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Uncovering How Hemeprotein Maturation, Regulation Contributes to Disease

09/09/2019

Dennis Stuehr, PhD, Department of Inflammation & Immunity, was recently awarded a four-year, $1.9 million grant from the National Institute of General Medical Sciences, part of the National Institutes of Health, to investigate how hemeproteins contribute to a host of biological processes critical for life, and may be associated with a broad number of clinically relevant diseases, including asthma, autoimmune disorders, bacterial infections and more.

Hemeproteins are a class of proteins that, as the name implies, contain a heme group—the iron-containing element in blood. Scientists have long known that they are important to a range of processes throughout the body, including opening blood vessels and lung airways, storing oxygen in tissues and fighting off bacterial infections. The details behind hemeprotein maturation and regulation, however, are not currently understood as well.

In a paper published last year, Dr. Stuehr and collaborators described for the first time how hemoglobin—a hemeprotein that transports oxygen to cells throughout the body—forms and matures. His team showed that a chaperone protein called hsp90 (heat shock protein 90) is critical for selective protein binding and is the key to forming functional, mature hemoglobin.

This award will enable Dr. Stuehr to continue this line of investigation into three other hemeproteins, including soluble guanylate cyclase, myoglobin and nitric oxide synthase.

The researchers will study these proteins both in their purified forms and inside living cells to understand the cellular events that create their mature and active forms, as well as the events that lead to their damage. Understanding of these events will help researchers identify therapeutic targets that can promote, preserve or recover hemeprotein functions that may protect against a broad range of diseases, including asthma, cardiovascular blockage, autoimmune disorders and bacterial infections.

Dr. Stuehr is the recipient of the 2018 Edward W. Morely Medal presented by the American Chemical Society Cleveland Section. The award recognized Dr. Stuehr for his significant contributions to the field of chemistry, including his seminal discovery of nitric oxide synthase.



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