Hof Lab

Laboratory of Neuromorphology

Research

patrick hofOur 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 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 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 autism spectrum disorders, drug-resistant epilepsy, and chronic traumatic encephalopathy.

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.

Contact Us

Hof Laboratory
Patrick R Hof, MD
Professor, Neuroscience
Professor, Ophthalmology
Professor, Geriatrics and Palliative Medicine
Location
Lab: HESS 10-302
Office: HESS 10-118
Phone
Office: 212.824.9302
Lab: 212.824.9172
Email

Featured

The Human Brain Atlas

Ding S.L., Royall J.J., Sunkin S.M., Ng L., Facer B.A.C., Lesnar P., Guillozet-Bongaarts A., McMurray B., Szafer A., Dolbeare T.A., Stevens A., Tirrell L., Benner T., Caldejon S., Dalley R.A., Dee N., Lau C., Nyhus J., Reding M., Riley Z.L., Sandman D., Shen E., van der Kouwe A., Varjabedian A., Write M., Zollei L., Dang C., Knowles J.A., Koch C., Phillips J.W., Sestan N., Wohnoutka P., Zielke H.R., Hohmann J.G., Jones A.R., Bernard A., Hawrylycz M.J., Hof P.R., Fischl B., Lein E.S. (2016) Comprehensive cellular-resolution atlas of the adult human brain. J. Comp. Neurol. 524(16):3127-3481, doi:10.1002/cne.24080.

Publications

2017

Harony-Nicolas H., Kay M., du Hoffmann J., Klein M.E., Bozdagi-Gunal O., Riad M., Daskalakis N.P., Sonar S., Castillo P.E., Hof P.R., Shapiro M.L., Baxter M.G., Wagner S., Buxbaum J.D. (2017) Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat. eLife 6, e18904.


Simic G., Babic Leko M., Wray S., Harrington C.R., Delalle I., Jovanov-Milosevic N., Bazadona D., Buée L., de Silva R., Di Giovanni G., Wischik C.M., Hof P.R. (2017) Monoaminergic neuropathology in Alzheimer’s disease. Prog. Neurobiol. 151, 101-138.


Li Q., Bozek K., Xu C., Guo Y., Sun J., Pääbo S., Sherwood C.C., Hof P.R., Ely J.J., Li Y., Willmitzer L., Giavalisco P., Khaitovich P. (2017) Changes in lipidome composition during brain development in humans, chimpanzees, and macaque monkeys. Mol. Biol. Evol.  34, 1155-1166.

2016

Ding S.L., Royall J.J., Sunkin S.M., Ng L., Facer B.A.C., Lesnar P., Guillozet-Bongaarts A., McMurray B., Szafer A., Dolbeare T.A., Stevens A., Tirrell L., Benner T., Caldejon S., Dalley R.A., Dee N., Lau C., Nyhus J., Reding M., Riley Z.L., Sandman D., Shen E., van der Kouwe A., Varjabedian A., Write M., Zollei L., Dang C., Knowles J.A., Koch C., Phillips J.W., Sestan N., Wohnoutka P., Zielke H.R., Hohmann J.G., Jones A.R., Bernard A., Hawrylycz M.J., Hof P.R., Fischl B., Lein E.S. (2016) Comprehensive cellular-resolution atlas of the adult human brain. J. Comp. Neurol. 524(16):3127-3481, doi:10.1002/cne.24080.


Babic Leko M., Borovecki F., Dejanovic N., Hof P.R., Simic G. (2016) Predictive value of cerebrospinal fluid visinin-like protein-1 levels for Azheimer’s disease early detection and differential diagnosis in patients with mild cognitive impairment. J. Alzheimer Dis. 50, 765-778.


Perez S.E., Sherwood C.C., Cranfield M.R., Erwin J.M., Mudakikwa A., Hof P.R., Mufson E.J. (2016) Early Alzheimer’s disease-type pathology in the frontal cortex of wild mountain gorillas (Gorilla beringei beringei). Neurobiol. Aging 39, 195-201.


Stimpson C.D., Barger N., Taglialatella J.P., Gendron-Fitzpatrick A., Hof P.R., Hopkins W.D., Sherwood C.C. (2016) Differential serotonergic innervation of the amygdala of bonobos and chimpanzees. Soc. Cogn. Affect. Neurosci. 11, 413-422.


Jacobs B., Lee L., Schall M., Raghanti M.A., Lewandowski A.H., Kottwitz J.J., Roberts J.F., Hof P.R., Sherwood C.C. (2016) Neocortical neuronal morphology in the newborn giraffe (Giraffa camelopardalis tippelskirchi) and African elephant (Loxodonta africana). J. Comp. Neurol. 524, 257-287.


