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Bethany Rhein defends PhD thesis

Friday, October 23, 2015

Bethany Rhein successfully defended her PhD thesis, "The role of TIM-4 in Ebola virus infection," on Friday, October 23, 2015. Beth is pictured here with her mentor, Dr. Wendy Maury.

Ebola virus (EBOV) is a member of the Filoviridae family of highly pathogenic viruses that cause severe hemorrhagic fever and is the causative agent of the 2014 West Africa outbreak. Currently, there are no approved filovirus treatments to combat these sporadic and deadly epidemics. One target for EBOV antiviral therapy is to block viral entry into host cells.

Recently, phosphatidylserine (PtdSer) receptors that are responsible for the clearance of dying cells have been appreciated to mediate entry of enveloped viruses including filoviruses. The human and mouse T- cell Immunoglobulin Mucin Domain 1 (hTIM-1 and mTIM-1) and family members hTIM-4 and mTIM-4 serve as filovirus receptors, significantly enhancing EBOV entry. TIM-dependent virus uptake occurs via apoptotic mimicry by binding to PtdSer on the surface of virions through a conserved PtdSer binding pocket within the amino terminal IgV domain. TIM-4 is expressed on antigen presenting cells, including dendritic cells and macrophages, which are critical in early EBOV infection.

My studies have defined the molecular details of virion/TIM-4 interactions and establish the importance of TIM-4 for EBOV infection of murine peritoneal macrophages. In addition, all previous work by others established the role of the TIM proteins in EBOV entry through in vitro studies. My studies are the first to demonstrate the importance of TIM-1 and TIM-4 expression for in vivo viral pathogenesis in mice. These studies suggest that the TIM proteins may serve as relevant targets for future filovirus therapeutics.

ABOUT BETH

Beth was born and raised in Coon Rapids, MN, just north of Minneapolis/St Paul. Growing up with her younger brother Matt, she was raised by two wonderful parents, Kay and Keith. She always enjoyed learning and even from a young age was interested in teaching as she spent countless hours helping family friend Karen in her 1st grade classroom. During freshman year of high school, she was encouraged to pursue her love of science and discovery through science fair. Her parents were not thrilled that this endeavor meant storage of her test subjects (numerous buckets of earthworms) in the basement all winter. However, her dedication and hard work resulted in a trip to the MN State Science Fair.

Her excitement for scientific process led her to the University of St. Thomas in St. Paul, MN, where she pursued an undergraduate degree in Biology. By the end of her first undergraduate semester in the fall of 2006, she was working as a lab assistant and began her own research project in the Microbiology lab of Dr. Jayna Ditty. She investigated the impact of light:dark cycles on regulation of cellular activities of Cyanobacteria. This project opened her eyes to the amazing world and power of microorganisms.

Beth came to The University of Iowa in August of 2010 and fell in love with viruses from her first rotation in Wendy Maury’s lab, which she subsequently joined in 2011. She has studied the role of TIM proteins in Ebola virus entry and viral pathogenesis along with investigating the ability of interferon-gamma to serve as a novel Ebola virus therapeutic. She has had the privilege of presenting her work at several conferences including several annual American Society for Virology meetings, the 2nd International meeting of clearance of dying cells in Rhodes, Greece, and the 7th International symposium on Filoviruses in Washington, DC. After finishing her work at The University of Iowa, Beth hopes to continue to follow her passion for understanding viral pathogenesis for development of novel therapeutics.

Outside of lab, you will find Beth at the gym lifting heavy weights (as Rachel would say “bench pressing cars”), hiking mountains, and biking with her boyfriend Jeff. She loves to cook and bake and is always experimenting with new recipes. She also enjoys spending time with friends and family along with traveling to new places.