Department of Medicine

University of Pittsburgh

Division of Pulmonary, Allergy, and Critical Care Medicine
3459 Fifth Avenue,
628 NW
Pittsburgh, PA 15213
Academic Office: (412) 692-2210
Comprehensive Lung Center (Patient Care and Referral): (412) 648-6161

Yingze Zhang, PhD

Associate Professor
UPMC Montefiore Hospital - NW628
3459 Fifth Avenue
Pittsburgh, PA 15213

Phone: 412-624-7225
Fax: 412-624-1670
Email: zhangy@upmc.edu
Assistant: Terri Heinrich
Assistant Email: heinrichta@upmc.edu

Bio

Yingze Zhang received her PhD from the University of Pittsburgh School of Medicine in 1997 and her post-doctoral training in Human Genetics and Rheumatology & Cellular Immunology at the Allegheny University of Health Systems and University of Pittsburgh School of Medicine, respectively. She joined the faculty at the Center for Craniofacial and Dental Genetics of the University of Pittsburgh School of Dental Medicine in 1999 and moved to her current position at the Division of Pulmonary, Allergy and Critical Care Medicine in 2002. Prior to her doctoral training, she obtained a MS degree in Biochemistry from Duquesne University and another MS degree in Infectious Disease and Microbiology from the University of Pittsburgh Graduate School of Public Health. Her earlier research was  on the gene regulation of HSV-1 and molecular diagnosis of infectious diseases. During her doctoral and post-doctoral training, Dr. Zhang conducted researches on the genetics and molecular basis of several genetic disorders, including Crouzon syndrome, hereditary pancreatitis, Papillon Lefever syndrome, Haim Munk syndrome. hereditary gingival fibromatosis, and aggressive periodontitis.  Since 2002, she has been conducting genetic association study for candidate genes associated with idiopathic pulmonary fibrosis, interstitial lung diseases associated with connective tissue diseases, and acute lung injury. Her current research focuses on the molecular and genetic basis of pulmonary diseases and biomarker discovery. She is a coauthor of more than 40 peer-reviewed publications.

Academic and Research Interests

Dr. Zhang’s current research is focused on the molecular and genetic basis of pulmonary diseases including COPD, ILD, sleep apnea, and acute lung injury and biomarker discovery of these diseases. She is a co-investigator on two of the NIH SCCOR grants awarded to the University of Pittsburgh. Her laboratory is responsible for the sample processing/banking and peripheral biomarker analysis.
 
One of her genetic research project is to identify the genetic predisposition factors to ILD associated with connective tissue diseases. She established collaborations with Dr. Thomas Medsger, Jr.and Dr. Chester Oddis in 2002 and have banked more than 1000 DNA samples from patients with SSc and PM/DM. Recently, her group has obtained an internal grant for performing a pilot GWAS study using their SSc cohort. Once this  work finishes, she will fine mapped the identified candidate regions and analyze the molecular basis for any positively associated genetic polymorphisms in this cohort. Currently her lab is following up on the functional significance of several gene polymorphisms that have been shown to be associated with idiopathic pulmonary fibrosis.

In collaboration with Dr. Joseph Zmuda at the graduate school of public health, she has been conducting functional analysis of the genetic variants that have been shown to be associated with bone phenotypes. Their group has been focused on the genes involved in the Wnt pathway and just published their finding in JBMR on promoter polymorphisms in FZD gene. Using molecular techniques, they identified an Egr1-dependet allele specific regulation of the FZD gene that has been associated with bone phenotypes. The ultimate goal is to study these genes in a cohort of COPD since osteoporosis is more common in patients with COPD and further analysis the functional consequence of associated variants in lung and bone tissues of these patients.

She also directs the translational core lab for the Division of Pulmonary, Allergy and Critical Care Medicine. The translational core lab has banked clinical samples from patients with lung diseases and matched controls since 2002 and has been served as a vital resource for translational research within the division. The translational core lab has also provided laboratory assistance for investigators.

Functional analysis of the Egr-1 dependent/allele specific regulation of the FZD1

This figure illustrates the identification of Egr1 dependent, allele specific regulation of the FZD1 gene associated with rs2232158 polymorphism. a). Schematic of the FZD1 5’ UTR region and the creation of an Egr1 binding site associated with the rs2232158C allele. b) Western blot analysis of Egr1 protein in MG63 and SaOS-2 cells, the cell types for the in vitro study. c) Allelic specific binding to the rs2232158 specific probes with recombinant Egr 1 using EMSA. Increasing Egr1 specific complex (see arrowhead) was detected for the C allele with increasing Egr1 recombinant protein concentration. The Egr1 specific binding was abolished with Egr1 antibody treatment and super shift bands were observed (see arrows). d) Binding affinity for Egr1 to rs2232158 alleles. Transcription Factor ELISA (Panomics) and biotinylated probes designed for each allele of rs2232158 (G allele in black and C allele in white) were used. Differences in binding were tested using the Wilcoxon rank sum test (<0.05 indicated by *). e) Binding affinity for Egr1 to rs2232158 alleles at various concentrations of nuclear extract (G allele in black and C allele in grey). f) Activity of the rs2232158 specific FZD1 promoter. The promoter activity for different rs2232158 alleles were assessed by transfecting MG63 and SaOS-2 cell lines with luciferase reporter plasmids (G allele in black and C allele in white). Differences in activity were tested using the Wilcoxon rank sum test (<0.05 indicated by *)

Aberrant expression of the Caveolin-1 expression in IPF lung tissue. 

This picture illustrates the specific down regulation of Cav-1 expression in IPF lungs in comparison to normal lungs. The expression level of Cav-1 in IPF and normal lung tissues are shown (B) and demonstrate the down regulation in the IPF lung. To further determine whether this down regulation is cell type specific, we performed double immuno-staining using cytokeratin, an epithelial cell marker, and CD31, an endothelial cell marker. As shown in C, the Cav-1 expression is down regulated in cells positive for the cytokeratin. In contrast, expression of the Cav-1 is not affected in cells that are positive for the CD31. These results demonstrate the expression of Cav-1 gene is specifically down regulated in the epithelial cells but not endothelial cells of the IPF lung tissues.

Schematic description of The translational Lab sample collection, processing and archiving.
This flow diagram outlines the sample collection, processing and archiving of clinical samples for the Translational Core Lab. The archived samples provide a vital resource for proteomics, genomics, and biomarker discovery and validation research. 

Key Publications

Yerges LM, Zhang Y, Cauley JA, Kammerer CM, Nestlerode CS, Wheeler VW, Patrick AL, Bunker CH, Moffett SP, Ferrell RE, Zmuda JM. Functional Characterization of Genetic Variation in the Frizzled 1 (Fzd1) Promoter and Association with Bone Phenotypes: More to the Lrp5 Story? J Bone Miner Res. 2008 Aug 20. [Epub ahead of print]

 Wang XM, Zhang Y, Kim HP, Zhou Z, Feghali-Bostwick C, Liu F, Ifedigbo E, Xu X, Oury TD, Kaminski N, Choi AMK. Caveolin-1: A critical regulator of lung fibrosis in idiopathic pulmonary fibrosis. 2006. JEM 203(13):2895-906.

Zhang Y, Syed R, Uygar C, Pallos D, Gorry MC, Firatli E, Cortelli JR, VanDyke TE, Hart PS, Feingold E, Hart TC. Evaluation of human N-formylpeptide receptor (FPR1) SNPs in aggressive periodontitis patients. Genes Immun. 4:22-29, 2003

PubMed Link