Jiashu Xie
University of Minnesota, MN·Pharmacology
Chemotherapy often stops working because tumor cells learn to pump the drugs back out. Pumps in the cell membrane called ATP-binding cassette (ABC) transporters push a wide range of chemically unrelated drugs out of the cell, producing multidrug resistance and contributing to relapse and treatment failure.
- Fields
Pharmacology
Chemistry
Medicine & Clinical Research
- Topics
multidrug resistance
ABC transporters
drug efflux
- Grants
- 1 known grant, through Aug 2027
What they work on
- Screen an in-house library of about 30 deazaflavin analogs for inhibition of the MRP1 drug efflux pump using membrane vesicle transport assays and a cell-based calcein retention assay, and define potency and structure-activity relationships.
- Establish selectivity of the lead analogs for MRP1 over other major ABC transporters including P-gp, BCRP, MRP2 and MRP3, to limit interference with normal drug handling.
- Identify the MRP1 amino acid residues critical for inhibition by the deazaflavin analogs using site-directed mutagenesis of the transporter.
- Test whether advanced analogs resensitize lung cancer and neuroblastoma cell lines to chemotherapy, correlating the effect with MRP1 protein expression and inhibition.
- Profile in vivo toxicity of top analogs in mice and evaluate anti-tumor activity in combination with the TOP2 poison etoposide in a xenograft model of multidrug-resistant lung cancer.
More about the research
One way around this is a small molecule that blocks the pump, letting standard chemotherapy build up inside the cancer cell again — the strategy pursued in this project.
Why it matters
Drug efflux is a major reason chemotherapy fails in cancers such as small cell lung cancer and neuroblastoma. A selective MRP1 blocker that restores sensitivity to existing drugs like etoposide, without increasing their delivery to healthy tissue, could allow effective treatment at tolerable doses. The project aims to define the mechanism and sensitizing potential of these compounds as a foundation for later preclinical development.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Keykavous Parang
Chapman University, CA·Pharmacology
Compare how five peptide-doxorubicin conjugates (PDCs) differ in killing cancer cells versus heart muscle cells, measuring reactive oxygen species, cell death (apoptosis) and calcium release.
W Todd Lowther
Wake Forest University, NC·Biochemistry
Design and synthesize new compounds based on screening hits to explore the structure–activity relationships of hydroxyproline dehydrogenase (HYPDH) inhibitor scaffolds, improving potency, selectivity and drug-like properties.
Jing An
University of California-San Diego, CA·Pharmacology
Develop CXCR4-targeted stem cell mobilizers, molecules that draw stem cells toward a site, with optimized pharmacological and biological properties, building on small molecule-peptide conjugate agonists with higher receptor affinity and lower synthetic cost.
The school
University of Minnesota: 88 labs on PI Pages, $1.4B a year on research, 722 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.