Dr. Anat Zimmer receives AAUW fellowship

Building a better biopsy

As a member of the Ha Lab, Zimmer focuses on cancer genomics, trying to detect and characterize cancers from tiny bits of cell-free DNA that have escaped from a tumor. Traditionally, biopsies are used to determine the biology of the tumors and identify the proper treatment. But biopsies can be invasive, occasionally unsuccessful and, in some cases, impossible to perform.

“Usually in order to monitor patients and their tumors, you use images and other measurements — repeated biopsies are not commonly used,” Zimmer said. “There are many good reasons why we want to replace this method of biopsy with an easier, less invasive and cheaper system that would be much nicer for the patient.”

Different types of these blood tests or “liquid biopsies” are rapidly entering the consumer marketplace, but they’ve yet to go through a rigorous scientific evaluation.

That’s where Fred Hutch researchers come in.

“What we are trying to do in our lab is detect the DNA from the tumor cells that are shed into the bloodstream,” Zimmer said. “Most companies and labs focus on the genomic alterations of tumor DNA since the tumor DNA is different than the rest of the cells of the body, using it for cancer detection. What we do is take it one step farther: we’re trying to characterize the tumor and trying to understand the transcription regulation from the DNA.”

A transcriptome is the complete set of RNA molecules expressed in a given entity, such as a cell. Transcriptomic profiling provides comprehensive information regarding the expression of mRNA or messenger RNA — the instructions that tell cells what proteins to build — in a given cell population.

“With this information, it’s possible to determine what parts of the genome are actively being transcribed and what parts are being silenced,” Zimmer said. “From that, we can get the molecular characterization of the tumor and we can use this information for precision oncology to treat the individual patient.”

Predicting prostate cancer treatment resistance

Zimmer is currently investigating the use of liquid biopsies to measure the levels of a type of variant associated with prostate cancer progression.

“The androgen receptor signaling pathway is highly important in prostate cancer,” she said, explaining that it has over 22 RNA splicing variants and one particular variant — androgen receptor splice variant 7, or ARv7 — that is “correlated and associated with response to treatment.”

“What we want to do is be able to measure the levels of this variant in a non-invasive way,” she said. “And we’re trying to do it from blood biopsies. We’re hoping to quantify and identify levels of this splicing variant from liquid biopsies.”

Zimmer and her lab mates are working with patient-derived xenograft, or PDX mouse models at present (mice implanted with human tumor cells).

So far, the analysis is going well.

“We’re able to distinguish between samples that are high and low in PDX mouse models,” she said. “We train the models, learn the differences between high V7 and low V7 in PDX lines and we apply the model on human samples.”

When will this translate to a test that can be done by a clinician on a prostate cancer patient?

“It’s hard to know when it will be available to everybody,” she said. “But non-therapeutics [like this] are usually easier and faster to be approved. We are working with doctors now who are already using this information with permission from their patients.”

Even more promising, Zimmer said splicing variants are not specific to prostate cancer. There are other types of cancers where a difference in splicing variants is associated with different outcomes and different responses to treatment.

“My plan — my dream — is that I will be able to show that this works on the androgen receptor in prostate cancer and that we can also apply it to different types of cancer,” she said. “But we are still far from that.”

Zimmer said Ha’s approach to researching treatment-resistant cancer was one of things that appealed to her when she first interviewed at Fred Hutch.

“I was intrigued by the idea of analyzing genomes, I’d never done that before, and I also liked the idea of cell-free DNA and inferring transcriptomics from DNA,” she said. “Most companies try to detect the genomic alterations, but Gavin Ha’s lab is more innovative. They’re taking it one step further.”

Taking science a step further

When it comes to communicating science, Zimmer does much the same.

In addition to conducting research in Israel, she also lectured at high schools and community centers and shared science with nonscientists everywhere from pubs to prisons.

“We used to go to bars in Tel Aviv and other big cities and give a talks in the bar,” she said. “I went to a correctional facility for women and lectured. You’d hear their stories and realize each and every one was in a horrible position — screaming for help but nobody would help them. It was so important to establish a connection with them, to provide them with education, to help them come back to life.”

Promoting women wherever they are is crucial to Zimmer — one reason she is so grateful for the support she’s received from the AAUW.

As a mother of three, she’s juggled multiple roles over the years, particularly the last few.

“I moved my family from Israel to the U.S. and that was not an easy move,” she said. “My husband had to let go of his career. And the expenses in Seattle are not what we’re used to. When you look at science and the steps in a career — first a Masters, then a PhD, then a postdoc, and then a position as a principal investigator, you see women less and less. That’s because we are mothers and those steps become very, very difficult.”

The AAUW award, she said, will make a huge difference in her being able to move forward with her career. Since its inception in 1888, the AAUW has awarded $135 million in fellowships, grants and awards to 13,000 women from 150 countries.

“I’m very grateful for the opportunity to be here and learn from the scientists at Fred Hutch and incredibly honored to receive this generous award from AAUW,” she said.