Immunotoxicology Laboratory - Dr. Jared Brown

Research in the Brown lab broadly focuses on immune responses to environmental and occupational exposures. Our research ranges from understanding immune responses to nanoparticles and air pollution to chemical warfare agents and occupational exposures. In addition, we are interested in developing novel nanotherapeutics for treatment of cancer and allergic disease. Examples of current projects in the Brown lab are described below:

1. Understanding mechanisms of non-IgE mast cell activation by environmental particulates.

This work, funded by NIEHS R01 ES019311, is examining novel mechanisms by which nanoparticles and airborne particulate matter trigger non-IgE mast cell activation contributing to adverse pulmonary and cardiovascular outcomes. Specifically, we are investigating redox and non-redox mechanisms linked with thioredoxin interacting protein and its potential regulatory role in mast cell degranulation. In addition, we are interested in cellular metabolism changes which occur between IgE and non-IgE mast cell degranulation that may provide insight into disease mechanisms in mast cell activation disorders. Lastly, we are working with Drs. Stephen Dreskin and Jenny Stitt from the Anschutz School of Medicine to examine these mechanisms of non-IgE mast cell degranulation in patients with chronic idiopathic urticaria.

2. Silica Nephropathy and Chronic Kidney Disease of Unknown Etiology.

This work, funded by NIDDK R01 DK12351 and in collaboration with Drs. Richard Johnson and Carlos Roncal within the School of Medicine, is examining the contribution of inhaled silica nanoparticles produced during burning of sugarcane fields in the development of chronic kidney disease of unknown etiology (CKDu). CKDu is worldwide epidemic largely associated with coastal agricultural workers leading to chronic kidney disease in young individuals and often resulting in kidney transplant or death. There are many potential contributing factors including heat stress, dehydration and environmental exposures. We are currently examining kidney biopsy sections from CKDu patients for the presence of silica nanoparticles that are found in high abundance in the ash from sugarcane burning. We are using two novel techniques to identify silica nanoparticles in biopsy sections: 1) single particle inductively coupled plasma mass spectrometry to provide size and chemical information on the silica nanoparticles and 2) enhanced darkfield hyperspectral imaging to image nanoparticles in tissue. In addition, we are using a human proximal convoluted tubule cells and animal models to investigate potential mechanisms of toxicity by sugarcane ash and purified amorphous silica nanoparticles.

3. Contribution of mast cells to nitrogen mustard pulmonary and central nervous system toxicity.

This work, funded by the NIEHS and the Department of Defense and working with Dr. Neera Tewari-Singh (Michigan State University), is investigating the role of mast cells in mediating inflammation in response to exposure to sulphur mustard and phosgene oxime, both of which are chemical warfare agents. We have utilized a mouse model of mast cell deficiency to demonstrate that in the absence of mast cells that inflammation resulting from sulphur mustard exposure is largely diminished. In addition, we are examining the effects of mast cell activation in the brain following sulphur mustard exposure. Lastly, we developing a nanoparticle based therapeutic to prevent mast cell activation as a prophylactic treatment for military personnel and civilians to prevent the effects of chemical warfare agents.

4. Inductively coupled plasma mass spectrometry studies:

Our lab employs ICP-MS to investigate environmental metal exposures across human, animal, and cellular samples. Through several funded collaborations with multiple investigators, we analyze trace metal concentrations to assess exposure risks and biological impacts. Utilizing our NexION 2000 ICP Mass Spectrometer, we have developed a distinct single particle method to both measure nanoparticles and identify individual metals.