Faculty Profile: Ronen Marmorstein, Ph.D.

Faculty Profile: Ronen Marmorstein, Ph.D.

Ronen Marmorstein, Ph.D.Ronen Marmorstein, Ph.D. worked his way up from the very bottom rung. Literally.

As a graduate student at the University of Chicago, he was part of one of the first research labs using X-ray crystallography, a process that reveals the three-dimensional structure of molecules, to study how proteins interact with DNA.

“I was the low man on the totem pole. I did all the biochemical work that led to the X-ray crystal structure but never actually got to do the structure myself,” Marmorstein said.
That didn’t come until a postdoctoral fellowship at Harvard University where he learned how to produce the structures – and the technology has improved much more since.

“The methodology and computation has improved,” he said. “So now one person completes the project from soup to nuts,” which is how members of the Marmorstein laboratory work today.

Marmorstein is the Hilary Koprowski, M.D. Professor and Program Leader of the Gene Expression and Regulation Program at The Wistar Institute.

His research exploits the use of X-ray crystallography and other complementary biochemical techniques to study
proteins involved in epigenetics, and how signaling molecules, like protein kinases, direct epigenetic programs.
“Epigenetic differences are what causes cells that have identical genetic information to do different things,” Marmorstein said. It’s what makes one cell a skin cell and another a stomach cell, for example.

[In the image: The Marmorstein lab uses X-ray crystallography to “see” the shape of the molecules they study. As X-rays bounce off of a crystallized form of the molecule(s) they study, they create a pattern (image 1) that can then be analyzed to create a computer model. The model (image 2) shows how a molecular inhibitor (yellow) binds to the active site of an enzyme (blue). The model helps the lab better understand how such small molecule inhibitors can be developed into useful drugs.]
Image 1Image 2

“The molecular basis for how this occurs is poorly understood,” Marmorstein said, and diseases like cancer, metabolic disorders or neuropathies are often mediated by epigenetic factors gone awry.

If researchers can understand the molecular basis for such misregulation, they can create drugs for epigenetic targets that could hopefully fix the disease.

Marmorstein, who was born in Israel and raised in New York, came to Wistar to start his own laboratory in 1994.
“The science at Wistar was exciting, the Philadelphia research community was vibrant and interactive and the graduate students were talented,” he said, thus drawing him to relocate here. “This all turned out to be true.”

Marmorstein lives in Swarthmore with his wife, Shoshanna Gottleib, who he met while in graduate school and who is now a middle school biology teacher, and their three children. His oldest daughter Anna is studying advertising at Penn State while his 17-year-old son Andrew, who worked in the lab with Marmorstein last summer, will be headed to Case-Western University in the fall to study engineering.

Word is still out on what their 12-year old son Jason will do, but he wants to be a baseball player. “He’s really into baseball right now,” said Marmorstein, who admits that his alternate dream job would be as a baseball player – even if he is outnumbered in his house and his adopted city as a Yankees fan.

“Jason is a Yankees fan,” he said. “But I was not able to convert the rest of the family. That will never happen – they’re Phillies fans.”