Researcher’s discovery could lead to blood test for breast and pancreatic cancers
If her husband hadn’t been transferred to Charlotte by Bank of America, Pinku Mukherjee would never have thought of working at UNC Charlotte.
But as she had twice before, she became the “trailing spouse,” following her husband’s career while raising two children and trying to build her own reputation as a scientist.
At 46, Mukherjee started over. She moved her lab, along with three associates, from Mayo to UNCC. And despite her reservations, she came brimming with ideas for experiments, looking for ways to outsmart tumors and possibly cure cancer.
Then in this unlikely place, Mukherjee’s winding road of a career came to a discovery that last spring won her the O. Max Gardner Award, the highest faculty honor given by the University of North Carolina system. It goes to those who have “made the greatest contribution to the welfare of the human race” during the year.
Pinku is, without question, one of the most committed and well-respected scientists in cancer research on the national arena today.
Anirban Maitra, a pancreatic cancer expert from M.D. Anderson Cancer Center in Texas
For Mukherjee, the turning point came in 2009. She was sitting in her office on the university campus when she got an urgent call from one of her lab associates:
You’ve got to come and see this.
Early interest in biology
Pinku Mukherjee (pronounced moo-KER-jee) has spent her life searching for explanations of how the human body works.
As a child in Bombay, India, she didn’t cry when she scraped her knee. She watched in awe as red blood cells formed “little blobs” that she later learned were clots. When she asked her mother about it, she was told, “That’s what happens. It just clots.”
But Pinku wanted to know more.
An only child, she took after her father, who loved teaching chemistry. He gave up that career for more lucrative work as a Bollywood film producer, but encouraged his daughter to follow her passion for science.
She collected multiple degrees – in microbiology, biochemistry and immunology – in Bombay and London. Then she moved to the United States in 1988 for more training at Pennsylvania State University, where her childhood sweetheart, Rahul Puri, was getting a doctorate in mechanical engineering.
Marriage and two babies followed. The couple moved for Puri’s career to Indiana and then Arizona. That’s where Mukherjee found what turned out to be a “dream job” at the Scottsdale campus of the Mayo Clinic. At the Minnesota-based health system whose name is synonymous with world-class medical care, she began researching the connection between cancer and the immune system.
“Things were starting to happen,” Mukherjee recalled. “Really good things.”
Then in 2006, after eight years in Arizona, her husband proposed another move – to Charlotte, the home office of his employer, Bank of America.
Mukherjee wasn’t happy about this idea, but she thought she found an answer. She would work at Duke University, where she was offered a job, and her husband could commute daily to work in Charlotte. They even put money down on a house in Chapel Hill.
But when she actually drove from Durham to Charlotte one night, in three hours of pouring rain, Mukherjee sobbed behind the wheel, realizing the distance was too great.
They changed their plans, stayed in Arizona, and Puri traveled back and forth to Charlotte for the next two years.
Meanwhile, he kept his eye out for jobs that might interest his wife. He knew she wouldn’t take just any position, and he wanted her to be happy. But he felt an urgency. He was close to their daughters, then in middle school and high school, and wanted to be around to help them with physics and math. If they could be together in Charlotte, he promised he would never ask his wife to move again.
In 2007, Puri came across an Internet ad for a new position in the biology department at UNCC – the Irwin Belk Endowed Professor of Cancer Research.
“It was almost like somebody looked at Pinku’s resume and said these are the requirements for the job,” he recalled.
He sent her application without even asking.
A team player
On the UNCC campus, Mukherjee’s resume created a buzz.
Mukherjee remembers getting a call from the late Michael Hudson, then biology chairman, who asked when she could start.
Not so fast, she thought. She needed to know more about this place.
Mukherjee checked around. She liked what she heard about UNCC’s ambitious plans for research. And even though Charlotte didn’t have a medical school, she was impressed by the collaboration between scientists at UNCC and Carolinas HealthCare System, the region’s large public hospital system.
Nancy Gutierrez, dean of the College of Liberal Arts and Sciences, remembers her interview with Mukherjee and being so charmed that she unintentionally dropped her typical professional demeanor.
“Oh, I love that coat,” Gutierrez recalled saying when Mukherjee walked in. And they spent the first few minutes talking about the scientist’s bright pink raincoat.
Gutierrez could tell that Mukherjee was not only smart and ambitious, she was humble and collaborative. She was just the kind of person Gutierrez was looking for – “Somebody who’s not just going to be a star, but also part of a team.”
Starting over at UNCC
In the summer of 2008, Mukherjee and her family moved to Charlotte. She also moved her lab.
