LF, and Bouchard M
Scientific Reports 6:27965. PMID: PMC4481434, 2016

"Hepatitis B virus and microRNAs: complex interactions affecting hepatitis B virus replication and hepatitis B virus-associated diseases"  
Lamontagne J, Steel LF, and Bouchard MJ
World J Gastroenterol. 21:7375-99.  PMID: 26139985, 2015

"RNA silencing as a cellular defense against HIV-1 infection: progress and issues"
Sanghvi VR and LF Steel
FASEB J., 26: 3937-3945, Epub ahead of print Jul 2, 2012

"The cellular TAR RNA binding protein, TRBP, promotes HIV-1 replication primarily by inhibiting the activation of double-stranded RNA-dependent kinase PKR"
Sanghvi VR and LF Steel
J.Virol. 85: 12614-12621, 2011

"A re-examination of global suppression of RNA interference by HIV-1"
Sanghvi VR and Steel LF
PLoS One, 6(2): e17246, 2011

"Expression of interfering RNAs from an HIV-1 Tat-inducible chimeric promoter"
Sanghvi VR and Steel LF
Virus Research, 155: 106-111, 2010

"Multiple functional miRNAs can be produced from a single RNA polymerase III promoter"
Snyder LL, Ahmed I, and Steel LF
Nucleic Acids Research, 37: e127, 2009

"Vector design for liver-specific expression of multiple interfering RNAs that target hepatitis B virus transcripts"
Snyder LL, Esser JM, Pachuk CJ, and Steel LF
Antiviral Research, 80(1): 36-44, 2008

"GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma"
Marrero JA, Romano PR, Nikolaeva O, Steel L, Mehta A, Fimmel CJ, Comunale MA, D'Amelio A, Lok AS and Block TM
Journal of Hepatology, 43:1007-1012, 2005

"SELDI-TOF-MS profiling of serum for detection of the progression of cirrhotic hepatitis C disease to hepatocellular carcinoma"
Schwegler EE, Cazares L, Steel LF, Adam BA, Johnson DA, Semmes OJ, Block T, Marrero JA, and Drake RR
Journal of Hepatology, 41:634-642, 2005

"Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and people"
Block TM, Comunale MA, Lowman M, Steel LF, Romano PR, Fimmel C, Tennant BC, London WT, Evans AA, Blumberg BS, Dwek RA, Mattu TS, and Mehta AS
Proceedings from the National Academy of Sciences, 102:779-784, 2004

"Methods of comparative proteomic profiling for disease diagnosis"
Steel LF, Haab BB, and Hanash SM
Journal of Chromatography B, 815:275-284, 2004

"Comparative proteomic analysis of de-N-glycosylated serum from hepatitis B carriers reveals polypeptides that correlate with disease status"
Comunale MA, Mattu TS, Lowman M, Evans AA, London WT, Semmes, OJ, Ward M, Drake R, Romano PR, Steel LF, Block TM, and Mehta A
Proteomics, 4:826-838, 2004

"Efficient and specific removal of albumin from human serum samples"
Steel LF, Trotter MG, Nakajima, PB, Mattu, TS, Gonye G, and Block TM
Molecular & Cellular Proteomics, 2.4: 262-270, 2003

"A strategy for the comparative analysis of serum proteomes for the discovery of biomarkers for hepatocellular carcinoma"
Steel LF, Shumpert D, Trotter M, Seeholzer SH, Evans AA, London WT, Dwek R, and Block TM
Proteomics, 3:601-609, 2003

"A proteomic approach for the discovery of early detection markers of hepatocellular carcinoma"
Steel LF, Mattu TS, Mehta A, Hebestreit H, Dwek R, Evans A, London WT, and Block T
Disease Markers, 17:179-189, 2001

"Elements in the murine c-mos messenger RNA 5'-untranslated region repress translation of downstream coding sequences"
Steel LF, Telly DL, Leonard J, Rice BA, and Sawicki JA
Cell Growth & Differentiation, 7:1415-1424, 1996


Contact Information


Research Office

Department of Microbiology & Immunology
245 N. 15th Street
Philadelphia, PA 19102
Phone: 215.762.8621
Fax: 215.762.1479