Dynamic Duo Tackles Mechanisms of Gene Regulation

Dr. Robert Coleman and Dr. Wei-Li Liu met over a lab bench at UC Berkeley, where they were postdoctoral fellows, researching the mechanism within cells that regulates genes. She’d grown up in Taiwan and had developed an expertise in molecular biology. He was a biochemist, raised in suburban Philadelphia. They collaborated in scientific research, fell in love, and were married.

Dr. Robert ColemanBoth are now assistant professors in Einstein’s department of anatomy and structural biology. They arrived at Einstein during 2010, where they continue their research into the mysteries of gene regulation on the sixth floor of the Leo Forchheimer Medical Sciences Building.

The couple employs different techniques to study the action of genes: Dr. Liu uses high-resolution single particle cryo-electron microscopy, obtaining three-dimensioned images of proteins within cells; Dr. Coleman uses single-molecule fluorescence, which is able to capture moving images of the genes in action, both in vitro and within the complicated milieu of the cell.

“Our projects, like our personalities, complement each other,” said Dr. Coleman. “When Wei-Li’s technique is warranted, we use it, and at other times my technique can help get the answer. Many times we overlap. And that is what’s happening in science today: you can no longer rely on a single technique to get answers to your questions.”

Drs. Liu and Coleman developed their techniques in the UC Berkeley laboratory headed by Dr. Robert Tjian, president of the Howard Hughes Medical Institute. Their collaborators in Berkeley included Dr. Steven Chu, a Nobel Laureate in Physics who is currently serving as U.S. Secretary of Energy.

“Robert is looking at something more dynamic, while my images are static,” explained Dr. Liu. “It’s a powerful combination.”

The couple lives in Einstein’s Morris Park neighborhood, a short walk from their laboratory. “Living close by is important because we’re often in the lab from 9 a.m. to 8 p.m.,” said Dr. Coleman. “Science is not a 9-to-5 job.”

Their research focuses on the way genes faithfully transmit their DNA, or genetic code, to RNA, which is then read and translated into a protein. When the process works, cells are created and organisms develop in a healthy manner. But when cancer strikes, for example, that regulatory mechanism gets out of whack.

Dr. Wei-Li LiuThe duo looks at the basic science of these regulatory mechanisms, discerning how genes are turned on and off, and what happens in cancer and developmental genetic disorders, such as Huntington’s disease or Parkinson’s disease.

They conduct their studies using HeLa cells, the oldest and most commonly used human cell-line, which they brought from their Berkeley lab to the Bronx. “Scientists know the shape of the molecules they want to study, yet it can be difficult to isolate them,” noted Dr. Coleman. “One experiment may require up to 80 liters of HeLa cells, which take about a week to grow.”

“It’s a giant jigsaw puzzle,” he added. “We know what the pieces are and we are still trying to figure out how they all fit together.”

Dr. Liu’s interest in gene regulation evolved from her research into the machinery in cells that suppresses tumor growth. Using an electron microscope and complex data analysis, she can generate a three-dimensional image of the proteins from cells.

Since arriving in February, she has reached out to other Einstein researchers interested in learning her techniques. She is currently collaborating with Dr. Felipe Diaz-Griffero, assistant professor of microbiology & immunology, who is researching the biochemistry of the HIV-1 virus.

“Having a collaborative department was so important to me,” said Dr. Liu. “I was glad to bring my techniques here, and people have been very willing to help me.”

Both Drs. Liu and Coleman hope that their basic scientific research will one day lead to breakthroughs in gene therapy, helping to stop the spread of certain cancers or to halt the deterioration of the nervous system found in genetic disorders like Parkinson’s disease.

Such medical breakthroughs have deep personal meaning for Dr. Coleman; when he was a year old, his father was diagnosed with lymphatic lymphoma and given just six months to live. Mr. Coleman entered an early clinical trial and received chemotherapy treatments that sent his cancer into remission for 37 years.

He passed away in early 2010, on the day Dr. Coleman gave his first lecture at Einstein. “It was science that gave me a dad to grow up with,” he said. “I’ve always wanted to be scientist so I could give something back to science.”