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Katerina Semendeferi

Katerina Semendeferi is Professor of Anthropology and Director of the Laboratory for Human Comparative Neuroanatomy at UC San Diego. Originally from Thessaloniki Greece, she completed her graduate and postgraduate training in Biological Anthropology, Neurosciences and the program in Cognitive Neuroscience at the University of Iowa before joining the faculty at UC San Diego.  Semendeferi’s scientific inquiry in “what makes us human” is grounded in the comparative study of the brain. Her long-standing commitment to noninvasive approaches to study the brain, helped her pioneer new ways to gain insights into the neuroanatomy of great apes, our closest living relatives, compared to humans. More recently she begun to explore links between the phylogenetically reorganized brain regions and their implication in vulnerabilities observed in atypical human neurodevelopment. 

Her work demonstrated that, contrary to dominant views, the relative size of the frontal cortex is remarkably similar across apes and humans (PMID: 11850633) and that instead of an overall disproportionate enlargement of this functionally important part of the brain, evolutionary modifications took place in more subtle aspects of the anatomy, like specific areas within the frontal lobe, density of neurons, cortical layers, neuronal subtypes and in interconnected subcortical nuclei like the amygdala (PMID: 21098620; PMID:22473387). These findings point to a phylogenetically recent reorganization of circuitry (PMID: 24904348) that may be critical to the emergence of altered communication between brain regions regulating human-specific cognitive and emotional functions (PMID: 31703898). Atypical neurodevelopment in these same systems underlie Autism (ASD) (PMID: 22068992) and Williams Syndrome (WS) (PMID: 32189114; PMID: 30501059; PMID: 28848376) with some neural alterations taking place in opposing directions, as recently discovered (PMID: 32024554). Both ASD and WS are characterized by distinct socio-cognitive abilities and can thus help elucidate the evolutionary interplay between genes, environment, brain structure and behavior (PMID: 25247986; PMID: 31260092).

Semendeferi’s interest in the field of comparative neuroanatomy goes beyond the pursuit of discoveries in her own laboratory. Her initiatives triggered transformations in the field of human brain evolution and the comparative study of the ape brain in the last two decades. Early on she established collaborations with zoos and veterinarians across the U.S. aimed to make available to science the brains of apes, following the natural death of individual animals (PMID: 11241188; PMID: 9637180). Precious tissue, previously disposed of, started to be systematically collected and then curated by her and others leading to large and unique data sets available to scientists around the world. 

Semendeferi initiated the application of structural Magnetic Resonance Imaging technology on postmortem ape brain specimens (PMID: 9085187) and a postdoctoral NIH fellowship allowed her to pursue the initiation of scanning of the brain of living apes with collaborators at the Yerkes Primate Research Center which led to the successful testing and application of the novel noninvasive technology on the brain of an initial cohort of apes and humans (PMID: 10656781).  These early initiatives planted the seeds for the establishment of ape and other primate brain banks and the subsequent larger scale application of noninvasive imaging techniques on living apes in the U.S. Numerous dissertations and hundreds of scientific papers can be linked to the resources she first pursued and the partnerships she fostered over time.

Semendeferi is currently collaborating with pioneers in the field of induced pluripotent stem cells and brain organoids in an effort to bridge human neuroanatomy with this novel technology using living cells in the dish (PMID: 27509850) in ways that can be mutually informative and move the field of human brain evolution to the future (PMID:30730291; Science 2021). In her laboratory she analyzes postnatal and adult human tissue in partnership with the University of Maryland Brain and Tissue Bank, a repository of the National Institutes of Health NeuroBioBank. Fetal human brain tissue sections are housed in collections at the National Museum of Health and Medicine, Washington D.C

Although her specialization is in human comparative neuroanatomy, Semendeferi has been exposed to other approaches to the study of human evolution, including the fossil record, and maintains a sustained interest in bringing together multiple fields of inquiry (PMID: 24194709; PMID: 29533941). She was involved in archeological and paleoanthropological excavations in the United States, Europe and Asia and has been teaching undergraduate and graduate courses on Human Origins, Human Comparative Neuroanatomy, Human Brain Evolution, Honors Studies in Anthropology, core graduate seminar in Biological Anthropology and other courses. She has a commitment to training and mentoring a diverse student body, including first generation college students, underrepresented minorities, women of various ethnic backgrounds and others.  Semendeferi is the recipient of the Faculty Outstanding Mentor Award for Marshall College at UC San Diego. She gave the James Arthur Lecture on Human Brain Evolution in the American Museum of Natural History in NY and is faculty in the Neuroscience Program, advisory board member of the Kavli Institute for Brain and Mind, and internal adviser for the Center of Academic Research and Training in Anthropogeny (CARTA) at UC San Diego. She is Elected Fellow of the American Association for the Advancement of Science.

