Coming soon

We have two publications that will be coming out soon. The last of Maddy’s work from her thesis will be published on July 14th! And the latest paper from Cindy is officially accepted with publication date TBD but likely in the next 4-6 weeks. More info and links to come!

ASV Wrap-Up

Zach, Kaleigh, and Rachael had a great time at ASV2023. See photos here.

I am going to try to update this blog more often. I’m not on twitter as much as I used to be...so look for more updates here!

ASV2023 - where can you find us?

We will be at ASV2023 at UGA in Athens, GA:

 

The crew is on their way!

 

SUNDAY 1:30 PM–1:45 PM W18-1 R. Rush, S. Ganaie, C. McMillen, D. A. Price, M. M. Schwarz, X. Cui, D. W. Leung, G. Amarasinghe, A. Hartman. Rift Valley fever virus displays high permissivity for trophoblast cells lines and requires Lrp1 for efficient infection

TUESDAY W59-7 3:30 PM–3:45 PM K. A. Connors, N. S. Chapman, C. McMillen, Z. D. Frey, R. M. Hoehl, J. McGaughey, M. Midgett, C. Williams, D. S. Reed, J. Crowe, A. Hartman. Therapeutic delivery of potent neutralizing human monoclonal antibodies improves survival after aerosol exposure to rift valley fever virus

TUESDAY P39-9 Z. D. Frey, K. A. Connors, S. Ganaie, D. A. Price, M. M. Schwarz, X. Cui, Z. P. Wills, D. W. Leung, G. Amarasinghe, A. Hartman. Characterizing Jamestown Canyon virus infection of primary neurons and dependence on Lrp1

Accepted & in press

The last paper from Maddy’s graduate work has been accepted at Science Advances. Publication date forthcoming ~2 weeks or so.

Sneak peek title: Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice

Congrats Bayley!

Bayley is an MPH student in IDM. She wrote her essay on research she did with our group on genetic polymorphisms in LRP1. Congrats Bayley on a successful presentation of your essay yesterday! Bayley will graduate at the end of this month.

Welcome to Austin!

I am very excited to bring on new students and their diverse perspectives on our work. Austin Hertel is the second PhD student from PMI that just joined us. Austin rotated in the fall and worked with Cindy on placenta related projects. He also did not seem to be scared away!

I notice a trend though. Rachael likes to take our rotation students into the RBL!

Austin will be working with Cindy on everything pregnancy and placenta.

Austin tell us:

“I am originally from Rochester, NY and attended Gannon University in Erie, PA. While at Gannon, I completed a bachelor’s degree in biology & public health and competed as a 5-year starter on the men’s wrestling team. Now in Pittsburgh, I live in Highland Park with my little black cat, Wednesday. Outside of the lab I like to keep as active as possible. During the winter, I am still involved in the sport of wrestling by volunteering at a local high school. In the summers, I enjoy mountain biking, hiking, and playing really bad golf! Besides physical activity I love to play music. I’ve played the guitar since high school and still occasionally enjoy a jam-session with friends. Fun fact, I also used to play the French horn and is still my favorite instrument.”

Welcome to Cade!

We are still recovering from Maddy’s defense and coming to the realization that she is no longer in the lab! We can’t ask her any more questions! Or where anything is!

Yet new fun changes are also here. We have TWO new PhD students that just started with us. I’ll be introducing each here. First up:….Cade Sterling!

Cade says: “I grew up in Chattanooga, TN near the tail end of the Appalachian range. I did my undergrad at the University of the South in Sewanee, TN, where I worked with Dr. Clint Smith on coronavirus reverse genetics and viral replication. Outside of the lab, I’m probably going on adventures with my wife or chasing the perfect cup of coffee — trying new roasters, coffees with experimental processing techniques, or changing my brew method."

Cade rotated with us in the fall and wasn’t scared off! Here he is with Rachael, getting a taste of the BSL3. We manage to have fun while we’re doing science!

Cade will be working on Lrp1 related projects. So excited to have fresh new ideas and perspectives!

Introducing Dr. Madeline Schwarz

Maddy successfully defended her thesis on Monday! Hartman Lab’s first PhD graduate!

Here is my introduction to Maddy:

Maddy received her undergraduate degree from THE Ohio State University with a BS in Agriculture and an Animal Sciences major. While at OSU, she worked as a surgical assistant in their lab animal resources group and also was a summer intern at Envigo. After graduating, Maddy worked for a year as a fellow at the Plum Island Animal Disease Center where she worked on Foot and mouth disease virus (FMDV).