Raghanti M.A., Edler M.K., Stephenson A.R., Wilson L.J., Hopkins W.D., Ely J.J., Erwin J.M., Jacobs B., Hof P.R., Sherwood C.C. (2016) Human-specific increase of dopaminergic innervation in a striatal region associated with speech and language: a comparative analysis of the primate basal ganglia. J. Comp. Neurol. 524, 2217-2129.


Lipovich L., Hou Z.C., Jia H., Sinkler C., McGowen M., Sterner K.N., Weckle A., Sugalski A.B., Pipes L., Gatti D.L., Mason C.E., Sherwood C.C., Hof P.R., Kuzawa C.W., Grossman L.I., Goodman M., Wildman D.E. (2016) High-throughput RNA sequencing reveals structural differences of orthologous brain-expressed genes between western lowland gorillas and humans. J. Comp. Neurol. 524, 288-308.


Xuan B., Mackie M.A., Spagna A., Wu T., Tian Y., Hof P.R., Fan J. (2016) The activation of interactive attentional networks. NeuroImage 129, 308-319.

2015

Wegiel J., Flory M., Kuchna I., Nowicki K., Ma S., Imaki H., Wegiel J., Frackowiak J., Kolecka B., Wierzba-Bobrowicz T., London E., Wisniewski T., Hof P.R., Brown T. (2015) Neuronal nucleus and cytoplasm volume deficit in children with autism and volume increase in adolescents and adults. Acta Neuropathol. Commun. 3, 2.


Bozek K., Wei Y., Yan Z., Liu X., Xiong J., Sugimoto M., Tomita M., Pääbo S., Sherwood C.C., Hof P.R., Ely J.J., Li Y., Steinhauser D., Willmitzer L., Giavalisco P., Khaitovich P. (2015) Organization and evolution of brain lipidome revealed by large-scale analysis of human, chimpanzee, macaque, and mouse tissues. Neuron 85, 695-702.


Barks S.K., Calhoun M.E., Hopkins W.D., Cranfield M.R., Paterson P.E., Mudakikwa A., Erwin J.M., Stoinski T.S., Hecht E.E., Hof P.R., Sherwood C.C. (2015) Brain organization of gorillas reflects species differences in ecological specialization. Am. J. Phys. Anthropol. 156, 252-262.


Coskren P.J., Luebke J.I., Kabaso D., Wearne S.L., Yadav A., Rumbell T., Hof P.R., Weaver C.M. (2015) Functional consequences of age-related morphologic changes to pyramidal neurons of the rhesus monkey prefrontal cortex. J. Comput. Neurosci. 38, 263-283.


Luebke J.I., Medalla M., Amatrudo J.M., Weaver C.M., Crimins J.L., Hunt B., Hof P.R., Peters A. (2015) Age-related changes to layer 3 pyramidal cells in the rhesus monkey visual cortex. Cereb. Cortex 25, 1454-1468.


Uppal N., Puri R., Yuk F., Janssen W.G.M., Bozdagi-Günal O., Harony-Nicolas H., Dickstein D.L., Buxbaum J.D., Hof P.R. (2015) Ultrastructural changes in the CA1 of Shank3-deficient mice. Mol. Autism 6, 41.
Gu X., Eilam-Stock T., Zhou T., Anagnostou E., Kolevzon A., Soorya L., Hof P.R., Friston K.L., Fan J. (2015) Autonomic and brain responses associated with empathy deficits in autism spectrum disorder. Hum. Brain Mapp. 36, 3323-3338.


Raghanti M.A., Spurlock L.B., Treichler F.R., Weigel S.E., Stimmelmayr R., Butti C., Thewissen J.G.M.H., Hof P.R. (2015) An analysis of von Economo neurons in the cerebral cortex of cetaceans, artiodactyls, and perissodactyls. Brain Struct. Funct. 220, 2303-2314.


Bauernfeind A.L., Reyzer M.L., Caprioli R.M., Ely J.J., Babbitt C.C., Wray G.A., Hof P.R., Sherwood C.C. (2015) High spatial resolution proteomic comparison of the brain in humans and chimpanzees. J. Comp. Neurol. 523, 2043-2061.


Brautigam H., Moreno C.L., Steele J.W., Bogush A., Dickstein D.L., Kwok J.B.J., Schofield P.R., Thinakaran G., Mathews P.M., Hof P.R., Gandy S., Ehrlich M.E. (2015) Physiologically generated presenilin 1 lacking exon 8 fails to rescue brain PS1-/- phenotype and forms complexes with wildtype PS1 and nicastrin. Sci. Rep. 5, 17042.

