Nury M. Steuerwald, PhD
PhD: 1999, Florida International University (Miami) BS : 1983, Florida International University
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.
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: Extension and Validation of Profiles
Grant Title: Effect of heme on mRNA and miRNA profiles
Grant Title: Hydrogen sulfide and miRNA interaction during experimental sepsis in vitro
Ancillary Study Title: Pilot study to delineate miRNA profiles and their correlation with clinical features in DILI
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.
Title: Modulation of Disc Cell Gene Expression by Coculture with Adipose-Derived Stem Cells.
Ancillary Study Title: Pilot study to delineate chemokine/cytokine profiles and their correlation with clinical features in DILI
Title: Regulation of Hepatic Heme Metabolism
Grant Title: Is there an Association Between the Presence of Human Papillomavirus (HPV) Infection and PPROM Delivery
Grant Title: The Influence of Ejaculatory Abstinence on Oxidative Stress in Semen
Title: Gender and sex steroid hormone effects on developmentally-induced responses in ALD