Research Personnel: Bridget Wicinski, Jessie Laffey
Summary of Research Studies: Our research is directed towards the study of selective neuronal vulnerability in dementing illnesses using classical neuropathological as well as modern quantitative immunohistochemical methods. We intend to develop a quantitative, detailed and cohesive definition of neuronal susceptibility to degeneration in the cerebral cortex, by extending data on Alzheimer disease to other dementing disorders as well as animal models of age-related illnesses, and by defining the key neurochemical and morphological characteristics linked to relative vulnerability (or resistance to degeneration) of identified neuronal populations. The regional and laminar distribution in the cerebral cortex of specific neuronal populations is investigated in a variety of neurodegenerative disorders, and quantitatively compared to Alzheimer disease and control brains. In addition, a detailed study of brains from aged patients with no records of neurological and psychiatric disorders is performed in order to define further the limits of normal aging in the brain.
We employ advanced microscopy, high field magnetic resonance imaging, stereologic, and modeling approaches to develop an accurate quantitative assessment of such pathological changes in a region- and layer-specific manner. Neuronal morphology is analyzed morphometrically using intracellular injection of hippocampal and neocortical neurons coupled with computerized reconstruction to assess the degree to which the accumulation of pathologic markers causes dendritic atrophy and spine loss in different subtypes of neocortical pyramidal cells subserving cortical circuits critical for memory and cognition. The characterization of such vulnerable neurons and circuits is fundamental to the design of therapeutic strategies aiming at their protection or rescue. Similar approaches are applied to the neuropathology of schizophrenia and autism. We are also participating in a large-scale project with the Brain Initiative Cell Census Network to develop an integrated quantitative atlas of cortical cell types registered to high-resolution imaging datasets, using multiplexing and large-specimen light-sheet imaging approaches.
Finally we are investigating mammalian brain evolution with a focus on cetaceans and great apes. These studies have led us to identify specific neuronal types in parts of the cerebral cortex known to be involved in social awareness, judgment, and attention that can be considered as markers of adaptive mechanisms and functions in response to particular ecological pressure.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device, biotechnology companies, and other outside entities to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their outside financial relationships.
Dr. Hof has not yet completed reporting of Industry relationships.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device, biotechnology companies, and other outside entities to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their outside financial relationships.
Dr. Hof has not yet completed reporting of Industry relationships.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.
