Love and Science

“He jumped in the car and said ‘Oh, I love this song’ and turned up the radio,” Stacy recalled. “And off we went.”

MORGANTOWN CALLING

At the party, Ed wowed his ex by claiming to remember her phone number from their youth. “That was apparently all it took to win me over,” said Stacy, laughing. The two exchanged phone calls and then went on a new first date over Christmas break. They rang in the holidays by watching “Scream.” Soon, they graduated college and got engaged. Ed decided he wasn’t done with academia. They moved to Boone, N.C., where Ed earned his master’s degree from Appalachian State University.

In 2001, the couple married, becoming the Pistillis, and left North Carolina for Morgantown. He had his eyes set on a Ph.D., and West Virginia University was calling, thanks to one person. Stephen Alway was then an associate professor in the Division of Exercise Physiology and his research, heavily funded by organizations such as the National Institutes of Health, focused on aging, muscle wasting and rehabilitation.

“I was all about research in applied muscle performance and muscle physiology,” Ed said. “I wanted to come work with and learn from Steve Alway in the lab, so I came here for that opportunity and experience.”

Meanwhile, Stacy found a niche grinding away at Applebee’s and working her way up from server to bartender to manager. All seemed like smooth sailing in Morgantown, until Stacy noticed the lump.

SOMETHING WASN'T RIGHT

Near the end of 2005, Stacy felt it — a lump on the breast. She was barely 30 and had no family history of breast cancer. Out of caution, she had it checked out. Given her age and medical history, a health provider told her it was nothing to worry about. But the lump stuck around into 2006. When Stacy called another doctor to schedule a routine visit, she mentioned, “Oh, by the way, I have this lump.” They responded, with a hint of urgency, “Can you come in today?”

She underwent a mammogram, ultrasound and biopsy. But, again, a doctor told her not to worry. The couple embarked on a cruise to celebrate Ed earning his doctoral degree and upon returning, doctors asked her to come in to get the lump removed. It was then that the sobering discovery was made: It was, in fact, cancer. “A very aggressive cancer called triple negative breast cancer,” as Stacy put it. It’s called “triple negative” because the cancer cells do not have estrogen, progesterone or HER2 receptors. This type also tends to grow and spread more quickly than other breast cancers.

“Several doctors had told us not to worry about it, but it just wouldn’t go away. I would feel it, and I’m like, I know my body and knew something wasn’t right.”

After two lumpectomies, Stacy started chemotherapy, followed by radiation.

“The oncologist didn’t pull any punches,” she said. “He said, ‘You’re young. You shouldn’t have cancer. So we’re going to throw the book at it and give you the most aggressive chemo we can.’”

On their fifth wedding anniversary, in a show of solidarity, Ed and Stacy shaved their heads together, just days before her hair was about to fall out completely.

With the help of their families, Stacy moved back to New Jersey to complete radiation treatment as Ed started a postdoctoral research position in Washington, D.C. – setting off a long-distance relationship for a year in which the couple saw each other on weekends.

In 2010, the cancer diagnosis grew distant in the rearview mirror, culminating with the birth of their daughter, Paige. A few months later, Stacy would surpass the five-year mark of remaining in remission – a milestone for patients, who are then considered cancer free.

LIFE TRANSFORMED TO THE LAB

Life took the Pistillis back to Morgantown in 2011 when Ed accepted a faculty position at WVU. He hoped to expand his area of research in neuromuscular disease and muscle fatigue back at his alma mater. Previously, Ed had manipulated a protein (Interleukin-15) — that proved to aid in muscle fatigue. He published a paper on the discovery and sought to leverage that momentum at WVU.

His goal didn’t gain much traction.

“I had many discussions with faculty but nothing took off,” he recalled.

An epiphany had lain in wait all this time. With cancer — and its various treatments and procedures — muscle fatigue had hit Stacy hard. She was physically exhausted leading up to her diagnosis. At her parents’ home, after chemo and during radiation, she could walk up only four steps at a time before having to sit and rest. So why not harness Ed’s research to help prevent and ease muscle fatigue in cancer patients?

“Cancer was the obvious research area to move into,” Ed said.

Ed took what he learned in the labs up to that point and applied it to muscle experiments to study cancer in mouse models. Ed injected mouse models with cells that developed breast cancer to see how the muscles responded. He wanted to explore whether he could remedy any resulting issues by manipulating the same protein.

