A photo of Timothy Weaver.

Timothy E. Weaver, MS, PhD


  • Co-Director, Division of Pulmonary Biology
  • Professor, UC Department of Pediatrics

About

Biography

For many years, I have been interested in lung development and disease, especially research focused on defining the molecular machinery that maintains the integrity and role of the epithelial barrier in the lung.

The primary research my colleagues and I concentrate on is identifying the molecular pathways that connect mutations in the SFTPC gene (encoding surfactant protein C) to the occurrence of interstitial lung disease (ILD) among both adults and children.

My laboratory has achieved multiple notable discoveries. We have a long history for discovery dating back to our first finding that overexpression of a disease-associated SFTPC allele in terms of the endogenous WT allele gave rise to type II epithelial cell (AT2) injury/fatality in transgenic mice, which was associated with endoplasmic reticulum (ER) stress in both mouse and human AT2 models.

We subsequently identified ER chaperones that are part of the folding/maturation of the SP-C proprotein. We established that ERdj4 was a vital element of the quality control mechanisms needed for recognition and quick degradation of the mutant SP-C proprotein.

I was steered toward my research interests by personal reasons. Both my daughter and granddaughter were born prematurely, which led them to suffer from lung disease. These encounters formed my interest in genetic lung disease.

The National Institutes of Health (NIH) have continuously funded my research since 1986, which includes a MERIT (R37) award from the National Heart, Lung and Blood Institute from 2001 to 2011. In addition, I previously served as the director of the Molecular and Developmental Biology graduate program. Over the last 15 years, I trained 14 graduate students and 11 postdoctoral fellows. Eight of these students are now faculty members at institutions in the United States, Japan, France, the United Kingdom and Germany.

I have more than 30 years of experience in pulmonary biology and started working at the Cincinnati Children’s Hospital Medical Center in 1986. My research has been published in respected journals, such as Scientific Reports, The Journal of Biological Chemistry, The Journal of Cell Biology, Molecular Biology of the Cell and PLoS ONE.

Publications

Selected

The Phosphatidylcholine Transfer Protein Stard7 is Required for Mitochondrial and Epithelial Cell Homeostasis. Yang, L; Na, C; Luo, S; Wu, D; Hogan, S; Huang, T; Weaver, TE. Scientific Reports. 2017; 7.

Selected

Haploinsufficiency for Stard7 is associated with enhanced allergic responses in lung and skin. Yang, L; Lewkowich, I; Apsley, K; Fritz, JM; Wills-Karp, M; Weaver, TE. Journal of Immunology. 2015; 194:5635-5643.

Selected

Deficiency of the BiP cochaperone ERdj4 causes constitutive endoplasmic reticulum stress and metabolic defects. Fritz, JM; Dong, M; Apsley, KS; Martin, EP; Na, C; Sitaraman, S; Weaver, TE. Molecular Biology of the Cell. 2014; 25:431-440.

Selected

Comparative proteomic analysis of lung lamellar bodies and lysosome-related organelles. Ridsdale, R; Na, C; Xu, Y; Greis, KD; Weaver, T. PLoS ONE. 2011; 6.

Selected

ERdj4 and ERdj5 are required for endoplasmic reticulum-associated protein degradation of misfolded surfactant protein C. Dong, M; Bridges, JP; Apsley, K; Xu, Y; Weaver, TE. Molecular Biology of the Cell. 2008; 19:2620-2630.

Selected

Adaptation and increased susceptibility to infection associated with constitutive expression of misfolded SP-C. Bridges, JP; Xu, Y; Na, CL; Wong, HR; Weaver, TE. Journal of Cell Biology. 2006; 172:395-407.

Selected

Processing of pulmonary surfactant protein B by napsin and cathepsin H. Ueno, T; Linder, S; Na, CL; Rice, WR; Johansson, J; Weaver, TE. Journal of Biological Chemistry. 2004; 279:16178-16184.

Selected

Expression of a human surfactant protein C mutation associated with interstitial lung disease disrupts lung development in transgenic mice. Bridges, JP; Wert, SE; Nogee, LM; Weaver, TE. Journal of Biological Chemistry. 2003; 278:52739-52746.

Selected

SP-B deficiency causes respiratory failure in adult mice. Melton, KR; Nesslein, LL; Ikegami, M; Tichelaar, JW; Clark, JC; Whitsett, JA; Weaver, TE. American Journal of Physiology - Lung Cellular and Molecular Physiology. 2003; 285:L543-L549.

Selected

Secretion of surfactant protein C, an integral membrane protein, requires the N-terminal propeptide. Conkright, JJ; Bridges, JP; Na, CL; Voorhout, WF; Trapnell, B; Glasser, SW; Weaver, TE. Journal of Biological Chemistry. 2001; 276:14658-14664.