To do that, she got invaluable help from two post-doc fellows and a lab manager who also chose to relocate their families to Charlotte so they could continue to work with their mentor.
They packed up hundreds of valuable laboratory mice in special ventilated containers for the cross-country flight. And once at UNCC, they bought centrifuges and refrigerators, petri dishes and microscopes for the new lab in Woodward Hall.
In a few months, Mukherjee took up where she had left off.
At the Mayo, she had worked with Sandra Gendler, a respected tumor biologist. Together they did experiments on mice to see if vaccines could prevent breast and pancreatic cancer. As part of that, Mukherjee began helping Gendler try to determine the role of a protein called MUC1 (muck-one) in the development of cancer.
MUC1 is a protein that’s present on the cells that line most organs. It lubricates and protects them.
But it also has a dark side. When cells become malignant, the MUC1 protein changes and signals tumor cells to multiply.
In their experiments, Gendler and Mukherjee tried to immunize mice against the abnormal MUC1 proteins, just like humans can be immunized against the flu. They injected the mice with vaccines, and as expected, their immune systems revved up for a fight. But instead of succumbing, the tumors continued to grow.
“Something in the tumors was not allowing the immune cells to go in and kill,” Mukherjee concluded.
As an immunologist, her goal became clear: To find a way to block that signal – and allow the immune cells to kill.
At UNCC, she came up with an idea. What about using an antibody?
Mukherjee knew the right antibody could lead straight to her target. Just like every lock has a single key, every antibody is unique and defends the body against a specific foreign body. If she could get to the right target, she might be able to figure out how to kill the tumor cells with their abnormal MUC1 proteins.
She didn’t have such an antibody. But that didn’t stop her.
“Heck,” she said, “let’s make our own.”
A simple experiment
To her, the plan was simple. She would use her mice and their own immune systems to create antibodies.
It’s the same thinking behind the emerging field of immunotherapy which has led to new “targeted” drugs that are giving unexpected years of survival to many cancer patients. Enthusiasm for this groundbreaking therapy is reflected in prime time TV ads that tout the benefits of Opdivo, a new drug that “works with your immune system” to treat lung cancer.
Researchers describe these new therapies as “smart bombs” that go directly to cancer cells, killing them without bothering surrounding healthy cells. That compares with traditional chemotherapy that kills whatever it touches, including healthy tissue.
Mukherjee wasn’t trying to make a drug. (At least not yet.) But, like the smart bombs, she was trying to target the tumor.
Her associates did much of the lab work. It was slow and deliberate. They took cells from tumors in sick mice and injected them into healthy mice. Then they watched. As cancer attacked the formerly healthy mice, their immune systems spewed antibodies to fight off the tumors.
The associates harvested these antibodies and grew even more in petri dishes. Once they identified the most effective antibody, they tested it again and again. They wanted to see if it could be relied upon to target the cancer cells every time, while leaving the surrounding healthy cells alone.
Then, one day in 2009, they called Mukherjee: You’ve got to come and see this.
She hurried down the hall, opened the locked double doors to the lab with her key card, and stepped up to the microscope. She saw what she had been hoping for.
Tumor cells were lit up in fluorescent green, signifying the antibody was binding to the abnormal MUC1 proteins – and ignoring the healthy cells.
Her antibody was hitting its target. Every time.
The next step was to test it on human blood.
For this part of the research, Mukherjee and her associates used samples from both healthy patients and cancer patients that were stored in the lab freezer.
They added the human blood samples to the new antibody. And again they watched for the reaction.
Sure enough, it consistently distinguished between malignant and healthy cells.
When Mukherjee saw the data, she thought: “Oh my gosh. This looks crazy good.”
That Friday night in October 2009, she and her husband poured glasses of red wine as they talked about their day. She got his attention when she told him her lab had tested 200 human blood samples and the antibody had shown nearly 100 percent accuracy.
Puri, an engineer good at analyzing data, remembers his reaction when he saw the numbers: Wow!
He stayed up all night, reading blogs and websites. The more he read about the need for diagnostic tests and cancer treatments, the more excited he got. At 5 a.m., he could no longer wait.
He woke her up and said: You have to start a company.
Coming to market
Mukherjee and Puri couldn’t stop talking about how they might apply her discovery to the real world.
Maybe the antibody could be used in cancer treatment, to help deliver one of those “smart bomb” drugs to destroy tumors.
Or maybe it could help with diagnosis, by showing which cells are benign and which are malignant. That might help detect cancer sooner, when it’s easier to treat. Or it might help rule out cancer, allowing patients to avoid unnecessary testing or treatments.