“I found that muscles in these tumor-bearing mice fatigued at a faster rate, without overt changes in the weight of the muscle,” he said. “Breast cancer was causing effects on the way the muscles responded to low-force repeated muscle contractions, inducing greater muscle fatigue.”

But when manipulating the protein in mice, muscles became more resistant to fatigue.

Today he is conducting a clinical trial for a drug for breast cancer patients.

Ed credited one of his wife’s surgeons, Dr. Hannah Hazard- Jenkins, now director of the WVU Cancer Institute, with helping him lay the groundwork for his research.

“I went to her office one day with papers and all this information ready to make a pitch,” Ed recalled. “When I walk in, she says, ‘So, you want some biopsies? We can get you some biopsies.’ It was that simple. She made it easy for me to do research.”

A biopsy, in this case, involves extraction of a piece of muscle tissue from breast cancer patients to be examined for alterations in gene and protein networks.

For his research, Ed has collected sample muscle tissue from patients (with consent, obviously) undergoing a mastectomy, surgical removal of the breast in cancer patients.

Ed identified muscle changes in the early stages of cancer, a reaction to the disease historically not given attention to until the later stages.

“You see people lose a lot of muscle mass when they’re metastatic, or in the late stages of cancer,” he said. “If you remember, Patrick Swayze had lost a lot of body weight when there were pictures of him with pancreatic cancer. But we noticed that this muscle wasting was not happening in patients with stage 1 or stage 2 breast tumors, but indicators of muscle fatigue were apparent. It begins early on, before you can see it on the outside.”

Ed stressed the finding’s importance — the fatigue happens in muscles before the wasting happens in the later stages of the disease.

Since 2015, Ed has collected nearly 100 muscle biopsies. He and his fellow researchers have compared samples to those in patients without cancer.

In addition, Ed has conducted research by inserting human tumors into mice. The tumors in the mice would grow and change the muscles similarly to what happens in humans. The tumors, Ed said, converge on one protein in the body — PPARgamma — that helps regulate metabolism.

Several drugs exist that target PPAR-gamma – but only for the treatment of diabetes.

“We started treating the mice with a drug and it reversed the muscle wasting,” Ed said. “It reversed the genetic profile in the muscle and changed the metabolic pathways. From the perspective of the genetic composition of the muscle, it fixed everything.”

The drug utilized by Ed is pioglitazone, primarily used to control high blood sugar in type 2 diabetes patients.

An “off-target effect” of pioglitazone is that it stimulates pathways that promote function of the mitochondria in the muscles. Mitochondria, as they teach in biology, Ed noted, is the “powerhouse” of the cell. It’s the “energy producer.”

“We're treating breast cancer patients with this drug for two weeks leading to their mastectomy surgery. We're basically doing the same thing as we did in the tumor-bearing mice. We get a muscle biopsy of the pectoralis, and we do genetic sequencing to see if we can fix the genetic profile.”

The trial is ongoing and has only four patients currently enrolled, so it’s too early for substantive results. The study is now in a phase in which researchers are trying to identify proper dosage of the drug.

“To patients undergoing chemo and radiation, my hope is that we can help their muscles stay more functional,” Ed said.

NOT AGAIN

While Ed found his new calling in studying breast cancer, the unthinkable happened to Stacy. In 2018, a 12-year cancer survivor, Stacy was given bad news again after tiny spots were detected in her breast after an ultrasound and biopsy. It was a new breast cancer, ductal carcinoma in situ, or DCIS, not a recurrence of the original triple negative breast cancer.

“It was on the same side as my first cancer. The doctors recommended a mastectomy. I said, “OK. If we are doing mastectomy, we are doing both. It’s a matching set,” she joked.

Stacy opted for the double mastectomy to avoid any potential future diagnoses.

“Here I was, a 12-year survivor seeing doctors every six months and getting lots of mammograms and biopsies. I just couldn’t keep doing that. And I want to be around for my daughter.”

Ed praised the WVU Cancer Institute for providing him with the tools and resources to not only reinvent himself as a researcher, but to leave an imprint on enhancing the well-being of cancer patients.

“Having the infrastructure and support at the Cancer Institute to embark on this new journey happened so quickly,” Ed said. “I came here being only trained on the basic science side so it’s a really big deal to do what we’ve been able to do. Having the chance to treat patients is not something I thought I’d ever see.”

Editor’s note: The use of animals in this project was evaluated by WVU’s institutional animal care and use ethics committee. West Virginia University is voluntarily accredited by AAALAC, a national peer organization that establishes a global benchmark for animal well-being in science.