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SLAS2019 Keynote Speaker Teresa Woodruff: Life Sciences Research Gives Birth to Oncofertility

She explores the mystery of fertility, designing first a bioprosthetic ovary that restores ovarian function in sterilized mice, then creating a 28-day ovarian cycle-on-a-chip. Wielding her influence over United States health policy, this mover and shaker evaluates how research is conducted and what it can yield to fulfill urgent, unmet needs. Next, she addresses the SLAS community as keynote speaker at SLAS2019, Feb. 2-6, 2019, in Washington, DC.

She could simply have been a women’s rights crusader or an activist in Washington, DC. As director of the Women’s Health Research Institute at Northwestern University Feinberg School of Medicine (Evanston, IL), Teresa K. Woodruff, Ph.D., does both as she devotes herself to reproductive science.

For Woodruff, reproductive science represents a big open area for investigation–particularly where it collides with cancer treatment. “Life-preserving, but fertility-threatening, cancer treatments sterilize young women every day. About 12,500 cancer patients each year, who are younger than 12, face infertility, the inability to go through puberty and early menopause because of the chemotherapy and radiation used to fight their disease,” says Woodruff.

“As our cancer colleagues develop more and better treatments for cancer, earlier diagnostics and more use of surgery, we’ve been treating an increasing number of young cancer patients for fertility issues,” she continues. “We have an opportunity to change a devastating diagnosis with life-affirming interventions. These young cancer patients are the reason I have passion for my work, and I’ve never changed fields.”

Woodruff coined the term “oncofertility” to describe the medical field that she pioneers, and it is the focus of her presentation, “Bench to Bedside to Babies,” at SLAS2019. “I plan to share the new technologies our lab develops that lead to live offspring,” Woodruff says. These feats of engineering include: the Evatar, a menstrual cycle on-a-chip used to test drug toxicity, a 3D printed, bioprosthetic ovary that restores fertility in mice, and the discovery of the zinc spark–an inorganic signature of human egg activation. Woodruff earned “Discoveries of the Year” nominations from Discover magazine for the zinc spark in 2016 and for the bioprosthetic ovary in 2017.

“Pivoting between basic and applied aspects of the problems we’re trying to solve and the engineered solutions to meet those needs is what SLAS is about to me,” says Woodruff. “It is an interesting community and I’m delighted to be a part of it.”

Toward the Future, Moving out of the Biology of the Past

“What excites me about reproduction is how little we knew about the female ovary. All the fertility that we will have as women is present in that tissue at the time of our birth,” explains Woodruff, who fell in love with the science as a graduate student at Northwestern in the mid-1980s. “The individual oocytes are lost progressively until menopause. We know almost nothing about how each individual follicle–of about a million-follicle pool–decides to activate in a particular month. Maybe when a woman is 19 and it’s May, for example, the set of follicles begins the process of development, but one sitting right next to those activated follicles won’t begin that process for 10 or 20 years. This is what captivated me in the beginning.”

The first of her recent discoveries was the zinc spark, a spark or flash phenomenon that occurs in a halo around maturing eggs as they expel the mineral zinc after being injected with sperm like enzymes. In previous experiments with mouse eggs, the team detected more intense flashes for higher-quality fertilized eggs. “This process provides a good index for the developmental competence of that oocyte,” Woodruff says.

She then became interested in generating organ replacements for tissues lost during cancer treatment. Using bioinks, her team 3D printed microporous hydrogel scaffolds to house immature eggs and test how varying pore geometry, accomplished by manipulating the advancing angle between printed layers, affects the survival of ovarian follicles.

The team discovered that as the amount of scaffold interaction increases, follicle spreading is limited and egg survival increases. Follicle-seeded scaffolds become highly vascularized and ovarian function is fully restored when implanted in surgically sterilized mice. The bioprosthetic ovary built from these scaffolds boosts hormone production and allows the mice to go through puberty, begin ovulation and have offspring. The ovaries, shown to have long-term, durable function, represent the foundational work for what will be translated directly into patients, Woodruff says.

In another research endeavor, Woodruff’s team developed the Evatar, which has a functional reproductive tract that includes small 3D organ models of the ovary, fallopian tube, uterus and cervix.

Dubbed “the mother of all microHumans” by Woodruff’s lab, the Evatar also has a liver, which, while not part of the reproductive tract, plays a major role in the metabolism of ovarian hormones, as well as external drugs. The versatile chip features channels necessary to pump nutrients between its organs, produces and responds to hormones, has a normal 28-day hormone cycle and metabolizes drugs to reveal to scientists how a drug may affect fertility in women, or if it is toxic to the liver.

Since Evatar's organs are mostly made from human cells, she anticipates that personalized models can be made for each patient in the future. If a patient, for example, is diagnosed with uterine cancer, the lab could use the patient’s cells to make a model of her specific cancer and test drugs that would work for her.

