Patrick R. Hof
- PROFESSOR Neuroscience
- PROFESSOR Geriatrics and Palliative Medicine
- PROFESSOR Ophthalmology
- Alzheimer's Disease
- Brain Imaging
- Cerebral Cortex
- Comparative Anatomy
- Glutamate (NMDA & AMPA) Receptors
- Magnetic Resonance Imaging
- Mental Retardation
- Neural Networks
- Prefrontal Cortex
- Quantitative Neuroanatomy
The Scripps Research Institute
M.D., University of Geneva School of Medicine
- Dr. Hof is the Regenstreif Professor of Neuroscience and Vice-Chair for the Department of Neuroscience. In the Department, Dr. Hof also leads the Kastor Neurobiology of Aging Laboratories. His laboratory has extensive expertise in the pathology of neuropsychiatric disorders and has established an international reputation in quantitative approaches to neuroanatomy and studies of brain evolution.
* Department of Neuroscience
* Computational Neurobiology and Imaging Center
* Laboratory of Neuromorphology
ResearchSpecific Clinical/Research Interest:
Experimental neuropathology, neurodegenerative disorders, brain aging; Functional anatomy of the cerebral cortex, comparative neuroanatomy; Computer-assisted morphometry, stereology, microscopy; Magnetic resonance microscopy, functional brain imaging
Current Students: Hannah Brautigam, PhD, Danae Papapetrou, PhD, Neha Uppal, PhD, Patrick Coskren, PhD, Xiaosi Gu, PhD
Postdoctoral Fellows: Camilla Butti, PhD, Micaela Santos, MD, Aniruddha Yadav, PhD, Malin Hoistad, PhD
Research personnel: Bridget Wicinski, Yasmeen Afzal, Alfredo Rodriguez, Emily Eaves, Tony Gao
Summary of Research Studies:
Our research is directed towards the study of selective neuronalvulnerability 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 also investigate transgenic mouse models, expressing the human tau gene or mutations in the amyloid precursor protein. We study spatial and temporal relationships between neuronal integrity and reflections of degeneration such as tangle formation, amyloid deposition and microvascular damage. We employ high field magnetic resonance microscopy, stereologic, and mathematical modeling approaches to develop an accurate quantitative appraisal of such pathological changes in a region- and layer-specific manner. Neuronal morphology is assessed in a quantitative manner 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.
Such correlations of quantitative anatomical analyses and clinical data will be valuable to determine the causes and mechanisms of dementia and aging-related pathologies of the central nervous system. Altogether our research efforts will provide a quantitative assessment, in dementia cases of different severity and in relevant animal models, of the relative contribution of age-related vascular alterations, neuritic pathology and amyloid deposition to the progressive demise of selectively vulnerable neuronal subsetssubserving 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 in the context of schizophrenia and autism spectrum disorder.
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, judgement, and attention, that can be considered as markers of adaptive mechanisms and functions in response to particular ecological pressure.
Visit Dr. Patrick Hof's Laboratory of Neuromorphology for more information.
Amatrudo JM, Weaver CM, Crimins JL, Hof PR, Rosene DL, Luebke JI. Influence of highly distinctive structural properties on the excitability of pyramidal neurons in monkey visual and prefrontal cortices. The Journal of neuroscience : the official journal of the Society for Neuroscience 2012 Oct; 32(40).
Yadav A, Gao YZ, Rodriguez A, Dickstein DL, Wearne SL, Luebke JI, Hof PR, Weaver CM. Morphologic evidence for spatially clustered spines in apical dendrites of monkey neocortical pyramidal cells. The Journal of comparative neurology 2012 Sep; 520(13).
Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, Shen EH, Ng L, Miller JA, van de Lagemaat LN, Smith KA, Ebbert A, Riley ZL, Abajian C, Beckmann CF, Bernard A, Bertagnolli D, Boe AF, Cartagena PM, Chakravarty MM, Chapin M, Chong J, Dalley RA, Daly BD, Dang C, Datta S, Dee N, Dolbeare TA, Faber V, Feng D, Fowler DR, Goldy J, Gregor BW, Haradon Z, Haynor DR, Hohmann JG, Horvath S, Howard RE, Jeromin A, Jochim JM, Kinnunen M, Lau C, Lazarz ET, Lee C, Lemon TA, Li L, Li Y, Morris JA, Overly CC, Parker PD, Parry SE, Reding M, Royall JJ, Schulkin J, Sequeira PA, Slaughterbeck CR, Smith SC, Sodt AJ, Sunkin SM, Swanson BE, Vawter MP, Williams D, Wohnoutka P, Zielke HR, Geschwind DH, Hof PR, Smith SM, Koch C, Grant SG, Jones AR. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 2012 Sep; 489(7416).
Zeng H, Shen EH, Hohmann JG, Oh SW, Bernard A, Royall JJ, Glattfelder KJ, Sunkin SM, Morris JA, Guillozet-Bongaarts AL, Smith KA, Ebbert AJ, Swanson B, Kuan L, Page DT, Overly CC, Lein ES, Hawrylycz MJ, Hof PR, Hyde TM, Kleinman JE, Jones AR. Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures. Cell 2012 Apr; 149(2).
Miller DJ, Duka T, Stimpson CD, Schapiro SJ, Baze WB, McArthur MJ, Fobbs AJ, Sousa AM, Sestan N, Wildman DE, Lipovich L, Kuzawa CW, Hof PR, Sherwood CC. Prolonged myelination in human neocortical evolution. Proceedings of the National Academy of Sciences of the United States of America 2012 Oct; 109(41).
