Jixin Dong
University of Nebraska Medical Center, NE·Pharmacology
Paclitaxel, sold as Taxol, is one of the most widely used chemotherapy drugs, given for ovarian, breast, lung and pancreatic cancer. It is an antitubulin agent: it jams the microtubule scaffolding that cells need to divide, stalling them in mitosis.
- Fields
Pharmacology
Biochemistry
Medicine & Clinical Research
- Topics
ovarian cancer
breast cancer
paclitaxel
- Grants
- 1 known grant, through Jul 2027
What they work on
- Establish in animal models whether protein kinase R, an enzyme best known in antiviral immunity, determines how tumors respond to antitubulin drugs such as paclitaxel.
- Work out how antitubulin drugs regulate this kinase, focusing on newly identified phosphorylation sites that appear during drug-induced mitotic arrest and normal mitosis.
- Trace the downstream signaling that sets paclitaxel sensitivity, testing whether the kinase acts by changing levels of Bcl2, a protein that prevents cell death.
- Test whether pairing paclitaxel with kinase activators characterized in the project, or with FDA-approved Bcl2 inhibitors, overcomes resistance in ovarian and breast cancer models.
More about the research
Yet responses vary enormously between patients and resistance is common, so there is a practical need both for markers that predict who will benefit and for ways to restore sensitivity. This project builds a case that one enzyme sets much of that response: protein kinase R, better known for its role in the innate immune reaction to viruses and in tumor formation.
Why it matters
Ovarian cancer that returns or stops responding to paclitaxel is difficult to treat. If this signaling axis drives sensitivity, pairing paclitaxel with kinase activators or with existing FDA-approved Bcl2 inhibitors could improve outcomes for those patients. Measuring the pathway's levels and activity in a tumor may also serve as a marker to predict response before treatment begins.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
XiangXi Mike Xu
University of Miami, FL·Medicine & Clinical Research
Determine how brief low intensity ultrasound affects the microtubule network of hair matrix keratinocytes and hair follicle epithelial stem cells exposed to paclitaxel, a drug that locks microtubules in place.
Zahid Siddik
University of Texas MD Anderson Cancer Center, TX·Pharmacology
Test whether reducing MDM4, a natural inhibitor of the p53 tumor suppressor, restores basal p53 phosphorylation in cisplatin-resistant rare ovarian cancer subtype models, both in cultured cells and in animals.
Eric Ubil
University of Kentucky, KY·Microbiology & Immunology
Determine how tumor cells regulate secretion of proteins that activate the macrophage Mer receptor, and test whether their levels in human tumors predict response to chemotherapy.
The school
University of Nebraska Medical Center: 20 labs on PI Pages, $657M a year on research, 82 research doctorates a year.
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