Julius O. Nyalwidhe, PhD

Teaching:

Education:

	Tanya C. Burch, Ph.D. Postdoc Ph.D. - University of North Carolina Chapel Hill, NC
	Megan T. Watson, B.S., Research Technician B.S. - Virginia Tech Blacksburg, VA

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Mechanisms of Cancer Pathogenesis
Dr. Nyalwidhe’s laboratory focuses on molecular biology, functional genomics and proteomic approaches to study cancer for the purposes of understanding cancer biology as well as to discover clinical biomarkers. The focus is on understanding the molecular events and signaling mechanisms that are involved in cancer progression and disease severity. The objective is to identify and disrupt signaling mechanisms that are involved in cancer progression and severity. The molecules that are involved in these mechanisms are potential diagnostic and prognostic biomarkers for disease and may also provide avenues for targeted cancer drug development. The emphasis is on mechanisms and targets that could explain cancer health disparities between different ethnic groups. Our recent research findings demonstrate the differential regulation of proteins and that their glycosylation patterns closely correlate with prostate cancer disease severity. We are also interested in determining the mechanisms of chemopreventive action of nutraceuticals against cancers. The objective is to identify and characterize the molecular targets and mechanisms of action of known nutraceuticals involved in cancer prevention.

 

Glycosylation and Cancer
Protein glycosylation plays a central role in mediating protein stability, function, and structure and the modulation of signal transduction pathways that drive carcinogenesis and progression to aggressive disease. The focus is on understanding the role of protein glycosylation in the development of aggressive forms of prostate and other cancers. Changes in glycosylation patterns are of great significance, as these may influence many cellular processes including cell adhesion, signaling, and stabilization of protein structure, protein trafficking, as well as oncogenesis. Aberrant glycosylation of glycoproteins has been observed in many malignancies, and these changes influence disease progression. Most known cancer biomarkers from bodily fluids that are currently utilized in the clinic are glycoproteins. We and others have demonstrated differential expression of glycans in PSA and PAP that correlate with disease severity. Our current focus is to utilize new generation high resolution, high mass accuracy and high sensitivity mass spectrometry instruments with high data acquisition speeds and flexibility in combining multiple stages of higher energy fragmentation techniques collision dissociation (HCD) with ion trap collision induced dissociation (CID) and electron transfer dissociation (ETD) for glycomic characterization. This has provided us with the opportunity to develop innovative multimode MS2/MS3 data acquisition and processing methods that best address the most relevant and challenging issues that have been associated LC/MS based glycomic analyses. We are currently using these methods for qualitative and quantitative analysis of potential biomarker targets of prostate cancer in clinical samples.

Mechanisms of Host pathogen Interactions
The focus of this project is on understanding the mechanisms of interactions between infectious pathogens and their host cells. A major research focus is the human malaria parasite Plasmodium falciparum, which invades and develops in red blood cells to cause disease pathologies that include severe malarial anemia, nephropathy and cerebral disease. The goal is to define unique and fundamental pathways and mechanisms in the microorganisms as well as human cells that provide molecular insights, targets and therapies in neglected diseases. Additionally, we are also focusing on understanding the mechanisms of pathogenesis of a variety of other infectious agents, and viral-induced carcinomas. The emphasis is on the application of molecular biology, functional and structural proteomics and mass spectrometry techniques to functionally characterize protein post-translational modifications to determine their influence in the progression and outcome of disease.

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• Kim Y, Jeon J, Mejia S, Yao CQ, Ignatchenko V, Nyalwidhe JO, Gramolini AO, Lance RS, Troyer DA, Drake RR, Boutros PC, Semmes OJ, Kislinger T. Targeted proteomics
  
  identifies liquid-biopsy signatures for extracapsular prostate cancer. Nature communications. 2016; 7:11906. PMID: 27350604.
• Yang L, Dutta SM, Troyer DA, Lin JB, Lance RA, Nyalwidhe JO, Drake RR, Semmes OJ.
  Dysregulated expression of cell surface glycoprotein CDCP1 in prostate cancer
  Oncotarget. 2015. 6(41):43743-58. PMID: 26497208.
  
