Jorge Henao-Mejia Explores the Immune System’s Controls
Jorge Henao-Mejia Explores the Immune System’s Controls

Jorge Henao-Mejia Explores the Immune System’s Controls

By tying together his understanding of the microbiome and nucleic acids, the UPenn immunologist is decoding the underlying causes of inflammation and disease.

Jan 1, 2019
Sukanya Charuchandra

ABOVE: © Colin Lenton

In 2005, Colombia native Jorge Henao-Mejia left what might have been a promising career in medicine to come to the US to explore the fundamental biology of the immune system. “Very few people get a chance to come to work every day just to pursue your own curiosity,” says Henao-Mejia, who now spends his days at the University of Pennsylvania dissecting the roles of long, noncoding RNA and gut microbiota in driving inflammation and disease.

His interest in basic science started as a medical student at the University of Antioquia in Medellín, where he had done some research on HIV. But resources were limited in the basic biology labs at the university, so Henao-Mejia looked for researchers to work with in the US. He ended up in the lab of Johnny He at Indiana University School of Medicine, where he studied the immune response to viruses, mainly HIV and hepatitis C.

After wrapping up his doctoral studies in 2009, Henao-Mejia landed a postdoctoral position in Richard Flavell’s immunology lab at Yale University School of Medicine. In his first major project, Henao-Mejia and colleagues found that gut microbiota can drive the development of nonalcoholic fatty liver disease.1 The takeaway from that study is that changes to the composition of the gut microbiome influence the movement of microbial products in the body through circulation, which in turn can affect the progression of nonalcoholic fatty liver disease, Henao-Mejia says.

Henao-Mejia also investigated a noncoding RNA, called miR-181, which turned out to be involved in the development of certain immune cells.2 Some of these RNA molecules are critical to regulate key immune cells “at play in many inflammatory diseases,” he says.

Henao-Mejia is “able to bring the best out of everybody,” Flavell says. He’s approachable and open to collaboration. “I think that reinforced what was really developing in the lab at the time, which was that in order to be successful in this era [when] science is so multidisciplinary, you have to work together,” Flavell says.

Henao-Mejia started his own lab at the University of Pennsylvania in 2014. “When we interviewed him, it was very clear that he was one of these people that just catalyzed science around him,” says E. John Wherry, an immunologist at the University of Pennsylvania who helped recruit Henao-Mejia.

At UPenn, Henao-Mejia continues to explore RNA. Recently, his group found that a gene called Morrbid encodes a long noncoding RNA that closely controls the survival of short-lived myeloid white blood cells, such as monocytes and neutrophils, to unleash and curb inflammation.3 His team also determined the regulatory function of a long noncoding RNA in the development of a specific class of lymphoid helper and natural killer (NK) cells.4 These papers showed that extracellular cues such as cytokines could alter noncoding RNA levels to fine-tune or disrupt the immune response.

Henao-Mejia says he feels lucky to have the freedom to search for answers to questions that intrigue him. “There are very significant technological advancements that now allow us to ask much more refined questions to understand how biological systems work.”

References

  1. J. Henao-Mejia et al., “Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity,” Nature, 482:179–85, 2012. (Cited 1381 times)
  2. J. Henao-Mejia et al., “The microRNA miR-181 is a critical cellular metabolic rheostat essential for NKT cell ontogenesis and lymphocyte development and homeostasis,” Immunity, 38:984–87, 2013. (Cited 163 times)
  3. J.J. Kotzin et al., “The long non-coding RNA Morrbid regulates Bim and short-lived myeloid cell lifespan,” Nature, 537:239–43, 2016. (Cited 59 times)
  4. W.K. Mowel et al., “Group 1 innate lymphoid cell lineage identity is determined by a cis-regulatory element marked by a long non-coding RNA,” Immunity, 47:435–49.e8, 2017. (Cited 16 times)