Eric H. Holbrook, M.D.
Assistant Professor of Otology and Laryngology, Harvard Medical School
The overall goal of our research is to understand the pathophysiology of olfactory disorders in humans and attempt to alter mechanisms of olfactory neurogenesis that have been identified in rodents. Models of olfactory epithelial damage using methyl bromide gas exposure and olfactory nerve transection in mice allow us to observe the regeneration of olfactory neurons. Exposure of olfactory receptors located on the cilia of these neurons to specific odors allow for enhanced survival and axonal targeting to the olfactory bulb during development, however it is unclear if this activity dependent survival and targeting occurs during regeneration after lesioning. Using naris occlusion and odorant exposure after insult to the olfactory system, we are looking at the effects of odorant induced neuronal activity on the selective enhancement in numbers and targeting of specific olfactory neurons. In addition to animal studies, we are looking at the overall distribution of olfactory mucosa in human autopsy specimens. In conjunction with Dr. James Schwob at Tufts University School of Medicine, immunohistochemical analysis and molecular analysis of this tissue are being performed to compare with what is already known in the rodent system. Changes in immunohistochemical as well as molecular expression of the stem and neuronal progenitor cells in patients with known olfactory disorders will be compared to expression patterns in rodent undergoing regeneration of olfactory epithelium in response to epithelial lesioning. In this way, we are translating the abundance of information known about the olfactory system in lower mammals to the human system in attempts to identify the pathophysiology behind the most common forms of olfactory loss: upper respiratory tract infection, head trauma, aging, and chronic rhinosinusitis.
Human olfactory mucosa stained with anti-PGP9.5 (red) and anti-OMP (green) directed antibodies. 40X
1. Holbrook EH, Mieleszko Szumowski KE, Schwob JE. An immunochemical, ultrastructural, and developmental characterization of the horizontal basal cells of rat olfactory epithelium. J Comp Neurol 1995;363:129-46.
2. Christensen MD, Holbrook EH, Costanzo RM, Schwob JE. Rhinotopy is disrupted during the reinnervation of olfactory bulb that follows transection of the olfactory nerve. Chem Senses 2001;26:359-69.
3. Holbrook EH, DiNardo LJ, Costanzo RM 2001 Olfactory epithelium grafts in the cerebral cortex: an immunohistochemical analysis. Laryngoscope 2001;111:1964-69.
4. Holbrook EH, Leopold DA, Schwob JE. Abnormalities of axon growth in human olfactory mucosa. Laryngoscope 2005; 115:2144-54.
5. Leopold DA and Holbrook EH. Physiology of olfaction. In: Cummings C et al. Otolaryngology-head and neck surgery, 4th edition. 2005; St. Louis, Missouri: CV Mosby.
6. Holbrook EH and Leopold DA. An updated review of clinical olfaction. Curr Opin Otolaryngol Head Neck Surg 2006;14:23-28. (Selected for publication in 2008-2009 edition of The Home Study Course.)