With more than 20 years of experience as a molecular and cell biologist—including over a decade as a breast cancer researcher, with a particular interest in racial disparity among breast cancer outcomes in the United States—Upper School science teacher Dr. Padmashree Rida has had plenty of opportunities to support other scientists.
Prior to joining Rowland Hall in 2021, Dr. Rida worked as a university research scientist, a role that offered her regular opportunities to advise graduate students working on original research and academic papers. A natural-born mentor, Dr. Rida has always enjoyed opportunities to help others blossom in their careers. But she’s also seen how disheartening it can be for scientists who, years into their professional journeys, realize that academic research—a field rife with opportunities for failure in everything from choosing the right hypothesis, to uncovering negative or inconclusive results, to the struggle of getting top-notch journals to publish work, to securing grants—isn’t for them. “There are no guaranteed returns in research; it’s always a gamble,” she said. “You can put in so many years to discover you were barking up the wrong tree.”
When Dr. Rida was invited to contribute to a special issue of the International Journal of Molecular Sciences, she saw an opportunity for a teaching experiment. What if she were to invite one of her Rowland Hall students to assist her? She thought it may be an ideal way to challenge a promising young scientist, exposing them not only to the processes, skills, and risks of real-world research, but also to the nature of scientific collaboration.
So in April, when Dr. Rida was invited to contribute to a special issue of the International Journal of Molecular Sciences (IJMS) focusing on hypoxia, a state of oxygen insufficiency in the body, she saw an opportunity for a teaching experiment. What if she were to invite one of her Rowland Hall students to assist her? She thought it may be an ideal way to challenge a promising young scientist, exposing them not only to the processes, skills, and risks of real-world research, but also to the nature of scientific collaboration, as Dr. Rida would be working closely with one of her long-standing collaborators, Dr. Nikita Jinna, and a group of Dr. Jinna’s colleagues from the City of Hope cancer treatment and research center to write the article. She thought the opportunity could be similar to an internship, allowing a student to try out a career option, risk-free, to get a sense of fit. “They could get their feet wet and ask if it’s for them,” she said.
For the student to do well in this project, though, they would have to have a certain set of skills: a strong biology background, of course, as well as the ability to critically read and write, as they would be reviewing dense academic materials, drawing conclusions, distilling insights, and synthesizing information. Dr. Rida saw these traits in Max Smart, then a senior in her Advanced Topics in Biology class.
“Dr. Rida recognized a project like this was perfect for me,” said Max, a Rowland Hall Lifer whose love of the natural world has driven his lifelong interest in the sciences, and who also loves to write. And Max recognized how valuable the experience could be. “I could tell this was a phenomenal opportunity,” he remembered. He said yes and, after completing finals in May, began assisting Dr. Rida, first by helping her and Dr. Jinna look into the role hypoxia may play in patient resistance to androgen receptor inhibition, a treatment option for some patients diagnosed with a particularly lethal type of breast cancer: triple-negative breast cancer (TNBC).
“When a person is diagnosed with breast cancer,” Max explained, “their tumor will be tested for three biomarkers: estrogen receptor, progesterone receptor, and high levels of human epidermal growth factor receptor 2.” The presence of any of these biomarkers means the tumor’s growth or ability to survive is dependent on a certain hormone or signaling molecule. By identifying that hormone or signal, a medical team can determine an appropriate course of treatment. However, in approximately 10 to 15 percent of cases, patients’ breast tumors test negative for all three biomarkers, resulting in a diagnosis of TNBC. Because these tumors have none of the well-established actionable biomarkers, they are harder to treat; consequently, these patients have a lower survival rate. TNBC also disproportionately affects Black women, contributing to the observed racial disparity in breast cancer outcomes in the United States.
While scientists are working on novel precision treatment options for TNBC, they still have a long way to go, particularly because many patients develop a resistance to existing treatments. Since many TNBC tumors are androgen-driven or androgen receptor-dependent—meaning they need the hormone androgen to grow or survive—therapies that target this signaling axis have been explored for their ability to stymie disease progression. “We knew that treatments that target the androgen receptor axis often work successfully for a short period, but most patients eventually develop resistance,” said Dr. Rida. “Consequently, their disease relapses or progresses, and when this happens, we don't have good next-line treatment options for such patients.”
The team decided to “gather evidence and make a compelling case that tumor cells’ multi-pronged adaptations to hypoxia were allowing them to resist treatments that target androgen signaling in TNBC.” They hoped their research would help shed light on how and why existing treatments fail, offer a broad view of study results on treatment options, and, because such therapeutic resistance is a problem for some other androgen-signaling-dependent cancers, make progress that could potentially have wide benefits.
As they researched, Dr. Rida, Dr. Jinna, and Max found that hypoxia may play a role in resistance to treatments that inhibit tumors’ androgen receptor signaling, because when tumor cells divide rapidly they deplete their immediate environment of oxygen—resulting in a state of hypoxia. This state induces profound gene expression changes in the cancer cells, which promote tumor cells’ survival and spur tumor evolution into a more aggressive form that is more likely to spread and resist treatments. This adaptation to hypoxia can also lead to the production of androgen receptor variants that are stuck in the “on” state, no longer requiring androgen stimulation in order to provoke cell proliferation. These variants are not susceptible to androgen-receptor targeting treatments, and their production leads to treatment resistance.
