Ronald Harty
University of Pennsylvania, PA·Microbiology & Immunology
Ebola and Marburg viruses cause sudden outbreaks of hemorrhagic fever, and they can also linger in the body for months and re-emerge, leaving survivors with long-term illness or death. These viruses are small and depend heavily on borrowing machinery from the cells they infect.
- Fields
Microbiology & Immunology
Biology
Biochemistry
- Topics
Ebola virus
Marburg virus
filovirus
- Grants
- 2 known grants, through Aug 2027
What they work on
- Test whether the Ebola VP40 matrix protein, which lacks a nuclear address tag, enters the nucleus by riding along with YAP, the Hippo pathway's gene-switching protein, using wild-type versus mutant PPxY motifs that bind host WW domains.
- Determine what nuclear VP40 does by asking whether a VP40-YAP interaction shifts YAP-driven gene programs toward conditions favoring virus production and spread, in cells including liver cells, HUVEC endothelial cells and monocyte-derived macrophages.
- Test whether stiffness of the extracellular matrix, the protein scaffold around cells, determines Ebola and Marburg infectivity, using atomic force microscopy, polyacrylamide hydrogels of tunable stiffness and live filovirus infection assays.
- Determine whether five candidate matrix-associated proteins, some of them YAP target genes, modulate filovirus infection, using CRISPR/Cas9 knockout cells, pseudotyped virus transductions and RNA sequencing.
- Ask whether filovirus infection in turn remodels the host cell environment by changing where YAP sits, how active it is, and which matrix proteins the cell makes.
More about the research
That dependence is also a weakness: if we can map which host proteins the virus grabs, those contact points become candidate drug targets. Work in this lab centers on one viral protein, VP40, the matrix protein that shapes new virus particles and pushes them out of the cell, and on the host proteins it latches onto. Two projects follow that theme in different directions: one asks what VP40 does inside the cell nucleus, a place it was not expected to go, and the other asks how the mesh of proteins outside cells influences whether infection succeeds.
Why it matters
There are few treatments for Ebola and Marburg virus disease, and drugs aimed at host proteins the virus must borrow are harder for the virus to escape by mutation. Mapping how the viral VP40 protein reaches the nucleus, and how the stiffness and composition of the surrounding tissue scaffold change infectivity, could point to host-directed antiviral targets and to the possibility of making tissue environments less hospitable to these viruses.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jing Yang
University of California-San Diego, CA·Biochemistry
Determine how the Hippo pathway, through the LATS1/2 kinases, controls transcription of ESR1, the main estrogen receptor gene, in breast cells and what ESR1 contributes to Hippo biology in breast tissue.
Wenqi Wang
University of California-Irvine, CA·Biochemistry
Characterize the molecular architecture of the Hippo kinase cascade, the chain of phosphate-adding enzymes MST and LATS and their partners, and map the regulatory networks around it.
Yong-Hui Zheng
University of Illinois Chicago, IL·Microbiology & Immunology
Characterize how MARCH8, a membrane-anchored ubiquitin ligase, blocks maturation of the HIV-1 envelope protein gp160 during infection of primary human cells and human T cell lines, using RNA silencing and CRISPR/Cas9 knockout.
The school
University of Pennsylvania: 90 labs on PI Pages, $2.2B a year on research, 750 research doctorates a year.
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