2014

Barks S.K., Bauernfeind A.L., Bonar C.J., Cranfield M.R., de Sousa A.A., Erwin J.M., Hopkins W.D., Lewandowski A.H., Mudakikwa A., Phillips K.A., Raghanti M.A., Stimpson C.D., Hof P.R., Zilles K., Sherwood C.C. (2014) Variable temporoinsular cortex neuroanatomy in primates suggests bottleneck effect in eastern gorillas. J. Comp. Neurol. 522, 844-860.


Eilam-Stock T., Xu P., Cao M., Gu X., Van Dam N.T., Anagnostou E., Kolevzon A., Soorya L., Park Y., Siller M., He Y., Hof P.R., Fan J. (2014) Abnormal autonomic and associated brain activities during rest in autism spectrum disorder. Brain 137, 153-171.


Uppal N., Giannatiempo I., Wicinski B., Schmeidler J., Heinsen H., Schmitz C., Buxbaum J.D., Hof P.R. (2014) Neuropathology of the posteroinferior occipital gyrus in children with autism. Mol. Autism. 5, 17.


Guillozet-Bongaarts A.L., Hyde T.M., Dalley R.A., Hawrylycz M.J., Henry A., Hof P.R., Hohmann J., Jones A.R., Kuan C.L., Royall J., Shen E., Swanson B., Zeng H., Kleinmann J.E. (2014) Altered gene expression in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol. Psychiatry 19, 478-485.


Butti C., Fordyce R.E., Raghanti M.A., Gu X., Bonar C.J., Wicinski B.A., Wong E.W., Roman J., Brake A., Eaves E., Spocter M.A., Tang C.Y., Jacobs B., Sherwood C.C., Hof P.R. (2014) The cerebral cortex of the pygmy hippopotamus, Hexaprotodon liberiensis (Cetartiodactyla, Hippopotamidae): MRI, cytoarchitecture, and neuronal morphology. Anat. Rec. 297, 670-700.


Bozek K., Wei Y., Yan Z., Liu X., Xiong J., Sugimoto M., Tomita M., Pääbo S., Pieszek R., Sherwood C.C., Hof P.R., Ely J.J., Steinhauser D., Willmitzer L., Bangsbo J., Hansson O., Call J., Giavalisco P., Khaitovich P. (2014) Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness. PLoS Biol. 12(5), e1001871.


Uppal N., Wicinski B., Buxbaum J.D., Heinsen H., Schmitz C., Hof P.R. (2014) Neuropathology of the anterior midcingulate cortex in young children with autism. J. Neuropathol. Exp. Neurol. 73, 891-902.

2013

Van Dam N.T., Sano M., Mitsis E.M., Grossman H.T., Gu X., Park Y., Hof P.R., Fan J. (2013) Functional neural correlates of attentional deficits in amnestic mild cognitive impairment. PLoS One 8(1), e54035.


DeFelipe J., López-Cruz P.L., Benavides-Piccione R., Bielza C., Larrañaga P., Anderson S., Burkhalter A., Cauli B., Fairén A., Feldmeyer D., Fishell G., Fitzpatrick D., Freund T.F., González-Burgos G., Hestrin S., Hill S., Hof P.R., Huang J., Jones E.G., Kawaguchi Y., Kisvarday Z., Kubota Y., Lewis D.A., Marín O., Markram H., McBain C.J., Meyer H.S., Monyer H., Nelson S.B., Rockland K., Rossier J., Rubinstein J.L.R., Rudy B., Scanziani M., Shepherd G.M., Sherwood C.C., Staiger J.F., Tamás G., Thomson A., Wang Y., Yuste R., Ascoli G.A. (2013) New insights into the classification and nomenclature of cortical GABAergic interneurons. Nat. Rev. Neurosci. 14, 202-216.


Höistad M., Heinsen H., Wicinski B., Schmitz C., Hof P.R. (2013) Stereological assessment of the dorsal anterior cingulate cortex in schizophrenia: absence of changes in neuronal and glial densities. Neuropathol. Appl. Neurobiol. 39, 348-361.


Bianchi S., Stimpson C.D., Duka T., Larsen M.D., Janssen W.G.M., Collins Z., Bauernfeind A.L., Schapiro S.J., Baze W.B., McArthur M.J., Hopkins W.D., Wildman D.E., Lipovich L., Kuzawa C.W., Jacobs B., Hof P.R., Sherwood C.C. (2013) Synaptogenesis and development of pyramidal neuron dendritic morphology in the chimpanzee neocortex resembles humans. Proc. Natl. Acad. Sci. USA 110 (Suppl. 2), 10395-10401.


