Jack Harkema, DVM PhD DACVP ATSF

University Distinguished Professor
Pathobiology & Diagnostic Investigation, Pharmacology & Toxicology

Bio

I am a board-certified veterinary pathologist with extensive experience in pulmonary pathology of laboratory animals. I have been an academic biomedical researcher and mentor of graduate/medical/veterinary students, pathology residents, and postdoctoral fellows for over 30 years in the areas of respiratory toxicology and pathology. My personal research focuses on the elucidation of biological mechanisms underlying airway epithelial cell injury, repair, and disrepair to xenobiotics (e.g., air pollutants, allergens, viruses, microbial toxins). Much of my recent research has focused on developing animal models of human respiratory, cardiovascular, metabolic, and autoimmune diseases (e.g., asthma, metabolic syndrome, systemic lupus erythematosus) used to investigate how pre-existing disease may affect an individual’s susceptibility to air pollutants (e.g., particulate matter, ozone). My career has been fostered by a network of extensive and highly productive collaborations reflected in over 290 publications with coauthors from 20+ units at Michigan State University (MSU) and more than 100 national and international laboratories. More recent collaborative activities with others at MSU and elsewhere are based on my experience with animal studies designed to better understand the pathogenesis of pulmonary diseases caused by inhaled toxic agents, e.g., air pollutants, as well as interventions to prevent/treat environmental triggers of chronic human diseases, such as diabetes, lupus, and asthma.

Colleges

• College of Veterinary Medicine

Associations

• Director, Laboratory for Environmental and Toxicologic Pathology

Programs

• Environmental & Integrative Toxicological Sciences Training Program

Education

• Ph.D., Pathology (School of Veterinary Medicine), University of California, Davis ()
• Postdoctoral Fellow, Inhalation Toxicology, Lovelace Respiratory Research Institute ()
• D.V.M., Veterinary Medicine, Michigan State University ()
• M.S., Physiology, Michigan State University ()
• B.S., Biology, Calvin University ()

Funding

• Genetic Analysis of COVID-19 Susceptibility and Resistance Determinants in the Collaborative Cross, National Institute of Allergy and Infectious Diseases (2022—2023)
• Dietary Lipids and Silica-Triggered Autoimmunity, National Institute of Environmental Health Sciences (2017—2023)
• Role of alveolar macrophage in omega-3 fatty acid amelioration of silica-triggered autoimmunity, National Institute of Environmental Health Sciences (2023—2027)
• Toxic lipid intermediate accumulation and cobalamin depletion promote AHR-mediated hepatotoxicity and the progression of non-alcoholic fatty liver disease (NAFLD)-like pathologies, National Institute of Environmental Health Sciences (2022—2027)
• Gene-Environment Interactions with Ozone and Non-atopic Asthma, National Institute of Environmental Health Sciences (2021—2023)
• Impact of Particle and Ozone Inhalation Co-Exposure on Alveolar Epithelial Regeneration, National Institute of Environmental Health Sciences ()
• Computational Modeling of Aerosol Dosimetry in the Ferret Respiratory Tract, Cystic Fibrosis Foundation (2021—2024)

