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Nury Steuerwald

Nury M. Steuerwald, PhD
Director, Senior Research Scientist,  Molecular Biology Core Facility, Carolinas HealthCare System
Research Associate Professor, Biology Department, University of North Carolina at Charlotte
Director, Charlotte Genomics Consortium

Education

PhD: 1999, Florida International University (Miami)
BS : 1983, Florida International University

Research Interests

Dr. Steuerwald’s research interests have included quantitative expression analysis in single oocytes with particular emphasis on cell cycle regulation and checkpoint gene expression during meiosis. We hypothesized that altered gene expression may influence the capacity of the human oocyte to undergo accurate chromosome segregation during meiosis and may be a contributing factor in age-related aneuploidy. Initially, we focused on the expression of genes in the spindle assembly checkpoint pathway. This surveillance system is intended to guard against errors in chromosome alignment at the metaphase plate. Our work has demonstrated that checkpoint gene expression is reduced in oocytes from older women which may result in impaired monitoring mechanisms. Subsequent genome-wide analysis revealed that the expression of genes in several major functional categories are also affected by maternal age including those involved in cytoskeletal structure, mitochondrial function, stress responses, transcriptional regulation and protein trafficking.

Dr. Steuerwald and her colleagues at UNC Charlotte have also conducted experiments intended to elucidate the integrated mechanisms regulated by nitric oxide in early embryonic development. Nitric Oxide (NO) has well-documented effects on a variety of systems in both the adult and developing fetus, but the understanding of its role embryonic development is still rudimentary. NO is produced from L-arginine by the enzyme, nitric oxide synthase (NOS). Our studies demonstrated that three isoforms of NOS are expressed in murine embryos, and that NO regulates mitotic division in these embryos through at least one mechanism.

Under the direction of Dr. Steuerwald, the Clinical Translational Molecular Biology Research Laboratory has been engaged in a variety of projects aimed at investigating the molecular mechanisms underlying a variety of human diseases. In particular, the lab is examining the role of microRNAs (miRNAs) in the pathogenesis of various disease processes. MiRNAs are members of a class of small RNAs whose function is to regulate gene expression in organisms as diverse as animals, plants, and fungi. Many miRNAs are evolutionarily conserved and believed to play a role in controlling a variety of biological functions including developmental patterning, cell differentiation, cell proliferation, genome rearrangements and transcription regulation. In collaboration with Mark Clemens, PhD, in the Biology Department at UNCC, the lab is investigating the role of miRNAs in altered hepatic blood flow regulation during experimental sepsis.  Together with Dr. Herbert Bonkovsky, we are delineating circulating miRNA profiles in drug induced liver injury (DILI) to determine if a characteristic signature exists. We have also examined the global expression profile of miRNAs in the liver under normal and pathological conditions. The lab has teamed with Drs. David Sindram and William Ahrens to examine global changes in miRNA expression in archival malignant pancreatic tissue samples.

Dr. Steuerwald has collaborated with Drs. Bonkovsky, Foureau and Norton to examine the cytokine profiles in sera in order to determine whether a signature exist that predicts poor or good outcomes in DILI.  They found that DILI is associated with variable immune responses which appear to be of prognostic, and perhaps, diagnostic significance.

Dr. Steuerwald’s lab is also involved with several genomic profiling studies employing Next Generation Sequencing (NGS). NGS parallelizes the sequencing process thereby producing millions of sequences simultaneously. With this technology, we are able to globally investigate disease mechanisms including DNA sequence variants, RNA expression levels, and promoter methylation status on a high resolution sequencing platform. High-throughput sequencing has been employed to identify unknown causative mutations in human disease, and this technology will likely impact our understanding of complex disease trait loci and pharmacogenomics. Dr. Steuerwald is collaborating with clinical investigators using this technology in the Liver, Digestive, and Metabolic Disorders Laboratory, the McColl-Lockwood Laboratory for Muscular Dystrophy, the Levine Cancer Institute, UNCC and others.

 

Recent Publications

Allie G, Causby S, Matthews ML, Usadi RS, Steuerwald N, Hurst BS, Marshburn P. The Influence of Ejaculatory Abstinence on Oxidative Stress in Semen:  A Mechanism that May Explain Improved Pregnancy Rates after Intrauterine Insemination. Fertil Steril [In Press].

Gruber H, Sha W, Brouwer C, Steuerwald N, Hoelscher G, Hanley E. A Novel Catechol-O-Methyltransferase Variant Associated with Human Disc Degeneration. Int J Med Sci. 2014;11(7):748-53. PMCID: PMC4045795

Amin H, Vachris J, Hamilton A, Steuerwald N, Howden R, Tsvitse S. GSK3ß inhibition and LEF1 upregulation in skeletal muscle following a bout of downhill running. J Physiol Sci. 2014 Jan;64(1):1-11. Epub 2013 Aug 21.