  
• Burch TC, Isaac G, Booher CL, Rhim JS, Rainville P, Langridge J, Baker A, Nyalwidhe JO.
  Comparative Metabolomic and Lipidomic Analysis of Phenotype Stratified Prostate Cells.
  PLoS One. 2015. 10(8):e0134206. PMID: 26244785.

• Drake RR, Jones EE, Powers TW, Nyalwidhe JO.
  Altered glycosylation in prostate cancer. Adv Cancer Res. 2015. PMID: 25727153.

• Nyalwidhe JO, Betesh LR, Powers TW, Jones EE, White KY, Burch TC, Brooks J, Watson MT, Lance RS, Troyer DA, Semmes OJ, Mehta A, Drake RR.
  Increased Bisecting N-Acetylglucosamine and Decreased Branched Chain Glycans of N-linked Glycoproteins in Expressed Prostatic Secretions Associated with Prostate Cancer Progression.
  Proteomics Clin Appl. 2013. doi: 10.1002/prca.201200134. PMID: 23775902.
  
  
• Burch TC, Watson MT, Nyalwidhe JO.
  Variable metastatic potentials correlate with differential plectin and vimentin expression in syngeneic androgen independent prostate cancer cells.
  PLoS One. 2013. 8(5):e65005. PMID: 23717685.
  
  
• Principe S, Jones EE, Kim Y, Sinha A, Nyalwidhe JO, Brooks J, Semmes OJ, Troyer DA, Lance RS, Kislinger T, Drake RR.
  In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
  Proteomics. 2013. 13(10-11):1667-71. PMID: 23533145.
  
  
• Nyalwidhe J, Burch T, Bocca S, Cazares L, Green-Mitchell S, Cooke M, Birdsall P, Basu G, Semmes OJ, Oehninger S.
  The search for biomarkers of human embryo developmental potential in IVF: a comprehensive proteomic approach.
  Mol Hum Reprod. 2013, 19(4):250-63. PMID: 23247814.
  
  
• Kim Y, Ignatchenko V, Yao CQ, Kalatskaya I, Nyalwidhe JO, Lance RS, Gramolini AO, Troyer DA, Stein LD, Boutros PC, Medin JA, Semmes OJ, Drake RR, Kislinger T.
  Identification of differentially expressed proteins in direct expressed prostatic secretions of men with organ-confined versus extracapsular prostate cancer.
  Mol Cell Proteomics. 2012, 11(12):1870-84. PMID: 22986220.
  
  
• Sharp JA, Echague CG, Hair PS, Ward MD, Nyalwidhe JO, Geoghegan JA, Foster TJ, Cunnion KM.
  Staphylococcus aureus surface protein SdrE binds complement regulator factor H as an immune evasion tactic.
  PLoS One. 2012, 7(5):e38407. PMID: 22675461.
  
  
• Hair PS, Echague CG, Rohn RD, Krishna NK, Nyalwidhe JO, Cunnion KM.
  Hyperglycemic conditions inhibit C3-mediated immunologic control of Staphylococcus aureus.
  J Transl Med. 2012, 5:10:35. PMID: 22390383.
  
  
• Principe S, Kim Y, Fontana S, Ignatchenko V, Nyalwidhe JO, Lance RS, Troyer DA, Alessandro R, Semmes OJ, Kislinger T, Drake RR, Medin JA.
  Identification of prostate-enriched proteins by in-depth proteomic analyses of expressed prostatic secretions in urine.
  J Proteome Res. 2012,11(4):2386-96. PMID: 22339264.
  
  
• Hair PS, Wagner SM, Friederich PT, Drake RR, Nyalwidhe JO, Cunnion KM.
  Complement regulator C4BP binds to Staphylococcus aureus and decreases opsonization.
  Mol Immunol. 2012, 50(4):253-61. PMID: 22333221.
  
  
• Green-Mitchell SM, Cazares LH, Semmes OJ, Nadler JL, Nyalwidhe JO.
  On-tissue identification of insulin: in situ reduction coupled with mass spectrometry imaging.
  Proteomics Clin Appl. 2011, 5(7-8):448-53. PMID: 21656913.
  