But scientific discoveries don’t automatically translate into marketable products. That can take years and lots of money. And many ventures fail.
Puri and Mukherjee didn’t have experience starting a biotechnology company, but they knew they needed to protect her discovery and control how it was used.
By 2011, with help from UNCC, Mukherjee got a patent on her antibody and created a company, now called OncoTab.
The going was slow. They began raising money – including the $50,000 grand prize she won in the Charlotte Venture Challenge. But with research, teaching and advising graduate students, Mukherjee didn’t have much time for the business.
Near the end of 2014, they had a decision to make.
Taking an opportunity
Although he’d spent his career in the corporate world, Rahul Puri had always wanted to start a business. He grew excited about the idea of working full-time on his wife’s project. He quit his job at Bank of America and took over as CEO of OncoTab.
The couple met with investment bankers about how to meet their fundraising goal – $3.5 million. They hired a Washington lawyer for guidance on getting regulatory approval.
Eventually they hope to find applications for multiple cancers, but for now, they are focused on producing a blood test to help diagnose breast cancer. They chose this because of the potential they see to help the 40 percent of women whose dense breast tissue causes mammograms to often miss cancers. They believe the blood test, as an adjunct to mammography, could help detect breast cancer earlier, when it’s easier to treat.
In October, the OncoTab laboratory got registered, meaning it can begin selling the blood test. It will be available to doctors, and to patients with prescriptions, in February at www.oncotab.com. The cost is about $150 per test.
Long way to go
Mukherjee looks back over these past seven years and finds it hard to believe how things have turned out.
Pinku Mukherjee received the 2015 O. Max Gardner Award and its $20,000 cash prize – the highest faculty honor given by the board of governors of the 17-campus University of North Carolina system. She is the second UNCC faculty member to win in the 66-year history of the award.
“I never thought we would be here, with a company and a test about to be launched,” she said. “It was completely serendipitous.”
Despite her initial skepticism about UNCC, Mukherjee quickly came to value the university’s commitment to research and her supportive colleagues.
Last spring, she brought acclaim to the Charlotte campus by winning the Gardner Award, with its $20,000 cash prize, from the board of governors of the 17-campus UNC system. In the award’s 66-year history, she’s only the second faculty member from UNCC to have won.
In a letter supporting her nomination, Anirban Maitra, a pancreatic cancer expert from M.D. Anderson Cancer Center in Texas, wrote: “Pinku is, without question, one of the most committed and well-respected scientists in cancer research on the national arena today.”
Dr. Kim Lyerly, the Duke cancer specialist who almost hired Mukherjee before she came to Charlotte, said her accomplishments have been “remarkable” at a university without a medical school. “What I’ve seen looks very promising,” Lyerly said. “But it’s only in retrospect that we’re going to know what kind of impact it’s going to have.”
In early December, Mukherjee and the OncoTab team traveled to San Antonio for an annual Breast Cancer Symposium that attracts 8,000 researchers and cancer survivors from more than 90 countries. They shared news about their blood test and heard about other cancer advances.
That put things in perspective. Hers is just one of many developments in the vast international arena of breast cancer research.
There is a long way to go. As the blood test rolls out, Mukherjee will be watching closely.
“It still weighs on my mind,” she said, “whether it’s really going to be good when you go out into the public with thousands and thousands of samples. Who knows? We don’t know.”
The challenge keeps her going. She has more questions to answer. It’s like an addiction.
“Cancer,” she said, “is always one step ahead of you.”
▪ Age: 53
▪ Grew up in Bombay (now Mumbai), India
▪ Married to Rahul Puri since January 1986; daughters, Priya, 23, pre-med student at the University of Pennsylvania, and Natasha, 21, molecular and cellular biology major at the University of California, Berkeley. Mukherjee’s 96-year-old father, Shankar Mukherjee, lives with the couple in Waxhaw.
▪ Undergraduate degree in microbiology and biochemistry, Bombay University; master’s degree and doctorate in immunology, University of London; post-doctoral fellowship, Pennsylvania State University.
▪ Currently Irwin Belk Endowed Distinguished Professor of Cancer Research at UNC Charlotte Department of Biological Sciences; founder of OncoTab, a biotech company. In August, she became interim chair of the UNCC Department of Biological Sciences.
▪ Received grants totaling more than $13 million from federal and private sources, including $4 million since coming to UNCC in 2008.
▪ Sings Bollywood-style music at Charlotte’s annual India Festival at Spirit Square and judges the Charlotte India Idol contest.