Steuerwald N, Foureau DM Norton HJ, Zhou J, Parsons JC, Chalasani N, Fontana RJ, Watkins PB, Lee WM, Redde KR, Stolz A, Talwalkar J, Davern T, Saha D, Bell LN, Barnhart H, Gu J, Serrano J, Bonkovsky HL. Profiles of Serum Cytokines in Acute Drug-Induced Liver Injury and Their Prognostic Significance. PLoS One. 2013 Dec 27;8(12). DOI: 10.1371/journal.pone.0081974

Fargnoli AS, Katz MG, Yarnall C, Isidro A, Petrov M, Steuerwald N, Ghosh S, Richardville KC, Hillesheim R, Williams RD, Kohlbrenner E, Stedman HH, Hajjar RJ, Bridges CR. Cardiac Surgical Delivery of the Sarcoplasmic Reticulum Calcium ATPase Rescues Myocytes in Ischemic Heart Failure. Ann Thorac Surg 2013 Aug;96(2):586-95. PMCID: PMC3735816

Larion S, Hwang S, Lee JG, Rossman W, Vachris J, Steuerwald N, Li T, Maddukuri V, Groseclose G, Finkielstein C, Bonkovsky HL. Circadian rhythms in acute intermittent porphyria--a pilot study. Eur J Clin Invest 2013 Jul;43(7):727-39.  PMID: 23650938

Bonkovsky HL, Hou W, Steuerwald N, Tian Q, Li T, Parsons J, Hamilton A, Hwang S, Schrum L.  Heme status affects human hepatic mRNA and miRNA expression. World J Gastroenterol 2013 Mar 14;19(10):1593-601. PMCID: PMC3602476

Hou W, Tian Q, Steuerwald NM, Schrum LW, Bonkovsky HL. The let-7 microRNA enhances heme oxygenase-1 by suppressing Bach1 and attenuates oxidant injury in human hepatocytes. Biochim Biophys Acta. 2012; 1819(11-12):1113-22. PMCID: PMC3480558

Lakner AM, Steuerwald NM, Walling TL, McKillop IH, Russo MW, Bonkovsky HL, Schrum LW. Inhibitory Effects of microRNA 19b in Hepatic Stellate Cell-Mediated Fibrogenesis. 2012 Jul;56(1):300-10. PMCID: PMC3342471

Ellefson WM, Lakner AM, Hamilton A, McKillop IH, Bonkovsky HL, Steuerwald NM, Huet YM, Schrum LW. Neonatal androgenization exacerbates alcohol-induced liver injury in adult rats, an effect abrogated by estrogen. PLoS One. 2011;6(12).  PMCID: PMC3243688

Mehrab-Mohseni M, Sendi H, Steuerwald N, Ghosh S, Schrum L, Bonkovksy HL. Legalon-SIL Down-regulates HCV Core and NS5A Expression in Human Hepatoma Cell Lines Expressing Full-length HCV. World J Gastroenterol. 2011;17(13):1694-1700. PMCID: PMC3072633

Panov A, Steuerwald NM, Vavilin V, Dambinova S, Bonkovsky HL. Role of Neuronal Mitochondrial Metabolic Phenotype in Pathogenesis of ALS. In: Amyotrophic Lateral Sclerosis. Maurer, M (Ed). University Campus STeP Ri; Rijeka, Croatia, 2011.

Steuerwald NM, Parsons J, Bennett K, Bates T, Bonkovsky HL. Parallel miRNA and mRNA expression profiling of (genotype 1b) human hepatoma cells expressing HCV. Liver Int. 2010 Liver Int. 2010 Nov;30(10):1490-504. PMID: 20825557

Fokin AA, Steuerwald NM, Ahrens WA, Allen KE. Anatomical, histologic, and genetic characteristics of congenital chest wall deformities. Semin Thorac Cardiovasc Surg. 2009;21(1):44-57. PMID: 19632563

Steuerwald N, Bermúdez MG, Wells D, Munné S, Cohen J. Maternal age-related differential global expression profiles observed in human oocytes. Reprod Biomed Online  2007;14: 700-708. PMID: 17579982

Steuerwald, N. Gene Expression Analysis in the Human Oocyte and Embryo. In: Human Preimplantation Embryo Selection. Informa Healthcare, London, England. 2007. pp 263-274.