  
• Fernandez Falcon MF, Echague CG, Hair PS, Nyalwidhe JO, Cunnion KM.
  Protease inhibitors decrease IgG shedding from Staphylococcus aureus, increasing complement activation and phagocytosis efficiency.
  J Med Microbiol. 2011, 60(Pt 10):1415-22. PMID: 21636671.
  
  
• Yang L, Nyalwidhe JO, Guo S, Drake RR, Semmes OJ.
  Targeted identification of metastasis-associated cell-surface sialoglycoproteins in prostate cancer.
  Mol Cell Proteomics. 2011, 10(6):M110.007294. PMID: 21447706.
  
  
• Gatlin CL, White KY, Tracy MB, Wilkins CE, Semmes OJ, Nyalwidhe JO, Drake RR, Malyarenko DI.
  Enhancement in MALDI-TOF MS analysis of the low molecular weight human serum proteome.
  J Mass Spectrom. 2011, 46(1):85-9. PMID: 21190259.
  
  
• Belgnaoui SM, Fryrear KA, Nyalwidhe JO, Guo X, Semmes OJ.
  The viral oncoprotein tax sequesters DNA damage response factors by tethering MDC1 to chromatin.
  J Biol Chem. 2010, 285(43):32897-905. PMID: 20729195.
  
  
• Gronemus JQ, Hair PS, Crawford KB, Nyalwidhe JO, Cunnion KM, Krishna NK.
  Potent inhibition of the classical pathway of complement by a novel C1q-binding peptide derived from the human astrovirus coat protein.
  Mol Immunol. 2010, 48(1-3):305-13. PMID: 20728940.
  
  
• Guo X, Ward MD, Tiedebohl JB, Oden YM, Nyalwidhe JO, Semmes OJ.
  Interdependent phosphorylation within the kinase domain T-loop Regulates CHK2 activity.
  J Biol Chem. 2010, 285(43):33348-57. PMID: 20713355.
  
  
• Azimzadeh O, Sow C, Gèze M, Nyalwidhe JO, Florent I.
  Plasmodium falciparum PfA-M1 aminopeptidase is trafficked via the parasitophorous vacuole and marginally delivered to the food vacuole.
  Malar J. 2010, 30; 9:189. PMID: 20591164.
  
  
• Drake RR, Elschenbroich S, Lopez-Perez O, Kim Y, Ignatchenko V, Ignatchenko A, Nyalwidhe JO, Basu G, Wilkins CE, Gjurich B, Lance RS, Semmes OJ, Medin JA, Kislinger T.
  In-depth proteomic analyses of direct expressed prostatic secretions.
  J Proteome Res. 2010, 9(5):2109-16. PMID: 20334419.
  
  
• Chao TC, Kalinowski J, Nyalwidhe J, Hansmeier N.
  Comprehensive proteome profiling of the Fe(III)-reducing myxobacterium Anaeromyxobacter dehalogenans 2CP-C during growth with fumarate and ferric citrate.
  Proteomics. 2010, 10(8):1673-84. PMID: 20162560.
  
  
• Britten RA, Mitchell S, Johnson AM, Singletary SJ, Keeney SK, Nyalwidhe JO, Karbassi ID, Lonart G, Sanford LD, Drake RR.
  The identification of serum biomarkers of high-let radiation exposure and biological sequelae.
  Health Phys. 2010, 98(2):196-203. PMID: 20065683.
  
  
• Cazares LH, Troyer D, Mendrinos S, Lance RA, Nyalwidhe JO, Beydoun HA, Clements MA, Drake RR, Semmes OJ.
  Imaging mass spectrometry of a specific fragment of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 2 discriminates cancer from uninvolved prostate tissue.
  Clin Cancer Res. 2009, 15(17):5541-51. PMID: 19690195.
  
  
• Karbassi ID, Nyalwidhe JO, Wilkins CE, Cazares LH, Lance RS, Semmes OJ, Drake RR.
  Proteomic expression profiling and identification of serum proteins using trypsin beads with MALDI-TOF/TOF.
  J Proteome Res. 2009, 8(9):4182-92. PMID: 19603828.
  