“We have used static culture, such as petri dishes, just like every laboratory on the planet uses, but I’m convinced that petri dishes are the biology of our past,” Woodruff says. “Microfluidics are the biology of our future, primarily because our organs are connected together in a microfluidic system that happens to be our blood vessels.

“Evatar will lead to a whole new revolution that will be disruptive to what we do now on static culture. It allows us to take organs, such as the intact ovary, ovarian constructs or the artificial ovaries that we are creating, put them in a dynamic organ-on-a-chip system that can support the maturation of the 3D printed follicles for 30 days outside the body, and be functional for enough time to study them. It’s a game changer,” Woodruff continues.

She is inspired by science at the interface of reproductive biology, bioengineering and true engineering, “where hardware such as the Evatar is created,” she says. “I hope to develop more interactive science in the future.”

In the end, however, for Woodruff it comes down to patient impact that makes the difference. “Our inspiration are the patients in whose interest we work. I think the promise of science and basic medicine is that tomorrow’s patient will be treated better than today’s,” says Woodruff. “Our hope is for that little two-year-old or four-year-old child who is banking on our advances to be ready for their need either at the time of puberty or later for their fertility.”

An Advocate for Research Representation

Woodruff, while deeply engaged with scientific research, has always been equally passionate about how science impacts lives outside the laboratory. From her early post-doctoral days on the industry side of drug discovery in the late 1980s, she had concerns about how life sciences research was conducted. “Why weren’t the sexes weren’t equally represented in experiment?” she questioned. “How would the inclusion of female cells and female test subjects–both animal and human–impact drug discovery?”

According to Woodruff, 80 percent of basic science papers published at the time, featured research conducted only on males. She points to a U.S. Government Accountability Office report, which revealed that 8 of 10 drugs withdrawn from the market between 1997 and 2001 posed greater health risks to women than men. Woodruff commented in a recent radio interview on Chicago Public Media that life sciences research, “talks about time, temperature and dose; we just don’t talk about sex."

Woodruff’s efforts to raise awareness of the situation eventually persuaded the National Institutes of Health (NIH) to change policy in 2016, when the NIH declared that females–both animals and people–must be considered in all NIH-funded studies.

Beyond this work, her advocacy stretches from defending life sciences research’s use of parthenotes (unfertilized egg cells artificially activated with chemicals to divide) to examining environmental contaminant’s impact on fertility and reporting such information to the U.S. Environmental Protection Agency (EPA).

Woodruff, who appeared on Time magazine’s list of most influential people and received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring at the White House from President Barack Obama in 2011, also founded and leads the international Oncofertility Consortium. Based at Northwestern, the interdisciplinary initiative includes members in 117 countries and addresses the complex health care and quality-of-life issues that concern young cancer patients whose fertility may be threatened by their disease or its treatment.

And as one would expect of an academic lab, much of Woodruff’s time and energy is poured into educating–but not just graduate and post-doc students. Her Reprotopia project provides targeted reproductive educational opportunities for everyone from kindergarten through high school and adult learning.

Despite her busy hours, Woodruff finds time for what she refers to a the three “Cs”: the Chicago Cubs, the Chicago Symphony Orchestra and cooking. “These are the three things that my family and I love. This summer, we enjoyed a CSO performance that featured renowned cellist Yo-Yo Ma, reveled in numerous baseball outings and relished cooking for our entire family for Father’s Day,” she says, adding that the group included her husband, two step children, their spouses and two grandchildren. “The Cubs keep us interested year round–not only during the regular season, but in the off season. That’s what kind of die-hard fans we are!”

Advice from the Academic to All Walks of Life Sciences

“Be involved,” says Woodruff. “The more I do, the more I find ways to implement whatever I’ve learned from that committee or that connection that I’ve made. It actually furthers my career.”

She also encourages life sciences professionals to create a strong visual for their career–and that image should not be a ladder. “A career ladder, as you can imagine, can get tipped over. Be much broader, much bolder. I see the career as a lattice, where we reach out to different nodes that are part of an intricate network. A lattice is intrinsically stronger than a ladder,” says Woodruff, advising researchers to move beyond their scientific discipline to explore other fields. “The more connections we make, the more successful we’ll be.”

Woodruff’s further advice, for those embarking on academic research, is to invent, improve and implement. “You must invent solutions that people need to problems that represent urgent unmet needs, improve on the idea to the point in which it works and then implement that idea–don’t just have a paper about your research,” she says. “Too often academic researchers go between grants and papers and grants again. I think that’s a mobius loop. To escape the gravitational forces of that cycle, academic scientists need to implement. They must find utility,” she says.

Regardless of where one’s path leads in life sciences, Woodruff notes that scientists should be prepared to be plagued by doubt from time to time. “I think everyone at some point in their careers wonder if they’re going to make it. I tell folks to keep an eye on the next step. If you’re assured of that next step, take it. Eventually you can look back and see the entire pathway,” she says. “If you’re looking too much toward the future, you might miss one of the next footholds that you will need to be successful.”

September 10, 2018