Daniel Geschwind

Last updated
Daniel H. Geschwind
Alma mater Dartmouth College, Yale School of Medicine
Awards
Scientific career
Fields Human genetics, neurogenetics
Institutions University of California, Los Angeles
Doctoral advisor Susan Hockfield

Daniel H. Geschwind is an American physician-scientist whose laboratory has made pioneering discoveries in the biology of brain disorders and the genetic and genomic analyses of the nervous system.

Contents

His laboratory showed that gene co-expression has a reproducible network structure that can be used to understand neurobiological mechanisms in health, evolution, and disease. [2] [3] [4] He led the first studies to define the molecular pathology of autism spectrum disorder (ASD) and several other psychiatric disorders, [5] [6] [7] and has made major contributions to defining the genetic basis of autism. [8] [9] [10]

Currently, he is the Gordon and Virginia MacDonald Distinguished Professor of Human Genetics, Neurology and Psychiatry at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA). He also directs the UCLA Neurogenetics Program and the UCLA Center for Autism Research and Treatment (CART). [11] [12] Since March 2016 he has served as the Senior Associate Dean and Associate Vice Chancellor for Precision Health at UCLA. [13]

Education and career

Geschwind received his A.B. degree in psychology and chemistry at Dartmouth College, and his MD/PhD at Yale School of Medicine under the supervision of Susan Hockfield , graduating Alpha Omega Alpha. [14] [12] He then completed an internship in internal medicine and residency in neurology at UCLA. [11] He has been a member of the UCLA faculty since 1997. [12]

He has trained over 70 graduate students and post-doctoral research fellows, [15] and is among the highest cited scientists in neurology, neuroscience, systems biology, and precision health (H index > 195). [16] He has been named in Clarivate Analytics’ Highly Cited Researchers list each year since 2017 [17] and has been elected as member of the National Academy of Medicine and the Association of American Physicians. [18]

Research

The Geschwind Lab at the UCLA David Geffen School of Medicine conducts research into three areas: autism and neurodevelopmental disorders, neurodegenerative syndromes, and human brain evolution. [12] [19] The overarching goal of Geschwind's work is to develop a more mechanistic understanding of neurodevelopmental and neurodegenerative diseases by integrative analyses that connect human genetic variation to genes and neurobiological pathways.

Through functional genomics and large-scale data analyses that permit a more unbiased understanding of disease mechanisms, his laboratory's research has improved  our understanding of human brain evolution and language, ASD and schizophrenia, repair of the damaged nervous system and neurodegenerative dementias including Frontotemporal Dementia, Progressive Supranuclear Palsy and Alzheimer's disease. Together these studies have not only improved understanding of human brain disorders, but they also highlight the power of highly-parallel, high-throughput  biology. [20]

Geschwind established the modern era of autism genetics research by developing and leading the Autism Genetic Resource Exchange (AGRE) [21] with the Cure Autism Now Foundation in 1997. AGRE was the first major community resource for genetic research on autism spectrum disorder (ASD), making biomaterials and phenotype data accessible to researchers worldwide. This initiative opened the field to many more researchers and led to significant discoveries, including the role of rare mutations and inherited genetic variation in ASD. [10] He is an advocate for data sharing and led many national efforts, including PsychENCODE consortium, a public genomic data resource for mental health research. Over the last 10 years, he has led efforts with collaborators, including John Constantino and Ami Klin, to increase the representation of groups that have been historically underrepresented in autism research, via an NIH-funded Autism Center of Excellence Network that recruits African Americans with autism. [10]

His work in autism genetics and functional genomics has been highly influential by translating genetic findings into biological understanding. He developed the concept of ASD as a developmental disconnection syndrome, recognizing its extreme heterogeneity and framing it as “the autisms.” Geschwind pioneered the study of language and social endophenotypes in genetic studies and demonstrated how transcriptomic and epigenetic profiling could define the molecular pathology of ASD and other neuropsychiatric disorders. In 2011, he was the senior author of a study that identified chemical differences between the brains of people with autism and those without it. [22] Specifically, the study found common patterns in gene expression in the frontal and temporal lobes of autistic individuals. Geschwind has published research on numerous genes involved in language and human brain evolution, such as FOXP2, and how they differ between humans and chimpanzees. Additionally, Geschwind is known for his research into factors affecting handedness and the differences in brain structure between left-handed and right-handed people.

Personal life

His brother, Michael Geschwind, is also a professor of neurology. Norman Geschwind, a pioneer in behavioral neurology, is his father's first cousin. From 1965 to 1982, his father, Stanley Geschwind, served as the head of the Quantum and Solid-State Physics Department at Bell Labs. [23] [24] [8]

Awards and prizes

Related Research Articles

<span class="mw-page-title-main">Conditions comorbid to autism</span> Medical conditions more common in autistic people

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that begins in early childhood, persists throughout adulthood, and affects me in this way: social communication and restricted, repetitive patterns of behavior. There are many conditions comorbid to autism spectrum disorder, such as attention deficit hyperactivity disorder, anxiety disorders, and epilepsy.

