Dr. Holbrook’s research looks at ways to understand the ability of the olfactory epithelium to regenerate after injury. His long-term goal is to integrate what is learned in the laboratory with his clinical understanding of olfactory loss to either prevent further progression or reverse the process of smell loss in humans. Previous research projects supported the finding of odorant evoked neuronal activity in the enhancement of survival and axonal targeting of receptor neurons after olfactory epithelial lesions in mice. This suggests a possible role for odorant therapy in the treatment of human olfactory disorders. A clinical study is being developed to test this therapy.

Further research has focused on the characterization of the olfactory mucosa in humans and a comparison with staining and molecular expression patterns identified in rodents. A description of reproducible staining patterns in various regenerative states can help propose mechanisms of pathology in human olfactory disorders that show comparable patterns in biopsy specimens. Dr. Holbrook has demonstrated that mouse and human epithelium are remarkably similar, and the human mucosa appears to retain regenerative capacity even in extreme ages. The olfactory area seems to decrease with age, but to a lesser degree than we anticipated.

Given the findings in human autopsy material, potentially the problems of smell loss related to aging may be a function of abnormalities with the bulb or brain instead of the epithelium. Abnormalities of central areas may also occur with other forms of human olfactory loss as a primary source or as a secondary outcome to long-term denervation. A permanent alteration of central areas may make efforts at repairing epithelial disorders ineffective for treating smell loss. To study the effects of long-term olfactory neuronal loss on both the epithelium and central areas we have developed a novel mouse model of an inducible and reversible lesion. The findings mirror some examples we see in human olfactory tissue.

In addition to research on the sense of smell, multiple clinical projects relating to outcomes in the treatment of sinus disease and the mechanisms of chronic sinusitis are currently ongoing. Many of these projects are in conjunction with other faculty at Mass. Eye and Ear, as well as specialists from Mass General in the allergy and neurosurgery fields.