S. Ananth Karumanchi, MD

2002 Carl W. Gottschalk Research Scholar Grant

Beating the Odds: A Researcher’s Creative Vision Realized

“ASN took a chance on me.”

From his earliest exposure to medicine, S. Ananth Karumanchi, MD was “fascinated by the way the kidney precisely filters out all the toxic material and maintains the electrolytes and acid-base status.”

After graduating from medical school in India, he came to the U.S. for a residency in internal medicine at Henry Ford Hospital in Detroit, drawn by the presence of Robert G. Narins, MD. During his nephrology fellowship at Beth Israel Deaconess Medical Center in Boston he began working in the lab of Vikas Sukhatame, MD. There Dr. Karumanchi focused on tumor angiogenesis, using microarray chips to identify individual proteins. This was a new technology, and exploring it, Dr. Karumanchi was drawn to the pregnancy complication of preeclampsia, where “the primary abnormality is in the vasculature. The kidneys and placenta have damaged blood vessels. And the mother has hypertension, which is a vascular disease.”

His chip studies uncovered a suspicious angiogenesis inhibitor—the protein soluble FLT present at high levels in the blood and placentas of women with preeclampsia. He accumulated evidence of its effects, including from an animal model: Rats given soluble FLT developed hypertension and proteinuria. “Pathologists who looked at sections of these rat kidneys would say they looked exactly like what you would see in a kidney biopsy from patients with preeclampsia,” Dr. Karumanchi noted.

Convinced he’d made a significant discovery that merited further investigation, Dr. Karumanchi faced obstacles common to young, unknown researchers, especially those breaking new ground: he could not get the attention of the scientific world: “It was very discouraging. I submitted numerous grant applications, but all were rejected. I was having a hard time getting the first paper published.”

His fortunes changed when he received an ASN Career Development Grant in 2002: “ASN took a chance on me. Grant funding at an early stage allowed me to explore this discovery. If I hadn’t received it, I may have quit and pursued something else.”

Dr. Karumanchi broke through barriers with several papers which helped convince NIH to begin funding his research. Some 15 years later, with the significance of his early work validated by a host of other researchers, diagnostic tests based on soluble FLT are available. He is working with Dr. Ravi Thadhani, chief of nephrology at the Massachusetts General Hospital, to test strategies to lower soluble FLT levels in preeclamptic women.

“I was at the right place at the right time asking the right questions. Many people had tried to solve this problem, but I had access to new technology. ASN’s Career Development Grant really built my career, and I think that is the point—we have to fund young people. When you are young you tend to take chances. You ask new questions, and sometimes you luck out and find something big,” Dr. Karumanchi said.

Dr. Karumanchi is currently a Professor of Medicine at Beth Israel Deaconess Medical Center of Harvard Medical School in Boston, MA.