Dr. Ruth Scherz-Shouval
In order to execute the complex maneuvers of metastasizing and evading the body’s immune response, tumors need help. And they get that help from a surprising place: their healthy neighbors.
The noncancerous cells that surround cancer cells are known collectively as the tumor microenvironment, and include cells of the immune and blood systems and fibroblasts, which produce fibers such as collagen.
Cancer cells grow and survive by recruiting healthy cells from the microenvironment to help support them.
How the cancer cells are able to recruit the healthy cells to their cause is the source of intensive research – including by Dr. Ruth Scherz-Shouval of the Weizmann Institute of Science’s Department of Biomolecular Sciences, who says: “We want to understand the very early steps of how the cancer cells convince the cells of the microenvironment to support them and help them grow.”
“While cancer cells have mutations in their DNA, the cells of the tumor microenvironment do not,” continues Dr. Scherz-Shouval, who is working to unravel the mechanisms involved in the tumor cell-microenvironment connection. “We think that since the microenvironment cells don’t have mutations, it might be easier to develop strategies to reprogram them to become normal again than if we try to reprogram the cancer cells.”
During a postdoctoral fellowship at the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology (MIT), Dr. Scherz-Shouval zeroed in on something called the heat-shock response: when cells are under thermal stress, such as fever following inflammation, they activate this response. It is one of the protective pathways that cells have evolved to promote their survival under stressful conditions – and unfortunately, cancer successfully exploits some of these defense mechanisms, including the heat-shock response.
Dr. Scherz-Shouval identified a new role for the “master regulator” of the heat-shock response – heat-shock factor 1 (HSF1) – in the tumor microenvironment. She showed how HSF1 helps reprogram fibroblasts, the cells responsible for making the extracellular matrix and collagen in neighboring tissues, causing them to support the tumor’s growth. Clinical studies in collaboration with physicians at the Brigham and Women’s Hospital and Beth Israel Hospital in Boston, and at Rabin Medical Center in Israel, confirmed that, in early-stage breast and lung cancers, the activation of HSF1 in fibroblasts is strongly associated with poor patient outcomes.
One of the most challenging aspects of treating cancer is knowing how patients will respond. Now, Dr. Scherz-Shouval and her research team are investigating whether HSF1 activation in cancer cells can be used as a biomarker to predict a patient’s outcome and response to therapy. They are also looking at the role of other stress responses – such as hypoxia, or lack of oxygen – in the tumor microenvironment. to predict a patient's outcome and response to therapy
“Different stress responses are activated in different combinations in different types of cancer,” notes Dr. Scherz-Shouval. “So our goals going forward are to try to use these stress responses as biomarkers to predict patient outcomes in different types of cancer and to develop ways to therapeutically target these pathways.”
Dr. Scherz-Shouval earned a PhD in biological chemistry at the Institute, studying autophagy – the process by which cells discard or recycle defective or toxic materials. Even as a doctoral student, she made a major contribution to the field by unraveling a novel mechanism of autophagy regulation. She then completed a first postdoctoral fellowship in the Weizmann lab of cancer researcher Prof. Moshe Oren, legendary investigator of the p53 gene, before going to MIT for her second postdoc. Helpfully, she received a 2010 prize from Weizmann’s Israel National Postdoctoral Award Program for Advancing Women in Science, which provides funds so that outstanding women scientists and their families can move abroad for her postdoctoral studies.
Dr. Scherz-Shouval seeks to predict whether a patient’s cancer will respond to treatment – and to develop new therapies as well.
The award was created by the Weizmann Institute in 2007 to enable more women to successfully compete for faculty-track positions in academia. And instead of being earmarked for research, like many awards, the postdoctoral award aims to make everyday life easier for these hard-working, uprooted young scientists. Indeed, the support helped Dr. Scherz-Shouval, who is married to a physician and has three children, to pursue her MIT fellowship. “The grant allowed us to send our children to better schools and afford childcare for the extra hours that I could not be at home,” she says. In 2015, she returned to Israel with her family and joined the faculty of the Weizmann Institute.
Dr. Scherz-Shouval appreciates how the Weizmann Institute creates an environment conducive to both scientific discovery and family life. “I live on campus, so my lab, home, and the daycare center are all within a five-minute walk,” she says. “Everything that I want and need is right here.”
Living and working on campus is beneficial in many ways: “Some of the best collaborations” come from conversations on the playground.
She also appreciates the sense of community that the Institute fosters. “When I go to the swimming pool or the playground with my son, I meet up with my colleagues and some of the best collaborations emerge from those playground conversations,” she notes, adding: “The people and facilities are amazing, and I really think the Institute is the best place to do science in the world.”
Dr. Ruth Scherz-Shouval’s research is supported by the Laura Gurwin Flug Family Fund; the Peter and Patricia Gruber Awards; the Rising Tide Foundation; the Elsie and Marvin Dekelboum Family Foundation; the Comisaroff Family Trust; the Estate of Aliza Yemini; and the European Research Council. She is the incumbent of the Ernst and Kaethe Ascher Career Development Chair in Life Sciences.