Many of the scientists featured in Discovery jump-started their independent research careers with an award from the Patrick C. Walsh Prostate Cancer Research Fund. In fact, some major urologic discoveries have been nurtured and made possible by this seed money.

Since its inception in 2005, this remarkable Fund – which owes its existence entirely to patients and friends of the Brady – has awarded millions of dollars to Johns Hopkins scientists with good ideas worth pursuing. Their research has produced better ways to detect, treat, and prevent prostate cancer. Applications are reviewed by a Scientific Advisory Board comprised of noted Hopkins scientists and lay members.

Scientist Karen Sfanos, Ph.D., has received three awards from this fund. All three have generated important, field-changing research. Her major area of expertise is the microbiome – the millions of bacteria that live in the gut, and also the urinary tract – and their influence on prostate cancer development, progression, and response to therapy.

Her first Walsh Fund award was in 2013 when she was just starting her career.

That research led to a key finding related to other Brady research on a cancer-causing substance called PhIP, found in charred meat: Sfanos and colleagues found that in mice that developed prostate cancer due to PhIP, “if you add a bacterial infection to the prostate, the combination of PhIP and infection accelerates the rate not only of prostate cancer, but other PhIP-related cancers,” she says.

At that time, the systemic effect of inflammation was a very new concept, Sfanos explains. This is what the seed money in the Walsh awards is designed to do: allow scientists to develop and test new ideas, and then, once vetted, leverage that research into larger, National Institutes of Health (NIH)-supported projects. “All of my Walsh Fund awards have been high-risk, high-reward.”

The next award came in 2016, for a project that, Sfanos says, also seemed quite unorthodox. Her interest in the role of infection in prostate cancer led her to wonder where that infection might be coming from. She suspected that bacteria were escaping into the prostate from the urinary tract – but at that time, no one thought this could be a possibility. “The whole concept of a urinary microbiome was completely controversial,” she says.

With this award, Sfanos provided further proof that urine is, in fact, not sterile. “Any part of the body that is exposed to air is colonized by microbes, and that absolutely is the case in the urinary tract,” she says. “Part of that Walsh Fund award used the very large sample sets from the biobank created by (the Brady’s late Director) Alan Partin M.D., Ph.D.” Working with Partin and the research team, Sfanos obtained urine samples from more than 100 prostate cancer patients treated at the Brady.

“This was the very first urinary microbiome study of prostate cancer,” and it was published in the Journal of Urology. “That paper was a bit controversial,” Sfanos recalls. “Reviewers weren’t thrilled with the concept. But it catalyzed an entire field of study. It’s amazing that the Walsh Fund reviewers were willing to fund such a novel idea. I don’t think I could have funded that study through other sources.” Her results were so strong that soon she received a prestigious V Scholar Award.

Her third Walsh Fund award is a study involving the gut microbiome. “Again, it’s an out-of-the-box question, a finding we stumbled on in the lab.” The study is based on a metabolite called equol, which is only made when soy products from the diet are converted by specific intestinal bacteria. “In the U.S., only about 30 percent of people make equol, but in Asian countries, where they eat a lot more soy, equol is much more commonly produced.” Equol has anti-androgen effects on prostate cells. “In in vitro models, this molecule can target the androgen receptor.”

Sfanos got interested in equol when she was conducting microbial profiling as part of the ORIOLE trial, led by former Hopkins radiation oncologist Phuoc Tran, M.D., Ph.D., which involved treating oligometastasis (only a few small areas of metastasis in prostate cancer) using SBRT radiation. “We found that patients harboring equol-producing bacteria had a lower risk of disease progression.” The scientists speculate that equol makes the cancer more susceptible to radiation.

“With our current award, we are studying this in a mouse model,” Sfanos says, looking at mice with prostate cancer who receive radiation alone, or radiation plus equol. “We are seeing greater tumor regression in mice that have the combination. Is there some influence on the immune system, as well?” She hopes to find out. “Aren’t gut bacteria amazing?”