A magazine for friends of the Warren Alpert Medical School of Brown University.

Made for These Times

A Look Inside the Jain Lab

Krüppel-like factors


Jain’s lab is known for discovering a family of Krüppel-like factors and their role in regulating two major physiologic systems, the immune system and the metabolic system. “That’s really important,” Jain says, “because your immune and metabolic systems are not only fundamental to life, but their dysfunction contributes to the vast majority of age-associated diseases that impact society today: cardiovascular, neurodegenerative diseases, and cancer.”

These transcription factors mostly live in the nucleus of the cell where they interact with DNA and turn on and off hundreds of genes to control cell functions in health and disease. Mammals have 18 KLFs, and Jain’s lab was the first to link the gene family KLF15 to control of metabolism and its expression in metabolic tissues like liver, fat, and muscle. “It’s highly expressed and enriched in those tissues,” he says. The other two factors, termed KLF2 and KLF4, appear at high levels in the blood vascular system. “That’s really interesting as a cardiologist. We’ve been able to study their roles in a broad spectrum of vascular disease states like atherosclerosis, aneurysm formation, and heart failure,” he says.

There’s evidence that mutations in these factors can affect disease, and there are even medicines used clinically that have at least part of their action through these factors. “It’s very gratifying,” Jain says. “We’ve focused in our own laboratory on the immune system and the metabolic system, but there are hundreds of labs across the world that have or are studying these factors in many other processes, which is really exciting. We can’t do everything.”

“The immune and metabolic systems are quite central to many biological processes so I think we could collaborate with many colleagues in the Division of Biology and Medicine,” Jain adds. “The Center on the Biology of Aging is one possibility. I also have a grant on immune system and dementia and so there’s a connection to brain health and the Carney Institute [for Brain Science]. And then of course the cardiovascular researchers. There are a lot of connections.”

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