Harikrishna Nakshatri, PhD, BVSc, has made his mark on the field of breast cancer research as the Marion J. Morrison Professor of Breast Cancer Research at the Indiana University School of Medicine, but it’s a far cry from how his career began.
In fact, Nakshatri’s first foray into medicine didn’t involve working with human patients.
Raised in the village of Karkada, India, Nakshatri was the only one of his siblings to pursue higher education. His effort and performance in school landed him opportunities in a variety of fields, including engineering, but he ultimately chose to pursue veterinary medicine. That choice came with additional financial assistance from the Indian government, which, combined with funding provided by his brother, made it the clear best option to Nakshatri.
He studied veterinary medicine at what was then known as the Mysore Veterinary College in Bangalore, India, and went into practice as a vet for four years.
One of the more persistent issues Nakshatri encountered as a veterinarian was corpus luteum cysts in cows, which affected their hormonal signaling associated with the menstrual cycle. Farmers would bring in cows that appeared fully healthy but experienced persistent issues with infertility, which meant they wouldn’t be able to produce milk. These cows were ultimately able to become pregnant once Nakshatri operated and removed the cysts.
This happened so frequently that Nakshatri developed an interest in the hormonal signaling process and sought to learn more, pursuing his PhD at Memorial University of Newfoundland in Canada, engaging in post-doctoral work at Louis Pasteur University in France and taking on a staff scientist position at The Picower Institute for Medical Research in New York.
Then, in 1995, he saw a posting for a breast cancer research position at the IU School of Medicine.
“I applied, I got selected, I came here January 1996 and never left,” said Nakshatri, who is also the chief scientific officer at the Susan G. Komen Tissue Bank and a researcher with the Vera Bradley Foundation Center for Breast Cancer Research at the IU Melvin and Bren Simon Comprehensive Cancer Center.
National achievements and impact
Nakshatri’s list of achievements over the past 29 years is lengthy. He was named a fellow of the American Association for the Advancement of Science in 2021 and a Susan G. Komen for the Cure Scholar from 2010-2020 and again in 2023. He currently serves as president of the Cancer Biology Training Consortium, a national cancer research training organization. Additionally, he has authored more than 170 publications. Nakshatri’s research group was the first to identify the role of the signaling molecule NF-kappaB, which is active in triple negative breast cancer, and found another molecule known as AKT, which is responsible for resistance to a commonly used anti-estrogen treatment for breast cancer.
What’s kept him at the IU School of Medicine for almost three decades, Nakshatri said, are valuable research resources and the collaborative environment between his colleagues and key clinical partners like IU Health and Eskenazi Health.
“We don’t have a separation between the basic research and the clinicians,” Nakshatri said. “A lot of my work is guided by my repeated interactions with our clinicians.”
He emphasizes the importance of the Komen Tissue Bank, the only repository in the world for normal breast tissue and other samples. These normal samples can be compared with cancerous tissue, providing valuable insight into the processes behind cancer and its development. His group developed a single-cell atlas of the breast tissues of healthy women, which is now a global resource for scientists and clinicians.
In addition to scientific pursuit and collaboration, Nakshatri said a big motivation for his interest in breast cancer research is his work with organizations such as the Catherine Peachey Fund, which has provided him with the opportunity to meet breast cancer patients and hear their stories.
“The chance to interact with real patients who suffer from breast cancer is another driving force for me,” Nakshatri said.
Current research interests and discoveries
Nakshatri’s more recent work focuses on a variety of topics including gene mutations, breast cancer in men and breast cancer in women of African ancestry.
Nakshatri’s research group has observed a mutation in the gene PIK3CA found in not only around 40% of breast cancers but in normal breast tissue as well. Some other mutation must be occurring for cells to become cancerous, which his research team has now identified. The model work found that the resulting tumor is ductal carcinoma in situ (DCIS), a form of breast cancer that develops in the milk ducts of the breast, which was the first model the team has been able to build for DCIS, allowing for further research.
His research group has found that the signaling pathway for breast cancer in men differs from breast cancer in women. He’s worked on models of donated male healthy breast tissue to learn how cells become cancerous in male breast cancer compared to female breast cancer.
Research has shown that women of African ancestry tend to experience the worst outcomes of breast cancer compared with other populations, especially in women who hail from sub-Saharan Africa. These women carry a mutation in the gene known as ACKR1, which protects against malarial infection. But if they do develop breast cancer, it tends to be more aggressive, with Nakshatri’s team working to find out why.
Nakshatri said he is particularly interested in how breast cancer spreads. Breast cancer itself can be surgically removed and treated, but its spread can make treatment more complicated and often leads to worse health outcomes. If he or other researchers are able to discover the processes behind its spread, it could lead to better outcomes for patients everywhere.