Steuerwald N, Steuerwald MD, Mailhes JB. Post-ovulatory aging of mouse oocytes leads to decreased MAD2 transcripts and increased frequencies of premature centromere separation and anaphase. Mol Hum Reprod 2005; 11: 623-630. PMID: 16207798

Steuerwald N. Meiotic checkpoints for assessment of aneuploid gametes.  Cytogenet Genome Res 2005; 111: 256-259. PMID: 16192702

Bermudez, MG, Wells D, Malter H, Munne S, Cohen J, Steuerwald N. Expression profiles of individual human oocytes using microarray technology. Reprod Biomed Online 2004; 8: 325-337. PMID: 15038899

Current, Recent and Pending Grant Support

Ancillary Study Title: Extention and Validation of Profiles
Funding Agency: National Institutes of Health (U01-DK065176-07)
Role: Co- Investigator (PI: Rochon J)
Years: 2014-2015
The aim of this study is to examine the chemokine/cytokine profiles in sera of selected subjects with acute DILI or other causes of acute liver injury and perform staining of liver biopsies with dual stains for infiltrating leukocytes to serve as validation of previously conducted pilot studies.

Pending

Grant Title: Effect of heme on mRNA and miRNA profiles
Funding Agency: National Institutes of Health (1R15 HL117199-01)
Role: Co- Investigator (PI: Bonkovsky HL)
Years: 2013-2015
The goal of this research is to determine the pathways and mechanisms whereby heme affects levels of mRNAs and miRNAs that modulate expression of key enzymes in heme metabolism.

Grant Title: Hydrogen sulfide and miRNA interaction during experimental sepsis in vitro
Funding Agency: CMC-UNCC Collaborative Grants Program
Role: Co-Principal Investigator  (Co-PI: Clemens M)
Years: 2012-2013
The goal of this project is to examine the effect of H2S, hypoxia, and endotoxemia on miRNA expression in mouse sinusoidal endothelial cells

Ancillary Study Title: Pilot study to delineate miRNA profiles and their correlation with clinical features in DILI
Funding Agency: National Institutes of Health (U01-DK065176-07)
Role: Co-Principal  Investigator (Co-PI: Rochon J)
Years: 2011-2012
The aim of this study is to examine the miRNA profiles in sera and urine from selected subjects enrolled in the prospective DILIN protocol in order to see determine whether a signature exists that is predictive of DILI outcome

Title: Pilot study of Circadian rhythms of serum cortisol and melatonin and clock gene expression in whole blood leukocytes of subjects with biochemically active acute porphyria.
Funding Agency: Carolinas Healthcare Foundation
Role: Co- Investigator (PI: Caballes FR)
Years: 2011-2012
The aim of this proposal is to clearly define the circadian rhythms and patterns of serum cortisol and melatonin as well as to define the circadian rhythms and patterns of levels of expression of selected molecular clock genes and key genes involved in heme metabolism in controls and subjects with acute intermittent porphyria. 

Title: Modulation of Disc Cell Gene Expression by Coculture with Adipose-Derived Stem Cells.
Funding Agency: Carolinas Healthcare Foundation
Role: Co-Investigator (PI: Gruber H)
Years: 2010-2011
The aim of this proposal is to investigate the effect of human adipose-derived mesenchymal stem cells on disc cell matrix production by growing human disc cells and stem cells in coculture. 

Ancillary Study Title: Pilot study to delineate chemokine/cytokine profiles and their correlation with clinical features in DILI
Funding Agency: National Institutes of Health (U01-DK065176-07)
Role: Co-Principal Investigator (PI: Rochon J)
Years: 2010-2011
The aim of this study is to examine the chemokine/cytokine profiles in sera from selected subjects enrolled in the prospective DILIN protocol in order to see whether there are profiles that portend bad or good outcomes of DILI

Title: Regulation of Hepatic Heme Metabolism
Funding Agency: National Institutes of Health (5R01DK038825-23)
Role: Co- Investigator (PI: Bonkovsky HL)
Years: 1987-2011
The long-term goal of this research program is to understand the pathways and regulation of hepatic porphyrin and heme metabolism.

Grant Title: Is there an Association Between the Presence of Human Papillomavirus (HPV) Infection and PPROM Delivery
Funding Agency: Carolinas Healthcare Foundation
Role: Co-Investigator (PI: Kalleberg K)
Years: 2010-2011
The aim of this proposal is to determine if there are certain identifiable types of human papillomavirus that are present more often in women with preterm premature rupture of membranes (PPROM) when compared to women with normal onset of term labor.

Grant Title: The Influence of Ejaculatory Abstinence on Oxidative Stress in Semen
Funding Agency: Carolinas Healthcare Foundation
Role: Co- Investigator (PI: Giddings A)
Years: 2009-2010
The specific goal of this proposal is to determine whether the period of ejaculatory abstinence (EA) influences the total antioxidant capacity (TAC) of semen or impacts lipid peroxidation (LPO) of sperm membranes, the latter a measure of reactive oxygen species damage.

Title: Gender and sex steroid hormone effects on developmentally-induced responses in ALD
Funding Agency: Carolinas Healthcare Foundation
Role: Principal Investigator
Years: 2009-2010
The specific goal of this proposal is to determine if the injurious effect of estrogen in alcohol-exposed females is due solely to adult exposure to estrogen or in part to the effects of estrogen on a female imprinted liver.

 

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