Works

• Lipidome modulation by dietary omega-3 polyunsaturated fatty acid supplementation or selective soluble epoxide hydrolase inhibition suppresses rough LPS-accelerated glomerulonephritis in lupus-prone mice. Frontiers in immunology (2023)
• Aerosol physicochemical determinants of carbon black and ozone inhalation co-exposure induced pulmonary toxicity. Toxicological sciences : an official journal of the Society of Toxicology (2023)
• Prevention of bleomycin-induced lung fibrosis via inhibition of the MRTF/SRF transcription pathway. Pharmacology research & perspectives (2022)
• A Locus on Chromosome 15 Contributes to Acute Ozone-induced Lung Injury in Collaborative Cross Mice. American journal of respiratory cell and molecular biology (2022)
• Science-based Policy Recommendations for Fine Particulate Matter in the United States. American journal of respiratory and critical care medicine (2022)
• Single cell analysis of docosahexaenoic acid suppression of sequential LPS-induced proinflammatory and interferon-regulated gene expression in the macrophage. Frontiers in immunology (2022)
• Comparative effects of human-equivalent low, moderate, and high dose oral prednisone intake on autoimmunity and glucocorticoid-related toxicity in a murine model of environmental-triggered lupus. Frontiers in immunology (2022)
• Inflammation as a Key Outcome Pathway in Particle Induced Effects in the Lung. Frontiers in public health (2022)
• Neuroinflammatory and Neurometabolomic Consequences From Inhaled Wildfire Smoke-Derived Particulate Matter in the Western United States. Toxicological sciences : an official journal of the Society of Toxicology (2022)
• In Vitro and In Vivo Analysis of Extracellular Vesicle-Mediated Metastasis Using a Bright, Red-Shifted Bioluminescent Reporter Protein. Advanced genetics (Hoboken, N.J.) (2022)
• Silica Induction of Diverse Inflammatory Proteome in Lungs of Lupus-Prone Mice Quelled by Dietary Docosahexaenoic Acid Supplementation. Frontiers in immunology (2022)
• A Murine Model of Ozone-induced Nonatopic Asthma from the Collaborative Cross. American journal of respiratory cell and molecular biology (2021)
• Combined adjuvant effects of ambient vapor-phase organic components and particulate matter potently promote allergic sensitization and Th2-skewing cytokine and chemokine milieux in mice: The importance of mechanistic multi-pollutant research. Toxicology letters (2021)
• Hyperspectral microscopy of subcutaneously released silver nanoparticles reveals sex differences in drug distribution. Micron (Oxford, England : 1993) (2021)
• Transcriptomics of single dose and repeated carbon black and ozone inhalation co-exposure highlight progressive pulmonary mitochondrial dysfunction. Particle and fibre toxicology (2021)
• Prevention of Drug-Induced Lung Fibrosis via Inhibition of the MRTF/SRF Transcription Pathway. (2021)
• Oxidant-induced epithelial alarmin pathway mediates lung inflammation and functional decline following ultrafine carbon and ozone inhalation co-exposure. Redox biology (2021)
• In vitro and in vivo analysis of microvesicle-mediated metastasis using a bright, red-shifted bioluminescent reporter protein of extracellular vesicles. (2021)
• Neuroinflammatory and neurometabolic consequences from inhaled 2020 California wildfire smoke-derived particulate matter at a remote location. (2021)
• Fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, blocks steatosis and alters the inflammatory response in a mouse model of inflammation-dioxin interaction. Chemico-biological interactions (2021)
• Omega-3 Polyunsaturated Fatty Acid Intervention Against Established Autoimmunity in a Murine Model of Toxicant-Triggered Lupus. Frontiers in immunology (2021)
• Establishing a university food pantry: growth, changes in shopper characteristics and recommendations. Journal of American college health : J of ACH (2021)
• Respiratory and systemic impacts following MWCNT inhalation in B6C3F1/N mice. Particle and fibre toxicology (2021)
• The clear and persistent impact of air pollution on chronic respiratory diseases: a call for interventions. The European respiratory journal (2021)
• Rapid Induction of Pulmonary Inflammation, Autoimmune Gene Expression, and Ectopic Lymphoid Neogenesis Following Acute Silica Exposure in Lupus-Prone Mice. Frontiers in immunology (2021)
