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YuanPu Peter Di, PhD

Associate Professor, Environmental and Occupational Health

Contact

100 Technology Dr, 322 BRIDG 15219
R-znvy: crgreqv@cvgg.rqh
Primary Phone: 967-179-3263
Secondary Phone: 967-179-3934
Fax: 967-179-4816
Web site:


Personal Statement

Our laboratory is interested in investigating effects of environmental stress such as toxic chemicals and microorganisms on airway epithelial cell differentiation and lung diseases. One of our current research projects is focused on elucidating the molecular mechanisms that regulate the interaction between airway epithelial cells and exposure to environmental insults such as TCDD and tobacco smoke. We are also interested in how environmental agents affect host defense mechanism, especially airway secretion and infection, that relates to pulmonary disease. The ultimate goal of our laboratory is to develop new potential biomarkers for early detection of pre-neoplastic lesions that is caused by environmental exposure, as well as for the development of novel treatment strategies against toxicant-induced respiratory pathogenesis. The continuous cell layer of the respiratory epithelium acts as a protective physical barrier against inhaled agents. It also plays a key role in other airway related mechanisms such as inflammatory reactions, immune responses, mucociliary clearance, neurogenic regulation, and anti-infectious secretion. It is known that environmental stress can contribute to various diseases of the respiratory tract, and we are specifically interested in how the respiratory tract copes with these insults. Our laboratory has identified a serous cell type- and airway- specific novel gene, spurt(secretory protein in upper respiratory tracts), through the cDNA microarray system. We have demonstrated in previous studies that this gene responds swiftly and significantly to several environmental stimuli; such as ozone and tobacco smoke exposure. Bioinformatic analyses and characterizing experiments suggest that spurt is a novel secretory protein, and we have observed that spurt is secreted into the human airway lumen. Spurt secretion is increased in sputum from patients with chronic obstructive pulmonary disease (COPD) and asthma, while it is significantly decreased in the sputum of cystic fibrosis (CF) patients. Of potential significance, we have also observed bactericidal activity of spurt's gene product. Because environmental pollution and airway bacterial infection have been associated with various lung diseases, we are particularly interested in understanding the mechanisms of spurt's airway-specific bactericidal activity in the host defense response after environmental insults. Additionally, several other genes that relate to specific Th1/Th2 immune response or innate immunity are also being investigated for their roles in environmental exposure related respiratory diseases. The research focus of our laboratory is to elucidate the mechanisms of airway pathogenesis due to environmental toxin exposure. In particular, we are trying to explore the genetic variances that contribute to individual susceptibility to lung injury and airway disease. Therefore, our secondary area of research is focused on elucidating the regulatory mechanism and gene expression profiling of toxic exposure- and oxidant-induced respiratory pathogenesis. We are currently using several approaches including transgenic and knockout mouse, microarray, genomics, proteomics, and metabonomics methods to identify a cluster of genes and/or transcriptional factors that could represent the major contributing factors to environmental exposure induced lung diseases.


Education

1986     National Defense Medical Center     Medicine     Certificate      

1995     SUNY at Buffalo (Roswell Park Div.)     Biophysics     Ph.D.              

1999     University of California at Davis     Innovation & Tech. Mgt     M.B.A.            


Teaching

EOH 3210, Molecular Fundamentals

ARTSC 0130, First Experiences in Research


Selected Publications

1.      H.Y. Lin, P. Masso-Welch, Y.P. Di, J.W. Cai, J.W. Shen and J.R. Subjeck. The 170-kDa glucose-regulated stress protein is an endoplasmic reticulum protein that binds immunoglobulin. Molecular Biology of the cell, Vol. 4, p1109-1119, Nov. 1993. PMID:8305733

2.      Y.P. Di, E. Repasky, A. Laszlo, S. Calderwood, and J. Subjeck. HSP70 translocates into a cytoplasmic aggregate during activation. J of Cellular Physiology, 165:228-238, Nov. 1995. PMID:7593200

3.      Y.P. Di, E. Repasky, and J. Subjeck.  Fever-range, long duration hyperthermia, heat shock proteins, and the immune response.  Proceedings of the Tenth International Congress of Radiation Research, Eds. U. Hagen, U. Harder, H. Jung. and C. Streffer, p966-968, 1996.

