Brian Lannutti, Ph.D., with Megan Dillon, research technologist II

Building the Foundation For a Cure

Picture this: After working all night in the lab, the tired young researcher decided he’d look through his microscope one more time. Suddenly, his drooping eyes widened and he let out an excited yell. He couldn’t believe what he saw — it was the answer that he’d been looking for all along. In true Hollywood fashion, he had just discovered the cure to one of the most devastating diseases to ever befall mankind.

And that’s because Hollywood is the only place this sort of thing happens.

“When it comes to science,” says Brian Lannutti, Ph.D., a researcher at Puget Sound Blood Center, “the media and other people outside the field want the ‘magic bullet’ answer, but scientists know that it’s never that simple.

“We never look at it like that,” adds Dr. Lannutti, the recipient of a Leukemia Research Foundation “New Investigator’s Award.”

“My research has the potential to find therapeutic strategies to help with bleeding disorders and certain forms of leukemias,” he notes. “That’s the overall goal.

“Currently, my lab is investigating signaling pathways within cells,” he explains.

“Signaling pathways (of molecules) are how cells communicate with their environment and with other cells. These signals tell cells if they should divide, mature, migrate or die. Right now, these types of studies are important because many scientists are targeting these signaling pathways to identify with therapeutic targets to treat a variety of diseases. As with all types of scientific studies, we learn from each other’s results, which are really building blocks of knowledge. It’s science building on science.

“Hopefully, my lab’s research will give us all an even greater understanding of how these signaling pathways work.”

The Work
Dr. Lannutti’s research focuses on several interrelated projects that examine the growth and maturation of megakaryocytes (MK).

“These are the cells in bone marrow that produce platelets, which in turn, control bleeding,” he says. “I’m looking at specific signaling through specific pathways that are involved in megakaryocytopoiesis, the scientific term for megakaryocyte development.”

As he explains: “The long-term objectives are to gain an understanding of the molecular events controlling megakaryocytopoiesis by studying the genetic and signaling factors that control MK lineage commitment and the regulation of cell cycle during this process.”

Because precise regulation of platelet production is critical over the life of an organism and can be abnormal during the course of a disease, Dr. Lannutti will concentrate on the signaling pathways that are essential for optimal growth of MKs and platelets.

He will accomplish this by manipulating a group of enzymes known as kinases that control cell growth: “When you inhibit certain types of kinases (via chemical or genetic manipulation) within the cell, you get a hyperproliferative effect, meaning a higher rate of cell growth that can result in disease,” says Dr. Lannutti.

“In a simple view, it’s basically how leukemias develop. You’ll have uncontrolled proliferation of certain blood cell lineages, that arise from a clonal event. They fail to differentiate into a fully-developed cell; they just keep dividing.”

Instead of an MK’s developmentprogressing, abnormal terminal differentiation occurs, resulting in lowplatelet counts and abnormal plateletmorphology, which in turn results indiseases like thrombocytopenia.

“These studies will increase ourunderstanding of MKs developmentand the signaling pathways that control development, and thereby lead tocontrolling those diseases,” says Dr.Lannutti.

The Grant
The “Young Investigator’s Awardis a one-year career development grant for faculty members in theirfirst four years of their first academic appointment.

Dr. Lannutti is an Assistant Member of Puget Sound Blood Centerand a Research Assistant Professor at the University of Washington School of Medicine. He is in his firstyear on the faculty.