When dozens of University of Wisconsin blood researchers escape to sunny San Diego this weekend, they will not just be there for the weather – they are attending the American Society for Hematology’s (ASH) Annual Conference.
The 60th annual conference, held December 1-4, features presentations from several UW Carbone Cancer Center and researchers – along with over 3000 presentations from the top blood researchers in the world. Talks and poster presentations will include research on blood stem cells as well as blood cancers and other diseases.
On Monday, graduate student Adhithi Rajagopalan will be giving a follow-up talk from the one she presented at a conference this past April. There, she announced that she and colleagues had developed the first mouse model for advanced multiple myeloma. A previous model only mimicked the early stages of the disease, when it tends to respond better to treatment. Rajagopalan is in the research group of Dr. Jing Zhang, a UW Carbone faculty member in the McArdle Laboratory for Cancer Research and co-director of the UW Blood Research Program.
“Mainly what’s new is that those myeloma cells from our mouse model, we can take them out and culture them in a petri dish in an incubator,” Rajagopalan says. “And this is cool because with cells from the previous model – what was the gold standard model for multiple myeloma – could not be cultured.”
Growing the myeloma cells outside of mice means the researchers can more quickly conduct experiments on them, such as testing drug treatments. Additionally, cells grown in a dish are much easier to manipulate genetically, meaning researchers can introduce mutations commonly found in multiple myeloma and see how different genes affect disease progression and treatment.
“And here’s where I’m going to defer in my talk to another presentation from our close collaborators,” Rajagopalan says of a poster being presented from the UW Carbone lab of Dr. Fotis Asimakopoulos. “His group altered the myeloma cells so that they can be infected by an avian viral vector, even in the animal. This is great because it really simplifies the way you can introduce specific genetic changes not just to cells in a dish but also in mice, several genes at a time.”
Also presenting Monday is Dr. Ruiqi Liao, a postdoctoral researcher with Dr. Emery Bresnick, director of the UW Blood Research Program and faculty leader for UW Carbone’s genetic and epigenetic mechanisms of cancer program. In Liao’s talk, he will present his research on the role of heme – a chemical produced by red blood cells most commonly known for its role in transporting oxygen through blood – in the formation of red blood cells from their blood stem cell precursors.
“We know that heme is an important metabolite in precursor cells, and that both heme and the protein GATA1 can turn on genes during cell development. So we compared RNA and protein expression in mouse erythroid precursor cells with and without GATA1 and with or without heme to identify targets of GATA1 and heme,” Liao says. “We focused on one GATA1- and heme-activated gene that encodes a zinc exporter protein, which transports zinc out of the cells when it’s expressed, and one GATA1-induced zinc importer gene.”
Liao and colleagues measured zinc levels in precursor cells, finding that zinc levels rise in early development when a zinc importer protein is expressed, then fall as the cells mature. Not unexpectedly, importer levels rise, then fall, during cell development, whereas exporter levels rise and never fall. When they knocked down levels of the zinc exporter protein, zinc levels increased – and cells differentiated toward mature red blood cells more quickly. They refer to the carefully-timed changes in zinc transport protein levels as a “zinc transporter switch” that must be balanced to regulate zinc levels and allow for proper red blood cell development.
In addition to the oral presentations, UW Carbone researchers are presenting eight posters, and many others are attending the conference.