4.      P.M.S. Reddy, G. An, Y.P. Di, Y.H. Zhao, and R. Wu. A palindromic primer-based mRNA differential display method to isolate vitamin A-responsive genes in airway epithelium: Characterization of nucleolin gene expression.  Am. J. of Respiratory Cell and Molecular Biology, 15:398-403, Sep. 1996. PMID:8810645

5.      Y.P. Di, E. Repasky, and J. Subjeck.  Distribution of HSP70, protein kinase C, and spectrin is altered in lymphocytes during a fever-like hyperthermia exposure. J of Cellular Physiology, 172:44-54, July 1997. PMID:9207924

6.      C.M. Soref*, Y.P. Di*, L. Hayden, Y.H. Zhao, M.A. Satre, and R. Wu. Characterization of a novel airway epithelial cell-specific short chain alcohol dehydrogenase/reductase gene whose expression is up-regulated by retinoids and is involved in the metabolism of retinol. J Biol Chem, 276(26):24194-202, June 29, 2001. (*Equal Contribution)  PMID:11304534

7.      Y. Chen, Y.H. Zhao, Y.P. Di, and R. Wu. Characterization of Human Mucin 5B Gene Expression in Airway Epithelium and the Genomic Clone of the Amino-Terminal and 5'-Flanking Region. Am. J. of Respiratory Cell and Molecular Biology, 25: 542-553, Nov. 2001. PMID:11713095

8.      W.H. Chang, S.P. Reddy, Y.P. Di, K. Yoneda, R. Harper, and R. Wu. Regulation of thioredoxin gene expression by Vitamin A in human airway epithelial cells. Am. J. of Respiratory Cell and Molecular Biology, 26: 627-635, May, 2002. PMID:11970916, DOI: 10.1165/ajrcmb.26.5.4276

9.      Y.P. Di, R. Harper, Y.H. Zhao, N. Pahlavan, and R. Wu. Molecular cloning and characterization of spurt, a human novel gene that is retinoic acid-inducible and encodes a secretory protein specific in upper respiratory tracts. J Biol Chem, 278(2):1165-1173, Jan. 10, 2003. PMID:12409287, DOI:10.1074/jbc.M210523200

10.   F. Gambelli, Y.P. Di, X Niu, M Friedman, T Hammond, DW Riches, and LA Ortiz.  Phosphorylation of tumor necrosis factor receptor 1 (p55) protects macrophages from silica-induced apoptosis. J Biol Chem, Jan., 2004. PMID:14570868

11.   W. Ning, C. Li, N. Kaminski, C. Feghali-Bostwick, S. Alber, Y.P. Di, S. Otterbein, R. Song, S. Hayashi, Z. Zhou, D. Pinsky, S. Watkins, J. Pilewski, D. Peters, J. Hogg, and A. Choi. Comprehensive gene expression profiles reveal novel pathways related to the pathogenesis of chronic obstructive pulmonary disease. Proceedings of the National Academy of Sciences of the United States of America, Proc Natl Acad Sci U S A, 101(41):14895-900, Oct 12, 2004. PMID:15469929, PMCID: 522001

12.   R. Harper, C.  Xu, Y.P. Di, Y. Chen, M. Privalsky, and R. Wu. Identification of a Novel MAGE D2 Antisense RNA Transcript in Human Tissues. Biochem Biophys Res Commun, 324<st1:citation w:st="on">(1):199-204, Nov 5, 2004. PMID:15465002,

13.   V.E. Kagan, V.A. Tyurin, J. Jiang, Tyurina Y, V. Ritov, A. Amoscato, A. Osipov, N. Belikova, A. Kapralov, V. Kini, I. Vlasova, Q. Zhao, M. Zou, Y.P. Di, D. Svistunenko, I. Kurnikov and G. Borisenko. Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors. Nature Chemical Biology 1, 223-232, 2005. PMID:16408039

14.   J. Zhao, R. Harper, A. Barchowsky and Y.P. Di. Identification of multiple MAPK-mediated transcription factors regulated by tobacco smoke in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2007 293:L480-L490, Aug 2007. PMID:17496060, PMCID:3431669

15.   S. Reynolds, A. Zemke, A. Giangreco, B. Brockway, R. Teisanu, J. Drake, T. Mariani, M. Taketo, Y.P. Di., and B. R. Stripp. Conditional stabilization of β-catenin expands the pool of lung stem cells. Stem Cells, 26(5):1337-46. May 2008. PMID:18356571

16.   D. Volonte, B. Kahkonen, S. Shapiro S, Y.P. Di, and F. Galbiati. Caveolin-1 expression is required for the development of pulmonary emphysema through activation of the ATM-p53-p21 pathway. J Biol Chem, 284(9): 5462-5466, Feb. 27 2009. PMID:19103597

17.   H. S. Deshmukh, A. McLachlan, J. J. Atkinson, W. D. Hardie, T. R. Korfhagen, M. Dietsch, Y. Liu, Y. P. Di, S. C. Wesselkamper, M. T. Borchers, and G. D Leikauf.  Matrix metalloproteinase (MMP) 14 mediates a phenotypic shift in the airways to increase mucin production. American Journal of Respiratory and Critical Care Medicine 180(9):834-45; Nov 1, 2009. PMID:19661247

