Yvonne M. W. Janssen-Heininger
University of Vermont, VT·Biochemistry
Inside cells, chemical oxidation does more than cause damage. It also acts as a signal that switches proteins on and off.
- Fields
Biochemistry
Medicine & Clinical Research
Pharmacology
- Topics
idiopathic pulmonary fibrosis
lung adenocarcinoma
lung cancer
- Grants
- 3 known grants, through Apr 2030
What they work on
- Determine whether the enzyme GSTP drives glutathionylation of OTUB1 and keeps KRT8-high transitional lung cells from maturing into AT1 cells, using a clinically tested GSTP inhibitor and IPF patient organoids.
- Test whether glutathionylation of OTUB1 at cysteine 23 blocks NEDD4L-mediated tagging of MTOR, prolonging MTOR activity and stalling air-sac repair, using the OTUB1-binding compound EN523 and patient lung slices.
- Determine whether loss of glutaredoxin (GLRX) speeds lung tumor formation driven by mutant KrasG12D in mice, and whether OTUB1 glutathionylation stabilizes the System XC- transporter to raise glutathione in tumors.
- Test whether delivering GLRX with an AAV viral vector lowers tumor glutathione and boosts cisplatin killing in patient-derived lung adenocarcinoma organoids and KrasG12D mouse tumors.
- Determine whether ER oxidative folding by protein disulfide isomerase A3 and impaired collagen autophagy cause fibroblasts to secrete glutathionylated collagen 1A1 that activates myofibroblasts in aged lungs.
- Test whether GLRX, including a new oxidation-resistant form, reduces collagen glutathionylation, myofibroblast activation and age-associated lung fibrosis in knockout mice and IPF patient fibroblasts.
More about the research
One such change, called S-glutathionylation, attaches the small antioxidant molecule glutathione (GSH) to reactive cysteine building blocks in proteins. The enzyme glutaredoxin (GLRX) removes it again. These grants ask how disrupting this on/off system drives two lung diseases. One is idiopathic pulmonary fibrosis (IPF), a fatal lung scarring disease. The other is lung adenocarcinoma (LUAD), the most common type of lung cancer. A shared player is OTUB1, a protein that controls whether other proteins are tagged for destruction. The projects also test GLRX and related compounds as possible treatments.
Why it matters
Idiopathic pulmonary fibrosis usually kills within 3–5 years of diagnosis and has few effective treatments. Lung adenocarcinoma is the most common lung cancer. This work could point to new ways to restore lung repair in IPF and reverse persistent scarring in aging lungs. It tests a GSTP inhibitor already used in clinical trials and purified forms of glutaredoxin. In lung cancer, raising GLRX levels could make standard cisplatin chemotherapy more effective.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Beiyun Zhou
University of Southern California, CA·Physiology
Identify how loss of the endoplasmic reticulum chaperone GRP78 disturbs mitochondrial energy production and biosynthesis in alveolar epithelial cells, and how this promotes pulmonary fibrosis, using AT2 cell-specific Grp78 knockout mice.
Yong Huang
University of Virginia, VA·Medicine & Clinical Research
Test whether reducing lung stretch by paralyzing one side of the diaphragm slows fibrosis progression in the outer and lower lung of mice with bleomycin-induced lung injury.
Timothy Blackwell
University of Michigan, MI·Medicine & Clinical Research
Detect gene activity biomarkers of pre-clinical disease in asymptomatic relatives of familial pulmonary fibrosis patients, using single-cell RNA sequencing of blood immune cells such as CD14+ monocytes alongside high-resolution CT findings.
The school
University of Vermont: 16 labs on PI Pages, $246M a year on research, 76 research doctorates a year.
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