With several lines of evidence supporting their suspicions on hypoxia’s role in therapeutic resistance, the team decided to focus their IJMS article on the topic—to, as Dr. Rida explained, “gather evidence and make a compelling case that tumor cells’ multi-pronged adaptations to hypoxia were allowing them to resist treatments that target androgen signaling in TNBC.” They hoped their research would help shed light on how and why existing treatments fail, offer a broad view of study results on treatment options, and, because such therapeutic resistance is a problem for some other androgen-signaling-dependent cancers, make progress that could potentially have wide benefits. And though early evidence indicated a promising direction, as they began writing, Dr. Rida, heeding her own experience, made sure to set Max’s expectations. “There’s no guarantee we’ll find anything,” she remembered telling him, “but that’s the gamble with science.”
That gamble didn’t deter Max, though, who jumped enthusiastically into the project, even, he said, as he faced a series of steep learning curves—beginning with getting acquainted with science writing. After Dr. Rida taught him how to use PubMed, a biomedical literature database, to search for primary literature with clinical trial data, Max remembered initially feeling overwhelmed as he worked to make sense of the jargon, acronyms, and medical terminology within these studies. “These are serious medical publications; it’s no joke,” he said. “It was like hitting a brick wall right out the gate—every sentence is riddled with words that mean nothing to you.” But after Dr. Rida recommended that Max make lists of unfamiliar words, terms, or methods so they could discuss them together, he got better at understanding the complex material. “With Dr. Rida's help, it became second nature,” he remembered. “Her mentorship broke down that brick wall.”
That mentorship continued as Max was challenged in other ways. He had to learn, for instance, how to pull from hundreds of pages of information the hard data that can benefit cancer researchers, and leaned on Dr. Rida’s advice to give himself space to process complicated material before looking for gaps or clarity within it. He also learned from Dr. Rida the importance of reading the literature critically, as well as broadly, to avoid scientific siloing. “Reading broadly allows ideas from different domains to network in ways that allow us to see things anew or from different vantage points,” explained Dr. Rida. So, in addition to reviewing studies on androgen-dependent TNBC, Max looked at studies on androgen-dependent prostate cancer, which behaves similarly to androgen-dependent TNBC and, because it has been researched for longer, offers an array of data on drug options and combinations that might be able to help researchers find what he called the “golden treatment” for TNBC patients.
Getting Max on board with this collaboration taught him team science—and all good science these days is team science.—Dr. Padmashree Rida, science teacher
Additionally, Max learned firsthand the essential, though often tedious, nature of academic collaboration: how a group of researchers narrows a paper’s focus, finds consensus, reviews drafts prior to submission to a journal for peer review, and revises a manuscript to address reviewers’ feedback and concerns. By letting Max participate in the full process, Dr. Rida was helping to prepare him for success in a world in which the best scientists, no matter their fields or roles, need to be able to go beyond the scope of their individual disciplines to solve problems or create change collaboratively. “We teach science in class, but we don’t talk much about how science is really done, how science is disseminated, and the community behind it,” she said. “Getting Max on board with this collaboration taught him team science—and all good science these days is team science.”
It also taught him the joy of team success. After more than two months of collaborative researching, drafting, peer reviewing, revising, and waiting, “Adaptation to Hypoxia May Promote Therapeutic Resistance to Androgen Receptor Inhibition in Triple-Negative Breast Cancer” was published in IJMS on August 9. When asked what it felt like to see his name listed in an international science journal alongside his mentor’s and five City of Hope researchers only two months out of high school, Max said it was gratifying—but was quick to point out that that gratification went far beyond his personal benefits.
“I hope it’s going to play some small role in this field of research so we can get better treatments for people suffering from cancer,” he said. “If we helped just a tiny bit, that’s really gratifying.”
For Max, who will start at Middlebury College in January after taking a gap semester, it’s clear the experience will drive his professional decisions. Though he’s still deciding what he wants to study, working on this paper taught him how much he values using his passion for science and his love of writing—skills he worked on during his time at Rowland Hall—to help people. “I really appreciated being able to put knowledge and skills I’ve spent my entire academic career honing toward something that is actually going to, hopefully, play one tiny, small part in benefiting people who need good treatment,” said Max. “That was a pretty unique and awesome feeling.”
I really appreciated being able to put knowledge and skills I’ve spent my entire academic career honing toward something that is actually going to, hopefully, play one tiny, small part in benefiting people who need good treatment.—Max Smart ’22
For Dr. Rida, her self-described teaching experiment was also gratifying. Even before the rollout of Rowland Hall’s strategic priorities, she had been thinking about how she can harness her experience, resources, and background to give Upper School students opportunities to help find solutions to real-world problems and to participate in the construction of new knowledge. With this project under her belt, she’s even more aware of how she can best support them. “I learned so much about how to teach about clinical issues, to mentor, how students learn, what misconceptions they may have, and how to explain things,” she said of her time working with Max. She also learned how inspiring it can be to watch a high school student step up to a new challenge. “Max was willing to put in hours and hours of reading and writing, painstakingly plowing through literature,” she said. “Not once did he say, ‘I’m done.’”
And while she knows future experiences might not always be such a good fit, seeing how Max blossomed over their months together—his openness to new ideas, willingness to take risks, ability to successfully take feedback, and determination—showed her that offering them is worth the risk. Moreover, she knows such authentic learning experiences can impact young scientists’ identities, sense of belonging, and understanding of science. Thanks to this opportunity, Max took away an essential life lesson he’s grateful for—and one that will continue to give back to him, whether or not he becomes a researcher himself.
“I certainly got a taste of how some research can end up leaving you with very little to show. It can be discouraging. But then again, what isn't discouraging from time to time?” said Max. “It was an experience that helped teach me that anything you invest time and energy into can end up disappointing when it doesn't always pan out how you want. But when you hit those junctures, you just have to keep persevering.”