A Mysterious Cell Behind Deadly Forms of Anemia
Dr. Orozco joined BRI’s Hamerman Lab just before Dr. Hamerman and Holly Akilesh, PhD, discovered iHPCs in 2019. They were investigating a rare but deadly complication of lupus and other rheumatic diseases called macrophage activation syndrome (MAS).
Their research revealed a new cell type that was supposed to eat up dangerous bacteria but was instead eating healthy red blood cells and causing life-threatening anemia.
Curious to learn if iHPCs are involved in other types of anemia, Dr. Hamerman partnered with a malaria expert at the University of Washington. They observed iHPCs doing the exact same thing in severe malarial anemia.
Ever since, Dr. Orozco and the Hamerman Lab team have been working to better understand where iHPCs come from and how to stop them from causing dangerous anemias.
Advanced Tools Provide Crucial Details
One of Dr. Orozco’s recent studies revealed an interesting pattern: iHPCs in the spleen seemed to cause far more damage than those in the blood.
“Something was obviously going on, but with the tools we were using, we could only collect a few data points,” she says. “We didn’t have enough information to understand exactly what was happening or why.”
Single-cell RNA sequencing and bulk-RNA sequencing will enable her to collect more data than ever before. These tools can provide information about every piece of RNA inside the iHPCs as well as their thousands of genes.
“The goal of any basic biology study is to understand what’s going wrong, so we can fix it. But we can’t fix it unless we know what’s broken,” Dr. Orozco says.
These tools enable the research team to tease out very specific details that could lead to important answers.
“It’s like an entire orchestra is playing but you can isolate just the sound of the second violin,” Dr. DeBerg says.
Steps Toward Answers
Not all scientists know how to use advanced computational tools to analyze big datasets like those from single-cell RNA sequencing. Instead, they partner with experts like Dr. DeBerg to analyze their data. But when scientists build their computational skills, it helps them to not only find the right answers but to also ask the right questions.
“Building computational skills helps you develop more intuition into what sorts of questions are easy or difficult to answer. It helps you know what questions are realistic with the data you have” Dr. DeBerg says. “And that accelerates the pace of discovery.”
Dr. Orozco is getting her experiment up and running and is excited to pursue a skillset she finds so fascinating during actual work hours. She keeps Dr. DeBerg on her toes by asking thought-provoking questions.
Their ultimate goal? Help people avoid severe complications of malaria and rheumatic diseases.
“Every incremental finding moves us a little closer to that goal. In the meantime, we’re sharing the knowledge we generate so any scientist can use that information to build upon” Dr. Orozco says. “Autoimmune diseases and malaria are very different, but we see this cell showing up in complications of both. We hope other scientists will see our findings, build upon them, and seek answers that we never would have thought about.”