• Repetitive Ozone Exposures and Evaluation of Pulmonary Inflammation and Remodeling in Diabetic Mouse Strains. Environmental health perspectives (2020)
• Assessment of particulate matter toxicity and physicochemistry at the Claim 28 uranium mine site in Blue Gap, AZ. Journal of toxicology and environmental health. Part A (2020)
• Omega-3 fatty acid intake suppresses induction of diverse autoantibody repertoire by crystalline silica in lupus-prone mice. Autoimmunity (2020)
• Pathogenesis and Persistence of Increased Epithelial Mucosubstances in the Nasal Airways of Rats and Mice Episodically Exposed to Ethylene. Toxicologic pathology (2020)
• Requisite Omega-3 HUFA Biomarker Thresholds for Preventing Murine Lupus Flaring. Frontiers in immunology (2020)
• Serum-borne factors alter cerebrovascular endothelial microRNA expression following particulate matter exposure near an abandoned uranium mine on the Navajo Nation. Particle and fibre toxicology (2020)
• The Need for a Tighter Particulate-Matter Air-Quality Standard. The New England journal of medicine (2020)
• Airborne particulate matter from goat farm increases acute allergic airway responses in mice. Inhalation toxicology (2020)
• Influence of total western diet on docosahexaenoic acid suppression of silica-triggered lupus flaring in NZBWF1 mice. PloS one (2020)
• Livestock farm particulate matter enhances airway inflammation in mice with or without allergic airway disease. The World Allergy Organization journal (2020)
• MyD88 regulates a prolonged adaptation response to environmental dust exposure-induced lung disease. Respiratory research (2020)
• Outdoor Air Pollution and New-Onset Airway Disease. An Official American Thoracic Society Workshop Report. Annals of the American Thoracic Society (2020)
• Arsenic and benzo[a]pyrene co-exposure acts synergistically in inducing cancer stem cell-like property and tumorigenesis by epigenetically down-regulating SOCS3 expression. Environment international (2020)
• Chronic, Elevated Maternal Corticosterone During Pregnancy in the Mouse Increases Allergic Airway Inflammation in Offspring. Frontiers in immunology (2020)
• Transcriptional Profiling of the Murine Airway Response to Acute Ozone Exposure. Toxicological sciences : an official journal of the Society of Toxicology (2020)
• Docosahexaenoic Acid Consumption Impedes Early Interferon- and Chemokine-Related Gene Expression While Suppressing Silica-Triggered Flaring of Murine Lupus. Frontiers in immunology (2019)
• Influx, Persistence, and Recall of Eosinophils and GATA-3+ Innate Lymphoid Cells in the Nasal Mucosa of Mice Exposed and Reexposed to the Gaseous Air Pollutant Ozone. Toxicologic pathology (2019)
• Lupus, Silica, and Dietary Omega-3 Fatty Acid Interventions. Toxicologic pathology (2019)
• Role of chemical composition and redox modification of poorly soluble nanomaterials on their ability to enhance allergic airway sensitisation in mice. Particle and fibre toxicology (2019)
• Innate Lymphoid Cell-Dependent Airway Epithelial and Inflammatory Responses to Inhaled Ozone: A New Paradigm in Pathogenesis. Toxicologic pathology (2019)
• Correction: Silica-Triggered Autoimmunity in Lupus-Prone Mice Blocked by Docosahexaenoic Acid Consumption. PloS one (2019)
• Docosahexaenoic Acid (DHA) Suppresses Broad Spectrum of Pathogenic Autoantibodies Elicited in Murine Model of Lupus Flaring (OR12-03-19). Current developments in nutrition (2019)
• Transcriptional profiling of the murine airway response to acute ozone exposure. (2019)
• Mapping of Dynamic Transcriptome Changes Associated With Silica-Triggered Autoimmune Pathogenesis in the Lupus-Prone NZBWF1 Mouse. Frontiers in immunology (2019)
• Neighborhood air pollution and household environmental health as it relates to respiratory health and healthcare utilization among elderly persons with asthma. The Journal of asthma : official journal of the Association for the Care of Asthma (2019)

Employment

• University Distinguished Professor, Michigan State University (2019-05-01)
• University Distinguished Professor, Michigan State University (1994-08-01)
• Senior Staff Scientist/Pathologist, Lovelace Respiratory Research Institute (1985-11-01—1995-07-15)