Katarzyna Zwolinska
Louisiana State University Health Sciences Center-Shreveport, LA·Microbiology & Immunology
Human papillomaviruses (HPV) infect the skin and the moist linings of the body, and some types cause tumors such as cervical cancer. To cause disease, the virus must get its DNA into the nucleus of dividing cells at the base of these tissues, and then keep that DNA there as the cells divide again and again.
- Fields
Microbiology & Immunology
Biology
Genetics
- Topics
human papillomavirus
virus entry
intracellular trafficking
- Grants
- 2 known grants, through Mar 2029
What they work on
- Test whether the direction of microtubule-based transport of the HPV genome switches during cell division, and whether the motor proteins dynein and Kif11 drive it, using inhibitor and live-cell tracking experiments in infected keratinocytes.
- Test whether specific phospholipase C isoforms, enzymes that cleave membrane lipids, dissolve the vesicle that carries the viral genome into the nucleus, using knockdown and knockout cells with differential staining and electron microscopy.
- Determine whether recruitment of particular PML protein isoforms explains the delayed arrival of Sp100 at PML nuclear bodies forming around incoming HPV genomes, and whether this reorganization controls how actively the genome is transcribed.
- Identify the factors that limit tethering of HPV16 and HPV31 genomes to mitotic chromosomes, testing the hypothesis that copy number is maintained by restricted tethering rather than by control of replication initiation.
- Define the lysosomal, likely autophagy-based pathway that degrades viral genomes stranded in the cytoplasm, and pinpoint which functions of the viral E7 oncoprotein are required for this degradation.
- Determine how cytoplasmic HPV genomes avoid activating cGAS/STING, the cell's sensor for misplaced DNA, in keratinocytes that have an otherwise functional pathway.
More about the research
Both steps are poorly understood. Two linked projects follow the virus from the moment it enters a cell to the point where its genome settles in and is copied, using a cell culture system that infects primary human keratinocytes (the main cell type of skin and mucosal surfaces) efficiently while still allowing viral genes to be mutated and tested.
Why it matters
Persistent HPV infection underlies cervical and other epithelial cancers. By pinpointing the cellular machinery the virus depends on to deliver its DNA into the nucleus and to retain genome copies in dividing cells, the work could reveal targets for blocking infection before it is established or for clearing existing infections. The finding that viral DNA in the cytoplasm escapes the cell's DNA alarm system may also explain how these infections avoid immune detection.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Michelle A Ozbun
University of New Mexico, NM·Microbiology & Immunology
Determine how MEK inhibition changes the built-in antiviral responses of keratinocytes in MmuPV1-infected mouse tumors and HPV-infected raft cultures, using single-cell and spatial transcriptomics.
Pippa Cosper
University of Wisconsin-Madison, WI·Medicine & Clinical Research·Early-career
Define the types and extent of chromosomal instability, ongoing errors in how dividing cells sort chromosomes, caused by different HPV genotypes and different levels of the viral oncogenes that drive cancer.
James Robertson
Middle Tennessee State University, TN·Neuroscience
Create new transgenic Drosophila lines that tag the flies' own neuropeptides with fluorescent markers such as mScarlett3, using tissue-specific CRISPR, to confirm that neuropeptides are sorted into dense core vesicles at the mRNA level.
The school
Louisiana State University Health Sciences Center-Shreveport: 6 labs on PI Pages, $32M a year on research, 9 research doctorates a year.
More about Louisiana State University Health Sciences Center-Shreveport
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