J Comp NeurolGu X, Hof PR, Friston KL, Fan J. Anterior insular cortex and emotional awareness. J Comp Neurol 2013;521:3371-3388.PMID: 23749500


cereb cortex 2013Gu X, Liu X, Van Dam NT, Hof PR, Fan J. Cognition-emotion integration in the anterior insular cortex. Cereb Cortex. 2013;23:20-27. PMID: 22275476

2012

J Neurosci 2012Amatrudo 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. J Neurosci. 2012;32:13644-13660. PMID: 23035077


j comp neurol 2012 520Yadav 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. J Comp Neurol. 2012;520:2888-2902. PMID: 22315181


nature 2012 489Hawrylycz 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;489:391-399. PMID: 22996553


cell 2012 149Zeng 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;149:483-496. PMID: 22500809


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. Proc Natl Acad Sci USA. 2012;109:16480-16485. PMID: 23012402


j comp neurol 2012 520Spocter 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. J Comp Neurol. 2012;520:2917-2929. PMID: 22350926


j comp neurol 2012 520Barger 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. J Comp Neurol. 2012;520:3035-3054. PMID: 22473387


j neuropathol exp neurol 2012 71Nelson 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. J Neuropathol Exp Neurol. 2012;71:362-381. PMID: 22487856


acta neuropathol 2012 124Jacot-Descombes S, Uppal N, Wicinski B, Santos M, Schmeidler J, Giannakopoulos P, Heinsen H, Schmitz C, Hof PR. Decreased pyramidal neuron size in Brodmann areas 44 and 45 in patients with autism. Acta Neuropathol. 2012;124:67-79. PMID: 22467063


Fan J, Xu P, Van Dam NT, Eilam-Stock T, Gu X, Luo Y, Hof PR. Spontaneous brain activity relates to autonomic arousal. J Neurosci. 2012;32:11176-11186. PMID: 22895703


brain 2012 135Gu X, Gao Z, Wang X, Liu X, Knight RT, Hof PR, Fan J. Anterior insular cortex is necessary for empathetic pain perception. Brain. 2012;135:2726-2735. PMID: 22961548


brain behav 2012 2Fan J, Bernardi S, Dam NT, Anagnostou E, Gu X, Martin L, Park Y, Liu X, Kolevzon A, Soorya L, Grodberg D, Hollander E, Hof PR. Functional deficits of the attentional networks in autism. Brain Behav. 2012;2:647-660. PMID: 2313991

Meet the Team

Camilla Butti

Visiting Scientist

camilla buttiI received my Ph.D. in Biomedical and Comparative Veterinary Sciences from the University of Padova, Italy, where I began working on the organization of the cetacean cerebral cortex. My interests are in comparative brain evolution studying how different cortical organizations among mammals support similar functions. My current research focuses on the qualitative and quantitative analysis of the cytoarchitecture of frontal cortical regions, in a wide range of marine and terrestrial mammals, with a particular emphasis on neuronal specializations.
camilla.butti@mssm.edu

Bridget A. Wicinski

Laboratory Manager

wicinski bridgetAs lab manager, I am responsible for the daily function of the laboratory. I maintain the microscopes and computers of our quantitative microscopy stations and train students, postdocs, and staff in their proper use. I also train laboratory personnel in a variety of histologic techniques, which allows me to support the experimental work of our ongoing projects. I also catalogue and manage Dr. Hof’s extensive collection of mammalian brain specimens and prepared slides.
bridget.wicinski@mssm.edu

Merina Varghese

Instructor

merina varghesePathological changes in the brain occurring in neurological and psychiatric diseases drive my research interest. My previous research has uncovered biochemical changes, specifically mitochondrial dysfunction and protein aggregation, occurring in animal and cellular models of various neurodegenerative disorders. I am currently investigating changes in neuronal structure in a rat model of Phelan-McDermid syndrome. My studies will compare dendritic and synaptic morphology in the hippocampus and prefrontal cortex of Shank3 rats to the wild-type using confocal and electron microscopic imaging. My goal is to contribute to understanding how deletions of the Shank3 protein affect synaptic structure and function in autism spectrum disorders.
merina.varghese@mssm.edu

Sarah Jacot-Descombes

Post Doc

sarah jacot descombesI am an MD specializing in child and adolescent psychiatry at the University of Geneva, Switzerland. I was a research scholar in the Hof lab in 2011, studying the pathology of the mirror neuron system in autism spectrum disorder. I returned as a postdoc with a project focusing on understanding how the deletion of the SHANK3 gene affects synaptic structure in a model of autism spectrum disorder. I am also working with the Seaver Autism Center on assessing visual evoked potentials as a method to monitor treatment in children with severe autism.
sarah.jdc@gmail.com

Tahia Warda

Tahia Warda

Associate Researcher II

tahia.warda@mssm.edu

Lizette Couto

Lizette Couto

Graduate (MS) student

Lizette.Couto@icahn.mssm.edu

Marie Kopp

Marie Kopp

Grants Coordinator

marie.kopp@mssm.edu