Atypical Human Neurodevelopment 

Morgan*, J.T., Gursharan, C., I. Abramson, K. Semendeferi, E. Courchesne, and I. P. Everall (2012) Abnormal microglial-neuronal spatial organization in the dorsolateral prefrontal cortex in autism Brain Research1456:72-81.

Teffer*, K and K. Semendeferi (2012) Human prefrontal cortex: evolution, development, and pathology. M. A. Hofman and D. Falk (Eds.) Progress in Brain Research, 195:191-218.

Courchesne, E, Mouton P.R., Calhoun, M.E., Semendeferi, K., Ahrens-Barbeau, C., Hallet, M.J., Carter-Barnes, C., Pierce, K (2011) Neuron Number and Size in Prefrontal Cortex of Children With Autism. JAMA 306(18): 2001-2010.

Morgan*, J.T., Chana, G., Pardo-Villamizar, C., Achim, C., Semendeferi, K., Buckwalter*, J., Courchesne, E., & Everall, I.P. (2010) Increased Microglial Activation and Cell Density in the Dorsolateral Prefrontal Cortex in Autism. Biological Psychiatry, 68:368–376.

Kennedy*, D.P., K. Semendeferi, E. Courchesne  (2007) No reduction of spindle neuron number in frontoinsular cortex in autism. Brain and Cognition, 64:124-129.

Buxhoeveden, D.P., K. Semendeferi, J. Buckwalter*, N. Schenker*, R. Switzer, E. Courchesne (2006) Reduced minicolumns in the frontal cortex of patients with autism. Neuropathology and Applied Neurobiology, 32:483-491.

Van Hoesen, G.W., Morecraft, R.J. and Semendeferi, K. (1996) Functional neuroanatomy of the limbic system and prefrontal cortex. In B. Fogel, R.B. Schiffer and S.M. Roa (Eds.) Neuropsychiatry: A Comprehensive Textbook, William & Wilkins, Baltimore, pp. 113-143.

* Indicates that the author is/was an undergraduate, graduate or postdoctoral student  supervised by Semendeferi at the time of manuscript preparation.

Human Brain Evolution

Kate Teffer*, Daniel Buxhoeveden, Cheryl D. Stimpson, Archibald J. Fobbs, Steven J. Schapiro, Wallace B. Baze, Mark J. McArthur, William Hopkins, Patrick Hof, Chet C. Sherwood and K. Semendeferi Developmental changes in the spatial organization of neurons in the neocortex of humans and chimpanzees. Journal of Comparative Neurology, In Press.

Branka Hrvoj*, Maria C. N. Marchetto, Fred H. Gage, K. Semendeferi & Alysson R. Muotri. Novel tools, classic techniques: Evolutionary studies using primate pluripotent stem cells Biological Psychiatry, In Press.

Bianchi S, C.D. Stimpson, A.L.Bauernfield, S.J. Schapiro, W.B. Baze, M.J. McArthur, E. Bronson, W.D. Hopkins, K. Semendeferi, B. Jacobs, P.R. Hof, and C.C. Sherwood.Dendritic morphology of pyramidal neurons in the chimpanzee neocortex: regional specializations and comparisons to humans. Cerebral Cortex, In Press.

A.L. Bauernfeind, A.A. de Sousa, T. Avasthi, S.D. Dobson, M.A. Raghanti, A.H. Lewandowski, K. Zilles, K. Semendeferi, J.M. Allman, A.D. Craig, P.R. Hof, and C.C. Sherwood (2013A volumetric comparison of the insular cortex and its subregions in primates. Journal of Human Evolution 64:263-279

Barger* N, Stefanacci L, Schumann C, Annese J, Sherwood C, Allman J, Buckwalter J,

Hof P and K. Semendeferi (2012) Neuronal populations in the basolateral nuclei of the amygdala are differentially increased in humans compared to apes: A stereological study. Journal of Comparative Neurology, 520(13):3035-3054.

Teffer*, K and K. Semendeferi (2012) Human prefrontal cortex: evolution, development, and pathology.M. A. Hofman and D. Falk (Eds.) Progress in Brain Research, 195:191-218.

Allman,J.M., Tetreault,N.A., Hakeem, A.Y., Kebreten F. Manaye, K. Semendeferi, Joseph M. Erwin, Soyoung Park, Virginie Goubert, and Patrick R. Hof (2011) The von Economo neurons in the frontoinsular and anterior cingulate cortex. Ann. N.Y. Acad. Sci.1225: 59–71.

Semendeferi, K., K.Teffer*, D.P. Buxhoeveden, M.S. Park*, S. Bludau, K. Amunts, K.Travis*, J. Buckwalter*. (2011) Spatial organization of neurons in the prefrontal cortex sets humans apart from great apes. Cerebral Cortex, 21:1485—1497.

Semendeferi, K., N. *Barger, N. *Schenker (2010) Brain reorganization in humans and apes. In: Human Brain Evolving. D. Broadfield, M. Yuan, N. Toth, and K. Schick (Eds) Stone Age Institute Press (4th volume). David Brown Book Company and Oxbow Books, 119-155.