Spocter MA, Hopkins WD, Barks SK, Bianchi S, Hehmeyer AE, Anderson SM, Stimpson CD, Fobbs AJ, Hof PR, Sherwood CC. Neuropil distribution in the cerebral cortex differs between humans and chimpanzees. The Journal of comparative neurology 2012 Sep; 520(13).
Barger N, Stefanacci L, Schumann CM, Sherwood CC, Annese J, Allman JM, Buckwalter JA, Hof PR, Semendeferi K. Neuronal populations in the basolateral nuclei of the amygdala are differentially increased in humans compared with apes: a stereological study. The Journal of comparative neurology 2012 Sep; 520(13).
Nelson PT, Alafuzoff I, Bigio EH, Bouras C, Braak H, Cairns NJ, Castellani RJ, Crain BJ, Davies P, Del Tredici K, Duyckaerts C, Frosch MP, Haroutunian V, Hof PR, Hulette CM, Hyman BT, Iwatsubo T, Jellinger KA, Jicha GA, Kövari E, Kukull WA, Leverenz JB, Love S, Mackenzie IR, Mann DM, Masliah E, McKee AC, Montine TJ, Morris JC, Schneider JA, Sonnen JA, Thal DR, Trojanowski JQ, Troncoso JC, Wisniewski T, Woltjer RL, Beach TG. Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. Journal of neuropathology and experimental neurology 2012 May; 71(5).
Jacot-Descombes S, Uppal N, Wicinski B, Santos M, Schmeidler J, Giannakopoulos P, Heinsen H, Heinsein H, Schmitz C, Hof PR. Decreased pyramidal neuron size in Brodmann areas 44 and 45 in patients with autism. Acta neuropathologica 2012 Jul; 124(1).
Fan J, Xu P, Van Dam NT, Eilam-Stock T, Gu X, Luo YJ, Hof PR. Spontaneous brain activity relates to autonomic arousal. The Journal of neuroscience : the official journal of the Society for Neuroscience 2012 Aug; 32(33).
Gu X, Gao Z, Wang X, Liu X, Knight RT, Hof PR, Fan J. Anterior insular cortex is necessary for empathetic pain perception. Brain : a journal of neurology 2012 Sep; 135(Pt 9).
Heiligenhaus A, Laffers Z. [Congenital lacrimal duct obstructions]. Klinische Monatsblätter für Augenheilkunde 1990 Jan; 196(1).
Gu X, Liu X, Van Dam NT, Hof PR, Fan J. Cognition-emotion integration in the anterior insular cortex. Cerebral cortex (New York, N.Y. : 1991) 2013 Jan; 23(1).
Akram A, Christoffel D, Rocher AB, Bouras C, Kovari E, Perl DP, Morrison JH, Herrmann FR, Haroutunian V, Giannakopoulos P, Hof PR. Stereologic estimates of total spinophilin-immunoreactive spine numbers in area 9 and the CA1 field: relationship with the progression of Alzheimer's disease. . Neurobiol. Aging 2008; 29: 1296-1307.
Rodriguez A, Ehlenberger DB, Dickstein DL, Hof PR, Wearne SL. Automated three-dimensional detection and classification of dendritic spines from fluorescence microscopy. Public Lib. Sci. One 2008; 3(4 ): e1997.
Radley JJ, Rocher AB, Rodriguez A, Ehlenberger DB, Dammann M, McEwen BS, Morrison JH, Wearne SL, Hof PR. Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex. J. Comp. Neurol 2008; 507: 1141-1150.
Hof PR, Van der Gucht E. The structure of the cerebral cortex of the humpback whale, Megaptera novaeangliae (Cetacea, Mysticeti, Balaenopteridae). Anat. Rec 2007; 290: 1-31.
Rodriguez A, Ehlenberger DB, Hof PR, Wearne SL. Rayburst sampling, an algorithm for automated three-dimensional shape analysis from laser scanning microscopy images.. Nature Protocols 2006; 1: 2152-2161.
Hof PR, Morrison JH. The aging brain: morphomolecular senescence of cortical circuits. Trends Neurosci 2004; 27: 607-613.
Bussiere T, Giannakopoulos P, Bouras C, Perl DP, Morrison JH, Hof PR. Progressive degeneration of nonphosphorylated neurofilament protein-enriched pyramidal neurons predicts cognitive impairment in Alzheimer's disease: a stereologic analysis of prefrontal cortex area 9. J. Comp. Neurol 2003; 463: 281-302.
Luebke JI, Weaver CM, Rocher AB, Rodriguez A, Crimins JL, Dickstein DL, Wearne SL, Hof PR. Dendritic vulnerability in neurodegenerative disease: insights from analyses of cortical pyramidal neurons in transgenic mouse models.. Brain Structure and Function 2010 Mar; 214(2,3): 181-199.
Kabaso D, Koskren PJ, Henry BI, Hof PR, Wearne SL. The electrotonic structure of pyramidal neurons contributing to prefrontal cortical circuits in macaque monkeys is significantly altered in aging.. Cerebral Cortex 2009 Oct; 19(10): 2248-2268.
Butti C, Sherwood CC, Hakeem AY, Allman JM, Patrick R. Hof PR. Total number and volume of von Economo neurons in the cerebral cortex of cetaceans.. Journal of Comparative Neurology 2009 Jul; 515(2): 243-259.
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Dr. Hof did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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