18.   A. S. Jang, V. J. Concel, K. Bein, K. A. Brant, S. Liu, H. Pope-Varsalona, Dopico Jr RA, Y.P. Di., Knoell DL, Barchowsky A, G. D. Leikauf.  Endothelial Dysfunction and Claudin 5 Regulation during Acrolein-induced Lung Injury. Am. J. of Respiratory Cell and Molecular Biology, Vol 44. pp 483–490, Jun 4, 2010. PMID:20525806

19.   G. D. Leikauf, H. Pope-Varsalona, V. J. Concel, P. Liu, K. Bein, K. A. Brant, R.A. Dopico, Y.P. Di, A. S. Jang, M. Dietsch, M. Medvedovic, Q. Li, L. J. Vuga, N. Kaminski, M. You, D.R. Prows. Functional genomics of chlorine-induced acute lung injury in mice.  Proc Am Thorac Soc.;7(4):294-6, Jul., 2010. PMID:20601635

20.   P.L. Wright, J. Yu, Y.P. Di., R.J. Homer, G. Chupp, J.A. Elias, L. Cohn, W.C. Sessa. Epithelial reticulon-4B (Nogo-B) is an endogenous regulator of asthmatic inflammation. Journal of Experimental Medicine, 207(12):2595-607. Epub 2010 Oct 25., Nov 22, 2010. PMID:20975041

21.   F. Gally, Y.P. Di, S. K. Smith, M. N. Minor, Y. Liu, D. L Bratton, S. C. Frasch, N. M. Michels, S. R. Case and H.W. Chu. SPLUNC1 promotes lung innate defense against Mycoplasma pneumoniae infection in mice. American Journal of Pathology, 178(5):2159-67. May, 2011. PMID:21514430

22.   G. D. Leikauf, V. J. Concel,  P. Liu,  A. Berndt, A. S. Jang, K. Bein, K. A. Brant, M. Dietsch, H. Pope-Varsalona, R. A. Dopico, Jr., Y.P. Di, Q. Li,  L. J. Vuga, M. Medvedovic, N. Kaminski, M. You, D. Prows. Haplotype association mapping of survival during acute lung injury in mice implicates transforming growth factor beta signaling. Am J Respir Crit Care Med, 183(11):1499-509. Jun 1, 2011, Epub 2011 Feb 4, PMID:21297076

23.   L. Lukinskiene, S. Reynolds, C. Steele, B. Stripp, G.Leikauf, J. Kolls, and Y.P. Di.  Antimicrobial activity of PLUNC protects against Pseudomonas aeruginosa infection. J of Immunology, 187(1):382-90. Jul 1, 2011, Epub 2011 Jun 1. PMID:21632717

24.   N Vo, D Wang, G Sowa, W Witt, K Ngo, P Coelho, R Bedison, B Byer, R Studer, J Lee, Y.P. Di, and J Kang. Differential effects of nicotine and tobacco smoke condensate on human annulus fibrosus cell metabolism. J Orthop Res. 2011 Mar 29. doi: 10.1002/jor.21417. [Epub ahead of print] PMID:21448984

25.   Y.P. Di. Functional roles of SPLUNC1 in innate immune response against gram-negative bacteria. Biochem. Soc. Trans, 2011 Aug 1;39(4):1051-5 PMID:21787346

26.   P. Keohavong, B. Kahkonon, E. Kinchington, J. Yin, X. Liu, J. Jin, J. M. Siegfried and Y.P. Di. K-ras mutations in lung tumors from NNK-treated mice with lipopolysaccharide-elicited lung inflammation. Anticancer research, 2011 Sep;31(9):2877-82) PMID:21868532

27.   T. Richards,  C. Park, Y. Chen, K. F. Gibson, Y. P. Di, A. Pardo, S. Watkins5,  M. Selman, J. Pilewski, F. Sciurba, N. Kaminski, Y. Zhang. Allele Specific Transactivation of Matrix Metalloproteinase 7 by FoxA2 and Correlation with Plasma Levels in Idiopathic Pulmonary Fibrosis. Am J Physiol Lung Cell Mol Physiol. 2012 Apr; 302(8):L746-54. Epub 2012 Jan 20. PMID: 22268124.

28.   S. Tao, L. Zhu, P. Lee, W. Lee, , K. Knox, J. Chen, Y. P. Di and Yin Chen. Negative control of TLR3 signaling by TICAM1 downregulation. Am. J. of Respiratory Cell and Molecular Biology, 2012 May; 46(5):660-7. Epub 2011 Dec 28. PMID: 22205631.