Allman, J.M., Tetreault, N.A., Hakeem, A.Y., Manaye, K.F., Semendeferi, K., Erwin, J.M., Goubert, V., and Hof, P.R. (2010) The von Economo Neurons in Frontoinsular and Anterior Cingulate Cortex in Great Apes and Humans. Brain Structure and Function,214:495–517.

Carlo, C.N., L. Stefanacci, K. Semendeferi, C.F. Stevens (2010) Comparative analyses of the neuron numbers and volumes of the amygdaloid complex in old and new world primates, Journal of Comparative Neurology, 518(8):1176-1198.

Schenker*, N.M., D.P Buxhoeveden, W.L. Blackmon, K. Amunts, K. Zilles and K. Semendeferi  (2008) A comparative quantitative analysis of cytoarchitectonics and minicolumnar organization in Broca's area in humans and great apes. Journal of Comparative Neurology, 510:117-128.

Schenker*, N., C.C. Sherwood, P.R. Hof, and K. Semendeferi (2007) Microstructural asymmetries of the cerebral cortex in humans and other mammals. In: Special Topics in Primatology, W.D. Hopkins (ed), Elsevier, Inc., pp 92-118.

Barger*, N., Stefanacci, L., Semendeferi, K. (2007) A comparative volumetric analysis of the amygdaloid complex and basolateral division in the human and ape brain. American Journal of Physical Anthropology, 134(3):392-403.

Park*, M.S., Nguyen, A.D., Aryan, H.E., Sang, H., Levy, M.L., Semendeferi, K.  (2007)Evolution of the human brain: Changing brain size and the fossil record. Neurosurgery60:555-562.

Sherwood, C.C., Holloway, R.L., Semendeferi, K., Hof, P.R. (2005) Is prefrontal white matter enlargement a human evolutionary specialization? Nature Neuroscience 8(5):537-538.

Schenker*, N., Desgouttes*, A.M and Semendeferi, K. (2005) Neural connectivity and cortical substrates of cognition in hominoids. Journal of Human Evolution 49:547-569.

Sherwood, C.C., Hof, P.R., Holloway, R.L., Semendeferi, K., Gannon, P.J., Frahm, H., and Zilles, K.  (2005) Evolution of the brainstem orofacial motor system in primates: a comparative quantitative study of trigeminal, facial and hypoglossal motor nuclei.

Journal of Human Evolution, 48:45-84.

Sherwood CC, Holloway RL, Gannon PJ, Semendeferi K, Erwin JM, Zilles K, and Hof PR (2003) Neuroanatomical basis of facial expression in monkeys, apes, and humans. Ann. N Y Acad. Sci. 1000:1-5.

Semendeferi, K., *Lu, A., *Schenker, N., and Damasio, H. (2002)  Humans and great apes share a large frontal cortex. Nature Neuroscience 5(3):272-276.

Semendeferi, K.  (2001) Advances in the study of hominoid brain evolution: Magnetic Resonance Imaging (MRI) and 3D reconstruction. In D. Falk and K. Gibson (Eds.) Evolutionary Anatomy of the Primate Cerebral Cortex Cambridge, U.K.: Cambridge University Press.

Semendeferi, K., Schleicher, A., Zilles, K, Armstrong, E. and Van Hoesen, G.W. (2001)Prefrontal cortex in humans and apes: A comparative study of area 10. American Journal of Physical Anthropology 114(3):224-241.

Semendeferi, K. (2001) Before or after the split? Hominid neural specializations.  In A. Nowell  (Ed.) In the Mind’s Eye: Multidisciplinary Perspectives on the evolution of Human Cognition.  University of Michigan Press, Ann Arbor, International Monograph Series, pp 107-120.

Semendeferi, K. and Damasio, H.  (2000) The brain and its main anatomical subdivisions in living hominoids using magnetic resonance imaging. Journal of Human Evolution, 38: 317-332.

Semendeferi, K. (1999) The frontal lobes of the great apes with a focus on the gorilla and the orangutan. In S.T. Parker, R.W. Mitchell and H.L. Miles (Eds.) The Mentality of Gorillas and Orangutans: Comparative Perspectives, Cambridge University Press, Cambridge, U.K., pp. 70-95.

Semendeferi, K., Armstrong, E., Schleicher, A., Zilles, K., and Van Hoesen, G.W. (1998) Limbic frontal cortex in hominoids: A comparative study of area 13. American Journal of Physical  Anthropology, 106:129-155.

Semendeferi, K., Damasio, H., Frank, R. and Van Hoesen, G.W. (1997) The evolution of the frontal lobes: a volumetric analysis based on three-dimensional reconstructions of magnetic resonance scans of human and ape brains. Journal of Human Evolution, 32: 375-388.

* Indicates that the author is/was an undergraduate, graduate or postdoctoral student  supervised by Semendeferi at the time of manuscript preparation.