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David Q. Matus, Ph.D.

David Matus, Ph.D., of Stony Brook University and recipient of an NIH K99/R00 award.

Credit: National Cancer Institute / David Matus, Ph.D.

Evolutionary developmental biologist David Q. Matus, Ph.D., is an assistant professor in the Biochemistry and Cell Biology Department at Stony Brook University in New York. He is interested in cellular invasion, a behavior observed in some normal cells during development and a hallmark of metastatic cancer cells.

Dr. Matus began his scientific career—and met his wife, Deirdre, also a biomedical scientist—while training dolphins in Hawaii as part of an internship on dolphin cognition. He decided to stay at University of Hawaii for graduate school, studying gene networks in sea anemones in the lab of Mark Q. Martindale, Ph.D.

Although his interests are broad, these days, Dr. Matus’ organism of choice is the nematode, Caenorhabditis elegans, a small translucent worm whose genetics and development are well understood. “C. elegans is great as a model for gene discovery of basic biological processes. The genetic control of programmed cell death and the genetic basis of aging were discovered in C. elegans,” he explained.

Because of the genetic tools available and the fact that the worm’s translucent body makes it easy to view under a light microscope, C. elegans lends itself well to Dr. Matus’ experiments. His work is aimed at understanding the molecular mechanisms of cellular invasion, which he studies in the context of the worm’s reproductive tract.

Optical section of spinning disc confocal micrograph showing C. elegans anchor cell (magenta) invading through the basement membrane (green).

Credit: National Cancer Institute / David Matus, Ph.D.

In the worm’s developing reproductive tract, a cell called the anchor cell directs the fate of vulval cells and neighboring uterine cells. The anchor cell also invades the basement membrane that initially separates the developing uterus from the vulva. Breaching this basement membrane is necessary to connect the uterus to the vulva, so that the worms can eventually lay eggs, Dr. Matus explained.

The cellular basement membrane is a thin dense sheet-like layer of tissue that separates the cells that line the cavities in the body from loose connective tissue underneath. Basement membranes are a unique innovation of the animal kingdom, found not only in worms but also in humans and all other animals, acting like a protective barrier and often preventing cancer cells from invading deeper tissues.

“The real strength of our system is that we can look at the invading cell and the basement membrane live, in vivo,” said Dr. Matus. “It’s a model to understand how to make a hole in a basement membrane.”

NCI awarded Dr. Matus a transitional award called the K99/R00, a grant intended to help young researchers transition to independent research careers. The aim of his research is to dissect the network of genes that control invasive behavior in the anchor cell.

He began the project while still a postdoctoral fellow in the lab of David Sherwood, Ph.D., at Duke University. While there, Dr. Matus conducted a genetic “screen”—a systematic method to identify which genes are involved in a biological phenomenon of interest—to identify genes necessary for invasion. He carried out the screen using a technique called RNA interference, which allowed him to knock down or turn off thousands of individual genes and observe which worms had defects in anchor cell invasion—and therefore which genes are necessary for the invasion process.

The screen allowed him to identify approximately 100 genes that play a role in anchor cell invasion, 95 of which had not been previously implicated in cancer metastasis. In collaboration with Stephen Weiss, M.D., a cancer biologist at the University of Michigan, Dr. Matus then carried out experiments that involved knocking down the human homologs of two of these genes in cell lines of human breast and colon carcinoma cells. The findings, published in Science Signaling in 2010, showed that turning off these genes prevented the cells from invading basement membranes, suggesting that they could be potential drug targets in metastatic cancer.   

Dr. Matus then focused his attention on genes called transcription factors, which control the expression of other genes. “You want to identify the transcription factors to lead you to their targets to help you understand basic principles about invasion,” he explained. “The goal is to understand the logic of how to program an invasive cell.”

Dr. Matus’ work led him to a transcription factor called Tailless, that, when lost, results in the normally singular anchor cell dividing. But, curiously, these mitotic cells fail to invade the basement membrane. Subsequent experiments showed that blocking cell division—putting cells in a state of rest, or quiescence—allowed for the expression of genes that the cells need to breach the basement membrane. “Invasion requires this quiescence in order to express the genes that are necessary to breach the basement membrane,” he explained.

Going forward, Dr. Matus plans to study anchor cell invasion in a variety of different nematode species, some separated by as much as 400 million years of evolution. “There are deep evolutionary roots in how you breach a basement membrane,” he said. “I think people just haven’t thought about specific cell behaviors associated with cancer, like cell invasion, in an evolutionary context before, and that’s what I’m really interested in.”

Dr. Matus’ interest in comparative evolutionary developmental biology comes, of course, from his academic lineage—a trace of which is carried in his name. When his Ph.D. advisor, Mark Q. Martindale, created Dr. Matus’ middle initial “Q” as a joke, it stuck. Now, Dr. Martindale’s students have also started to adopt the Q in their names. The shared middle initial is a testament to the strong bonds, both social and intellectual, shared by scientists connected to the Martindale lab.

As he moves on in his career, Dr. Matus is himself becoming a mentor. He’s started with his own daughters, Bria and Maile, ages 6 and 8. He helped the two fledgling scientists with their science fair project to decipher the color patterns of butterfly wings, a project which was inspired by the research of Nipam Patel, Ph.D., of the University of California, Berkeley. And in Dr. Matus’ lab at Stony Brook, he recently “passed the Q” to his first graduate student.

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