  
• Schaub NP, Jones KJ, Nyalwidhe JO, Cazares LH, Karbassi ID, Semmes OJ, Feliberti EC, Perry RR, Drake RR.
  Serum proteomic biomarker discovery reflective of stage and obesity in breast cancer patients.
  J Am Coll Surg. 2009, 208(5):970-8; discussion 978-80. PMID: 19476873.
  
  
• Drake RR, White KY, Fuller TW, Igwe E, Clements MA, Nyalwidhe JO, Given RW, Lance RS, Semmes OJ.
  Clinical collection and protein properties of expressed prostatic secretions as a source for biomarkers of prostatic disease.
  J Proteomics. 2009, 72(6):907-17. PMID: 19457353.
  
  
• White KY, Rodemich L, Nyalwidhe JO, Comunale MA, Clements MA, Lance RS, Schellhammer PF, Mehta AS, Semmes OJ, Drake RR.
  Glycomic characterization of prostate-specific antigen and prostatic acid phosphatase in prostate cancer and benign disease seminal plasma fluids.
  J Proteome Res. 2009, 8(2):620-30. PMID: 19128049.
  
  
• Bolte K, Kawach O, Prechtl J, Gruenheit N, Nyalwidhe J, Maier UG.
  Complementation of a phycocyanin-bilin lyase from Synechocystis sp. PCC 6803 with a nucleomorph-encoded open reading frame from the cryptophyte Guillardia theta.
  BMC Plant Biol. 2008, 6; 8:56. PMID: 18485196.
  
  
• Jones D, Nyalwidhe J, Tetley L, Barrett MP.
  McArthur revisited: fluorescence microscopes for field diagnostics.
  Trends Parasitol. 2007, 23(10):468-9. PMID: 17826338.
  
  
• Azim-Zadeh O, Hillebrecht A, Linne U, Marahiel MA, Klebe G, Lingelbach K, Nyalwidhe J.
  Use of biotin derivatives to probe conformational changes in proteins.
  J Biol Chem. 2007, 282(30):21609-17. PMID: 17545162.
  
  
• Shamseldin A, Nyalwidhe J, Werner D.
  A proteomic approach towards the analysis of salt tolerance in Rhizobium etli and Sinorhizobium meliloti strains.
  Curr Microbiol. 2006 52(5):333-9. PMID: 16604415.
  
  
• Nyalwidhe J, Lingelbach K.
  Proteases and chaperones are the most abundant proteins in the parasitophorous vacuole of Plasmodium falciparum-infected erythrocytes.
  Proteomics. 2006, 6(5):1563-73. PMID: 16470785.
  
  
• Nyalwidhe J, Maier UG, Lingelbach K.
  Intracellular parasitism: cell biological adaptations of parasitic protozoa to a life inside cells.
  Zoology (Jena). 2003,106(4):341-8. PMID: 16351918.
  
  
• Baumeister S, Endermann T, Charpian S, Nyalwidhe J, Duranton C, Huber S, Kirk K, Lang F, Lingelbach K.
  A biotin derivative blocks parasite induced novel permeation pathways in Plasmodium falciparum-infected erythrocytes.
  Mol Biochem Parasitol. 2003 132(1):35-45. PMID: 14563535.
  
  
• Nyalwidhe J, Baumeister S, Hibbs AR, Tawill S, Papakrivos J, Volker U, Lingelbach K.
  A nonpermeant biotin derivative gains access to the parasitophorous vacuole in Plasmodium falciparum-infected erythrocytes permeabilized with streptolysin O.
  J Biol Chem. 2002, 18;277(42):40005-1. PMID: 12186876.
  
  
• Khan B, Omar S, Kanyara JN, Warren-Perry M, Nyalwidhe J, Peterson DS, Wellems T, Kaniaru S, Gitonga J, Mulaa FJ, Koech DK.
  Antifolate drug resistance and point mutations in Plasmodium falciparum in Kenya.
  Trans R Soc Trop Med Hyg. 1997, (4):456-60. PMID: 9373654.
  
  

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