29.   GD Leikauf, H Pope-Varsalona, VJ Concel, P Liu, K Bein, A Berndt, TM Martin, K Ganguly, AS Jang, KA Brant, RA Dopico Jr, S Upadhyay, Y. P. Di, Q Li, Z Hu, LJ Vuga, M Medvedovic, N Kaminski, M You, DC Alexander, JE McDunn, DR Prows, DL Knoell, JP Fabisiak. Am J Respir Cell Mol Biol. 2012 Mar 23. [Epub ahead of print] PMID: 22447970

30.   JV Thaikoottathil, RJ Martin, Y. P. Di, M Minor, S Case, B Zhang, G Zhang, H Huang, HW Chu. SPLUNC1 Deficiency Enhances Airway Eosinophilic Inflammation in Mice. Am J Respir Cell Mol Biol. 2012 Apr 12. [Epub ahead of print] PMID: 22499853

31.   R. Birru, B, Kahkonon, and Y. P. Di. Chronic Inflammation in the Pathogenesis of COPD and Lung Cancer. Proc Am Thorac Soc. 2012 May; 9(2):81. PMID: 22550252

32.   Y. P. Di, J. Zhao, and R. Harper. Cigarette smoke induces MUC5AC expression through the activation of Sp1. J Biol Chem, 2012 Aug 10;287(33):27948-58. Epub 2012 Jun 14. PMID: 22700966

33.   Y. Liu and Y. P. Di. Effects of second hand smoke on airway secretion and mucociliary clearance. Front. Physio. 3:342. doi: 10.3389/fphys.2012.00342, PMID: 22973232

34.   R. Birru, and Y. P. Di. Pathogenic mechanism of lung diseases associated with cigarette smoke induced inflammation. Front. Physio. 3:348. doi: 10.3389/fphys.2012.00348, PMID: 22973236

35.   S. Sayeed, L. Nistico, C. St Croix, and Y. P. Di. Multifunctional role of human SPLUNC1 in Pseudomonas aeruginosa infection. Infect Immun. 2013 Jan; 81(1):285-91. doi: 10.1128/IAI.00500-12. Epub 2012 Nov 6.PMID: 23132494

36.   Y. Liu, J. A. Bartlett, M. E. Di, J. M. Bomberger, Y. R. Chan, L. Gakhar, R. K. Mallampalli, P. B. McCray, Jr., and Y. P. Di. SPLUNC1/BPIFA1 contributes to pulmonary host defense against Klebsiella pneumoniae respiratory infection. Am J of Pathology 2013 May;182(5):1519-31. doi: 10.1016/j.ajpath.2013.01.050..PMID: 23499554

37.   Leikauf GD, Concel VJ, Bein K, Liu P, Berndt A, Martin TM, Ganguly K, Jang AS, Brant KA, Dopico Jr RA, Upadhyay S, Cario CL, Y. P. Di, Vuga LJ, Kostem E, Eskin E, You M, Kaminski N, Prows DR, Knoell DL, Fabisiak JP. Functional Genomic Assessment of Phosgene-induced Acute Lung Injury in Mice. Am J Respir Cell Mol Biol. 2013 Apr 5. [Epub ahead of print] PMID: 23590305

38.   Volonte D, Liu Z, Musille PM, Stoppani E, Wakabayashi N, Y. P. Di, Lisanti MP, Kensler TW, Galbiati F. Inhibition of nuclear factor-erythroid 2-related factor (Nrf2) by caveolin-1 promotes stress-induced premature senescence. Mol Biol Cell. 2013 Jun;24(12):1852-62. doi: 10.1091/mbc.E12-09-0666. Epub 2013 May 1. PMID: 23637463

39.   Y. P. Di, A. V. Tkach, N. Yanamala, S. Stanley, S Gao, M. R. Shurin, E. R Kisin, V. E. Kagan, A. Shvedova. Dual Acute Pro-Inflammatory and Anti-Fibrotic Pulmonary Effects of SPLUNC1 After Exposure to Carbon Nanotubes. Am J Respir Cell Mol Biol. 2013 May 30. [Epub ahead of print] PMID: 23721177

40.   Y. Liu, M. E. Di, H.W. Chu, X. Liu, L. Wang, S. Wenzel, and Y. P. Di. Increased susceptibility to pulmonary Pseudomonas infection in Splunc1 knockout mice. J of Immunology 2013 Oct 15;191(8):4259-4268. Epub 2013 Sep 18.PMID: 24048904

41.   Y.P. Di. Assessment of pathological and physiological changes in mouse lung through bronchoalveolar lavage. Methods Mol Biol. 2014;1105:33-42. doi: 10.1007/978-1-62703-739-6_3. PMID: 24623217

42.   Y. Zhang, R Birru, and Y.P. Di. Analysis of clinical and biological samples using microsphere based multiplexing Luminex system. Methods Mol Biol. 2014;1105:43-57. doi: 10.1007/978-1-62703-739-6_4. PMID: 24623218

YuanPu Peter Di
© 2017 by University of Pittsburgh Graduate School of Public Health

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