This is when Maddy first contacted me by phone with interest in working in my lab. I encouraged her to apply to the IDM PhD program (she was originally considering the MS program). She did her first lab rotation with me in the fall of 2019 and then committed to my lab in March of 2020, right at the beginning of the COVID pandemic. So Maddy completed all of her thesis work under challenging pandemic conditions. In the first few months of her tenure in the lab, she worked as part of a larger CVR team on the monkey model of SARS-CoV-2 that we developed (Hartman PLOS Path 2020). She also worked with Devin, a former student and tech, on the olfactory paper (Boyles JGV 2020).

During this time, Maddy expressed an interest in developing an ocular disease model of Rift Valley fever. Eye disease is a frequent outcome in people infected with RVFV, yet no experimental studies existed in the literature - just some animal studies documenting the presence of virus in the eye. So she set about to develop a rat model to understand the disease process and pathology as a result of infection. She sought out advice from the Opthalmology department and designed a fundus imaging setup for use in BSL-3. While this was not her main project in the lab, she published a nice study in Journal of Virology (Schwarz JVI 2022).

Concurrently, we had been working with Gaya Amarasinghe’s lab at WashU on a project identifying a potential new receptor for RVFV. In the early days of this work, we were still trying to validate the screen results and determine their significance. Maddy’s experience with rodents from OSU was very valuable as she worked with Cindy and Joe on the early experimental testing in mice. By performing the crucial in vitro and in vivo studies with RVFV ZH501 strain, she was co-second author on our initial publication (Ganaie, Schwarz et al. Cell 2021).

From there, she ran with it - initially subjecting a panel of bunyaviruses to our in vitro Lrp1 assays and honing in on a strong phenotype with Oropouche virus (OROV), kindly provided to us by Natasha Tilston-Lunel and Paul Duprex. This results in a paper coming together rather quickly (Schwarz et al. PNAS 2022). The final part of her thesis involved heavy animal work, looking at the in vivo relevance of Lrp1 using tissue-specific Lrp1 KO mice. This work is currently under review, so stay tuned. In total, Maddy has been part of 7 publications out of my lab, with another under review.

Some of Maddy’s accolades include being awarded the William T. Green Award in Public Health for 2020. She gave a virtual talk at ASV2021, and attended the Negative Strand Virus (NSV) conference in Portugal this past June of 2022, where she won a poster prize in the pathogenesis category. She also won 1st place in the PhD category at our departmental research day this year.

Maddy and I knew she was a great fit for my lab right from the beginning. She works hard and is super focused. She never shied away from any potential experiment. I thank her for taking a chance on me and my research program. We will miss her tremendously! She has taken a job at Abound Bio, so she will be close by.

Here are some photos from Maddy’s defense and celebration after. Congratulations Dr. Schwarz!!! We are so proud of you!!!

The Dr. Madeline Schwarz Commemorative Plant now adorns my office:

 
 

Oropouche & Lrp1!

Our paper showing that the South American bunyavirus Oropouche uses Lrp1 for efficient cellular infection is now out in PNAS! This study was led by Maddy Schwarz and is part of our larger collaboration with WashU in St. Louis. Its very intriguing that Oropouche virus (Peribunyaviridae) and Rift Valley fever virus (Phenuiviridae) both use Lrp1 when they are distantly related and have virtually no homology in Gn. This suggest a shared structural motif for reliance on Lrp1. Lots more to come on this subject.

Figure 6 shows that co-infection of mice with OROV and the high-affinity Lrp1 binding protein mRAP can protect mice from lethal disease, illustrating the in vivo relevance of this interaction. The mutant mRAP protein can partially protect mice from OROV, whereas it was not able to protect mice at all from similar Rift Valley fever virus infection.

mRAPD3 protects mice from lethal OROV IC infection and significantly reduces infectious virus in the brain at 3 dpi. (A) Mice were infected with 100 PFU of OROV IC alone or in combination with either mRAPD3, mutant mRAPD3, or the control protein VP30. They were monitored for 15 d to determine percentage of survival in each group. (B) A subset of mice from each group was euthanized at 3 dpi to collect brain tissue, which was processed by viral plaque assay. (C) Immunofluorescent microscopy of brain tissues (cerebral cortex) from mice euthanized at 3 dpi (20×). Scale bars, 250 μm. Statistical significance was determined using a Mantel-Cox test for survival and two-way ANOVA for log-transformed data. Experiments were repeated four times. **P < 0.01; ***P < 0.001; ****P < 0.0001. No tx, No treatment; mut, mutant.

Congrats to Maddy! This paper came together in a relatively short period of time!