Just a few months after his laboratory was named in honor of prominent local benefactor Joseph A. Negri, Professor of Microbiology and Immunology Dr. Roman Dziarski and his wife, Dr. Dipika Gupta , assistant professor of biochemistry and molecular biology, are showing just why IUSM-Northwest is the right institution to carry out Negri's intended legacy of HIV/AIDS research in Northwest Indiana.      

Published in the July 28 issue of the Journal of Biological Chemistry , the latest study from Dziarski and Gupta's ongoing research into bacteria-battling human proteins reported that these proteins, called PGLYRP – peptidoglycan recognition proteins -- are produced in varying amounts by different organs in the human body. The skin, for example, produces these proteins only when exposed to virulent or high numbers of bacteria, whereas the liver produces PGLYRP constantly.

The researchers believe this difference may relate to the various functions of different organs. Because the liver's job is to monitor the blood and fight acute infection, its constant production of PGLYRPs may help it fulfill this preventative role as a blood filter.    

Gupta and Dziarski first announced their discovery of this previously unknown class of antibacterial proteins in research published in the same journal last winter. The proteins are believed to be the body's first wave of defense against disease-causing bacteria, as they are deployed well before the body's primary immune system goes into action.

This discovery may offer hope to patients, such as those with HIV/AIDS, who suffer from impaired immune systems and are therefore susceptible to infections and diseases that healthy people fight off with relative ease. The IUSM-Northwest researchers believe that greater understanding of how these proteins interact with and defeat bacteria could lead to medications that would boost the immune response of such patients.

“We believe that these proteins open up a whole new area of research on so-called ‘innate immunity,' the ability of cells and tissues to fight off infection without the help of immune cells,” Dziarski said in March. “In fact, future research on how to stimulate cells to over-produce these proteins or ways to use them as medicines may help in treating patients with compromised immune systems like those seen in HIV/AIDS cases.”

This research helps to advance the mission that Negri assigned to IUSM-Northwest when he bestowed funds from his estate to the medical school for the purpose of advancing research into HIV/AIDS and related diseases. On May 15 of this year, IUSM-Northwest officials dedicated the Joseph A. Negri Laboratory for HIV/AIDS and related research.

“This will ensure, true to the wishes of Mr. Negri, that HIV/AIDS-related research will always be a part of our medical school branch's mission in perpetuity,” said Dr. Patrick Bankston, director and assistant dean of IUSM-Northwest. “Some of the funds from the Negri estate have been used to purchase a state-of-the-art confocal computer-controlled fluorescent microscope to help with Dr. Dziarski's research.”

“We are happy for both the designation of our laboratory to the memory and cause of Mr. Negri and for the new equipment his donation has provided,” Dziarski said. “The new confocal scope is a powerhouse and the only one in Northwest Indiana . This will enable us to look at cells in an entirely different way that I am sure will lead to new discoveries.”

The latest studies from Dziarski, Gupta and their research team build on work that began five years ago, when they identified four new genes in the human genome by comparing a genome of a fruit fly, Drosophila melanogaster , to the human genome. Dziarski and Gupta cloned three of these genes, while a Swedish researcher cloned the fourth gene. These genes are called peptidoglycan recognition proteins because they produce proteins that degrade or bind to peptidoglycan, a molecule found on the outer surface of all bacteria.

One of the four genes codes for an enzyme, produced in the liver and secreted into the blood, that degrades peptidoglycan. The presence of bacteria in the skin or the intestines can also spur production of this enzyme, which may protect the body from damage or inflammation caused by bacteria. The other three genes produce proteins that bind to peptidoglycan.

Two of these genes, according to Gupta, are present in skin cells, sweat, saliva, eyes, the mouth, and throughout the intestinal tract. This affords them an optimal position from which to vanquish bacteria before the disease-causing agents can enter tissues. The final bacteria-hunting protein is produced by phagocytic cells, the main immune cells found in blood and tissues, she said.

Dziarski and Gupta have published the ongoing results of their studies in the Journal of Biological Chemistry , Blood and other esteemed publications. The next step, they said, is to determine the exact mechanisms that allow PGLYRPs to bind to peptidoglycan and kill bacteria.   

“We have to figure out exactly how the proteins kill bacteria,” Dziarski said. “We know they kill them, but we need to know exactly how. The next step after that is to see if we can use these proteins to fight infections in patients. That's a big step.”

In addition to their enthusiasm about the promising practical applications of their work, Dziarski and Gupta are pleased to have contributed to the overall body of knowledge about the human genome. And their work is a fine example of the kind of cutting-edge research that continues to unfold at IUSM-Northwest.

“We are very proud of these discoveries by Drs. Dziarski and Gupta and their collaborators,” Bankston said. “Dr. Dziarski's National Institute of Health-supported research has been very fruitful and could eventually lead to commercial production of important medicines. This work represents the kinds of discoveries we need more of in Northwest Indiana as part of any life-sciences or biotechnology economic development efforts here. Our medical school branch will devote itself to be the focus of such efforts.”

Negri's donation is also helping to fund the Northwest Indiana Health Research Institute (NWIHRI) at IUSM-Northwest. The mission of NWIHRI, which was inaugurated on May 15, is to foster basic bench, clinical and translational medical research. The NWIHRI is housed in the new Dunes Medical/Professional Building on the IU Northwest campus.   

“The Institute will be devoted to expanding that research with new scientists and new research directions, including clinical research involving our local physicians, local hospitals and local patients to get the best in care to all our patients,” said Amy Han, director of development at IUSM-Northwest. “The Negri Laboratory and the research institute represent IUSM-Northwest's initial efforts to contribute to life sciences and biotechnology economic development efforts in Northwest Indiana .”