UW News

November 6, 2003

New findings on platelet development and disorders

It’s been in all the newspapers, so you know it’s true: The style pages all tell us that the 70s and 80s are back. People are decorating with the color orange. Jon Bon Jovi is hot, hot, hot. And flared pants are the retro rage.

Another aspect of the ’70s and ’80s is back in science – but unlike the return of Bon Jovi or Ozzy Osbourne, this aspect may someday save lives.

Years ago, study of Src kinases, a type of enzyme, was all the rage. Scientists determined these kinases were oncogenes; in other words, when they mutated, they could become cancerous. And so a number of scientists studied Src (pronounced “sarc”) kinases in terms of cancer, and their role within the human cell. Journals were full of papers about Src kinases. But the pace of these studies died down, and scientists moved on to study enzymes that seemed, well, more contemporary.

But Src kinases remained on the scientific radar, and a few years ago, Dr. Jonathan Drachman added Src kinases to a petri dish as part of a hunch. He was curious what effect they might have on the growth of blood cells. As it was, they had a huge effect. Drachman will talk about his discovery and further progress for the next Science in Medicine New Investigator Lecture at noon on Thursday, Nov. 13, in Hogness Auditorium. The talk is free and open to the public. The title: “Src Kinases in Megakaryocyte Development.”

Drachman found that Src kinases might regulate the growth of megakaryocytes. Megakaryocytes are a kind of cell that saves your life every time you get a cut or wound. Megakaryocytes, which nest in bone marrow, produce platelets. Platelets play a key role in the astonishing process by which the body turns blood from a liquid to a solid in order to coagulate and clot a wound. Megakaryocytes thus help prevent your blood from just continuing to gush.

Drachman studies megakaryocytes because his research interests include inherited blood disorders. He focuses on uncovering the genetic and biochemical processes that regulate platelet production. His research has already resulted in a greater understanding of the causes of inherited blood disorders.

Drachman is an assistant professor in the Department of Medicine’s Division of Hematology, and a senior investigator at the Puget Sound Blood Center, where his lab is based. He is also a hematologist at UW Medical Center and the Seattle Cancer Care Alliance, where he has just helped establish a clinic for people with rare platelet disorders. (Hematology is the study of blood and its place in the body and in disease.) Drachman is a member of the American Society of Hematology and American Association for the Advancement of Science.

Drachman said there was never any doubt in his life that he would combine clinical practice with research: “In my clinical practice, I enjoy getting to know patients and building relationships with patients. Research offers something very different – the thrill of the discovery that lies just around the corner.”

Plus, if you will pardon the pun, science runs in his blood. Drachman can name a long list of relatives who are distinguished scientists in fields from physics to neurology at universities and government agencies including the National Institutes of Health. His father, Dr. Daniel Drachman, helped found the Department of Neurology at Johns Hopkins University in 1969. The department’s official list of scientific discoveries begins with accomplishments under Drachman’s name.

The younger Drachman earned his bachelor’s in biochemical sciences from Harvard in 1984 and received his M.D. from Harvard Medical School in 1989. His residency in internal medicine was performed at the UW from 1989 to 1991, and he was a fellow in oncology from 1991 to 1992. Drachman was chief resident of internal medicine from 1992 to 1993 and held a fellowship in molecular medicine and oncology at the UW from 1993 to 1996.

Drachman chose his specialty in part because he was inspired by Dr. Kenneth Kaushansky, a former UW professor of hematology now at the University of California, San Diego, and found a second home in his lab.

“Ken is a wonderful motivator and mentor. Research is 99 percent struggle and 1 percent excitement. Ken made you feel good even when an experiment failed, because he could always find lessons in any experiment and be ready to move on to the next step.”

Drachman emerged in 1998 from Kaushansky’s lab with two interests that now form the core of his own lab: the genetic mutations that lead to blood disorders, and signal transduction. Signal transduction is the process by which the body transforms a cell. For example, a chemical factor binds to a cell, enters the cell, changes the cell, and transforms the cell into an entirely different kind of cell. In some cases, the cell turns into a megakaryocyte, which draws the name ‘mega’ from its size. You can fit more than 500 red blood cells into one megakaryocyte.

Drachman’s laboratory seeks to uncover signal transduction pathways activated by thrombopoietin, the primary protein responsible for regulating platelet production, which was identified by Kaushansky while he was at UW. Perhaps partly because Src kinases were yesterday’s news, NIH reviewers were skeptical in 1999 when Drachman said he wanted to study the kinases’ role in blood cell production. It’s no easy task; for one thing, there are eight different Src kinases and they interact even with each other in complex ways. But his subsequent studies have shown that if you block Src kinases in an experiment, megakaryocytes grow faster. It may be that people with blood disorders have too much going on with their Src kinases. If so, then it might be possible to design therapies that address this imbalance, and help patients, Drachman said. Inn his Nov. 13 lecture, he will discuss the critical role played by members of the Src kinase family in normal and abnormal megakaryocytes.

“From a research perspective, Src kinases are old, and yet very new. They continue to surprise and challenge us,” Drachman said.