When Jack Harkema, DVM, PhD, DACVP, ATSF, started veterinary school at Michigan State University, his plans were straight forward. He was going to be a large animal veterinarian after graduation.
But then, in his last year of school, he did an externship at the Lovelace Respiratory Research Institute in Albuquerque, New Mexico, where he studied the effects of air pollution on the respiratory system. The trajectory of his career took a sharp turn up into the atmosphere.
Today, the University Distinguished Professor, who holds the Albert C. and Lois E. Dehn Endowed Chair in Veterinary Medicine for the Department of Pathobiology and Diagnostic Investigation, serves as the director of the MSU Laboratory for Environmental and Toxicology Pathology and the MSU Mobile Air Research Laboratories (AirCARE 1 and 2). He also is known around the world for his research on the cellular and molecular mechanisms behind airway injury caused by air pollutants in both animals and humans.
After he earned his DVM, Harkema worked as a clinician scientist at Lovelace for two years, before leaving for a doctoral program and pathology residency at the University of California-Davis. After his residency/graduate training, he was rehired by Lovelace as a staff pathologist, thinking he would likely stay there for the rest of his professional career. But after nine years, MSU recruited him to East Lansing, where he accepted a faculty position in the Department of Pathology.
“My research has evolved over the years, but I’ve always been investigating the health effects of air pollutants on both animals and people,” he says. “It’s very relevant to the One Health concept, which involves looking at the connections between health -- in both humans and animals -- and the environment. My research today has the same basic framework as it did when I started my career in Albuquerque and Davis, though the methods and materials of investigation have changed dramatically.”
Harkema is involved in a number of research projects including working with an interdisciplinary team of researchers at MSU and the University of New Mexico to use the AirCARE1 Mobile Air Research Laboratory to examine health problems caused by exposure to metal-rich particulate matter from abandoned uranium mine sites located on the Navajo Nation in Arizona and New Mexico.
In another project that may have broad implications for human health, Harkema is investigating the link between breathing crystalline silica, or quartz dust, and the triggering of lupus, an autoimmune disease that is estimated to affect 1.5 million people in the United States and at least 5 million people worldwide. Lupus manifests as inflammation in multiple organs including the kidneys and lungs. Repeated inflammatory episodes (flares) caused by environmental triggers, such as breathing silica dust, can lead to not only pulmonary inflammation, but also chronic renal failure and eventually, the need for a kidney transplant.
“In autoimmune diseases like lupus, the immune system goes haywire and produces autoantibodies that attack the body,” Harkema says. “If we can prevent that response, we can extend lives. There are very few drugs that effectively treat or prevent lupus flares and, in most cases, each drug only targets one facet of this complicated and devastating disease.”
Harkema works with mice that are genetically prone to lupus, and the disease is similar in its manifestations in both mice and people. The animals are exposed to the silica dust and then develop the disease many weeks earlier than normal.
“Our mice are models for occupational exposure,” he explains. “People in mining and construction, as well as people in the military exposed to dust storms in sandy desert environments, have a higher rate of lupus than the general population. It is believed that breathing silica dust damages the lungs, which triggers an autoimmune response in people who are genetically prone to develop lupus. Besides lupus, silica exposure may trigger other autoimmune diseases, such as rheumatoid arthritis.”
In collaboration with Jim Pestka, University Distinguished Professor and Robert and Carol Deibel Family Endowed Professor for the Department of Food Science and Human Nutrition, Harkema is studying whether docosahexaenoic acid, commonly known as DHA, a polyunsaturated omega-3 fatty acid, can offset the symptoms of lupus and, potentially, other autoimmune diseases.
“We’re looking at whether DHA supplementation can be used to prevent or treat lupus,” Harkema explains. “Our experimental protocol is to expose the genetically-prone mice to silica dust and give them DHA in their diet at doses relevant to human supplementation, either before or after the silica exposure. Because women are more prone to lupus than men, all the mice in our study are females. What we’ve found is that more than 90 percent of the lung and kidney lesions are prevented with DHA. It’s a very striking effect. The DHA doesn’t prevent all the lung damage caused by the inhaled silica, but it does effectively stop the autoimmune response in the lung and throughout the body including the kidneys.”
Pestka, Harkema, and their other colleagues at MSU and elsewhere have recently received a five-year grant from the National Institutes of Health to further investigate the cellular and molecular mechanisms by which DHA prevents silica-triggered lupus flares in mice.
“Based on the encouraging results from our initial preclinical studies, we are excited about the clinical prospects for DHA supplementation as a treatment or prevention for lupus,” Harkema says. “I have focused for many years on identifying toxic agents in air pollution and their impact on human health. It is now exciting for me to be part of a talented team of investigators and students discovering interventions that may effectively prevent the onset and exacerbation of a common autoimmune disease that can be triggered by an airborne toxicant.”