In life and in the lab, he never gives up

There was no hospital – there still isn’t – few people were educated past the sixth grade, and running water and electricity were luxuries that existed only in dreams.

Mani’s village of Sendurai is in Tamil Nadu, literally “land of the Tamils,” a state replete with an abundance of natural and man-made wonders. The monsoon-fed region features the Pillaiyarnatham rainforest near Sendurai, tiger and elephant reserves, endless beaches, prehistoric dinosaur nesting areas and soaring ancient Hindu temples – many of which are UNESCO World Heritage Sites. Mani’s world, however, revolved around his parents’ subsistence lifestyle.

“We had no expectations. We had no money. So we accepted what we had,” he says.

Acceptance included having just one name, common in parts of rural India. It wasn’t until he was much older that he took the name of his village as his given name. In his youth he was simply Mani.

Sleeping outdoors on a woven mat with his brothers was an accepted part of life as the son of a peanut farmer whose one acre also supported rice paddies, a milk cow, and a family destined to follow in the subsistence farming lifestyle that was the only world Mani knew.

“You see when it rained, we had to go indoors, and there was no place to sleep so we stayed up,” explains Mani, who is now an associate professor of Translational Molecular Pathology and renowned for his work on cancer metastasis.

A head for problem solving 

When Mani completed sixth grade, his parents took the unusual step of allowing him to pursue an additional four years of education in the nearby town of Melur, accompanying his Uncle Palanisamy, who would prove to be a constant mentor in the years ahead.

“In my village, if you fail in school, there is no going forward to further education. Fortunately, I did not fail,” Mani says, flashing an infectious smile.

In Melur, Mani was introduced to the English alphabet, but found using English in addition to his native Tamil to be challenging. He didn’t let that stop him. His parents’ wishes, however, were another story.

“At the end of 10th grade, my parents said ‘OK, you’re done with your education. It’s time to come home to the farm,’” Mani recalls.

With no money for further schooling, he returned home. Once again, his uncle stepped in with an offer to help him continue his education in Chinnalapatti, where Mani hoped to study mathematics and computer science.

But his lack of English sent him in another direction.

His path included some time studying botany, another return to his parents’ farm after completing the 12th grade and – at his uncle’s urging – college in Madurai, where he studied zoology.

After earning his undergraduate degree, Mani applied for a master’s program at several colleges and universities, but wasn’t accepted.

Eventually he entered the biology program at Kamaraj University in Madurai.

After Kamaraj, Mani was accepted into the Ph.D. program at the India Institute of Science in Bangalore. Like so much of his education, this seemed to happen by chance.

“There was one slot in the lab of a leading Indian genetic scientist, and the student who had been selected decided against coming, so I got his slot,” explains Mani.

It was in 1998 at the Indian Institute of Science where he met Robert Weinberg, Ph.D., one of the top cancer researchers in the world. The connection would change his life.

From Bangalore to MIT and MD Anderson 

Weinberg, an internationally known scientist whose work as a founding member of the Massachusetts Institute of Technology’s Whitehead Institute for Biomedical Research led to the hallmark discoveries of the first human oncogene – Ras – and the first tumor suppressor gene – Rb – had a penchant for mentoring brilliant young minds. Mani intuitively sensed that Weinberg was someone who would influence his career.

“He came to give a lecture at the Indian Institute of Science, and I made a point to introduce myself,” says Mani. “I asked to join his laboratory.”

Weinberg must have seen great promise in the young postdoctoral student. Upon meeting him, he asked Mani to “wait right there” when he was called away for a few minutes. When Weinberg returned – two hours later – Mani was still waiting.

“By the end of the day he offered me a position in his lab at the Massachusetts Institute of Technology (MIT).”

For Mani, MIT might as well have been Mars.

His understanding of the international science community was minimal. All he knew was that a truly great man had asked him to join his team. It was an event that would transform his life. But when he arrived at MIT’s Whitehead Institute, Mani wasn’t prepared for scientific study at a pre-eminent laboratory.

But within a short time Mani began to prove his merit. He worked with two colleagues looking at breast cancer metastasis and it intrigued him.

“I knew then that I wanted to determine what made cancer cells metastasize.”

In 2004, his team’s discovery of the Twist gene, a key player in metastasis, was published in Cell. Today, it continues to rank among Cell’s most-cited articles. By 2008, Mani was regularly interviewed by the media and was featured in a New York Times article that touched on the huge departure from his childhood “studying by kerosene lamp” to his work in Weinberg’s lab identifying similarities between cancer cells and stem cells. That work, which resulted in another landmark Cell article, could lead to new ways to stop cancer metastasis.

Mani joined MD Anderson in December 2007.

It was a move that allowed him to interact more closely with clinicians and to continue studying the biology of tumor initiation, invasion and metastasis.

His most recent work examines similarities between mouse embryos and metastatic tumors. This led to the discovery that tumors have gene expression signatures similar to mouse embryos at an early stage, when they are more prone to develop metastasis.

This first-of-its-kind signature stands out in its ability to predict metastasis in breast cancer patients by analyzing the bulk of the primary tumor, rather than residual tissues or scarce circulating tumor cells.

Today, as Mani continues to make significant contributions to understanding the molecular basis of how tumors progress, he relishes the atmosphere of collaboration at MD Anderson.

“I’m able to work closely with patients and also be a part of the clinical side of research, in addition to the laboratory work,” he says. “In general, MD Anderson seems to be accepting of both success and failure – as failure is often a stepping stone to success.”

The same year Mani came to work in Houston, he married well-known Indian actress Poornima Bhat, who is his “strong supporter.”

They have a 5-year-old daughter, Prisha.

Despite his scientific successes, Mani’s thoughts are never far from his Indian village roots. In 1998 he founded the Sakthi Foundation with his mentor Pradheepkumar Challiyil, whom he met at Madurai Kamaraj University. The foundation provides educational funds for young people in Sendurai, and offers eye camps for checkups and vision care.

When Mani visits the village, he offers the same advice he shares with his trainees at MD Anderson.

“I encourage them to go after their dreams. And to never give up.”