Neurodevelopmental disorders are a group of mental conditions affecting the development of the nervous system, which includes the brain and spinal cord. According to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5) published in 2013, these conditions generally appear in early childhood, usually before children start school, and can persist into adulthood. The key characteristic of all these disorders is that they negatively impact a person's functioning in one or more domains of life depending on the disorder and deficits it has caused. All of these disorders and their levels of impairment exist on a spectrum, and affected individuals can experience varying degrees of symptoms and deficits, despite having the same diagnosis.

<span class="mw-page-title-main">Heritability of autism</span> The rate at which autism is inherited

The heritability of autism is the proportion of differences in expression of autism that can be explained by genetic variation; if the heritability of a condition is high, then the condition is considered to be primarily genetic. Autism has a strong genetic basis. Although the genetics of autism are complex, autism spectrum disorder (ASD) is explained more by multigene effects than by rare mutations with large effects.

<span class="mw-page-title-main">Causes of autism</span> Proposed causes of autism

Many causes of autism, including environmental and genetic factors, have been recognized or proposed, but understanding of the theory of causation of autism is incomplete. Attempts have been made to incorporate the known genetic and environmental causes into a comprehensive causative framework. ASD is a neurodevelopmental disorder marked by impairments in communicative ability and social interaction, as well as restricted and repetitive behaviors, interests, or activities not suitable for the individual's developmental stage. The severity of symptoms and functional impairment vary between individuals.

The epidemiology of autism is the study of the incidence and distribution of autism spectrum disorders (ASD). A 2022 systematic review of global prevalence of autism spectrum disorders found a median prevalence of 1% in children in studies published from 2012 to 2021, with a trend of increasing prevalence over time. However, the study's 1% figure may reflect an underestimate of prevalence in low- and middle-income countries.

<span class="mw-page-title-main">22q13 deletion syndrome</span> Rare genetic syndrome

22q13 deletion syndrome, known as Phelan–McDermid syndrome (PMS), is a genetic disorder caused by deletions or rearrangements on the q terminal end of chromosome 22. Any abnormal genetic variation in the q13 region that presents with significant manifestations (phenotype) typical of a terminal deletion may be diagnosed as 22q13 deletion syndrome. There is disagreement among researchers as to the exact definition of 22q13 deletion syndrome. The Developmental Synaptopathies Consortium defines PMS as being caused by SHANK3 mutations, a definition that appears to exclude terminal deletions. The requirement to include SHANK3 in the definition is supported by many but not by those who first described 22q13 deletion syndrome.

<span class="mw-page-title-main">Neurogenomics</span> Part of the study of the genome

Neurogenomics is the study of how the genome of an organism influences the development and function of its nervous system. This field intends to unite functional genomics and neurobiology in order to understand the nervous system as a whole from a genomic perspective.

Autism, also called autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by symptoms of deficient reciprocal social communication and the presence of restricted, repetitive, and inflexible patterns of behavior. Autism generally affects a person's ability to understand and connect with others, as well as their adaptability to everyday situations, with its severity and support needs varying widely across the underlying spectrum. For example, some are nonverbal, while others have proficient spoken language.

<span class="mw-page-title-main">Imprinted brain hypothesis</span> Conjecture on the causes of autism and psychosis

The imprinted brain hypothesis is an unsubstantiated hypothesis in evolutionary psychology regarding the causes of autism spectrum and schizophrenia spectrum disorders, first presented by Bernard Crespi and Christopher Badcock in 2008. It claims that certain autistic and schizotypal traits are opposites, and that this implies the etiology of the two conditions must be at odds.

Cognitive genomics is the sub-field of genomics pertaining to cognitive function in which the genes and non-coding sequences of an organism's genome related to the health and activity of the brain are studied. By applying comparative genomics, the genomes of multiple species are compared in order to identify genetic and phenotypical differences between species. Observed phenotypical characteristics related to the neurological function include behavior, personality, neuroanatomy, and neuropathology. The theory behind cognitive genomics is based on elements of genetics, evolutionary biology, molecular biology, cognitive psychology, behavioral psychology, and neurophysiology.

Autism spectrum disorder (ASD) refers to a variety of conditions typically identified by challenges with social skills, communication, speech, and repetitive sensory-motor behaviors. The 11th International Classification of Diseases (ICD-11), released in January 2021, characterizes ASD by the associated deficits in the ability to initiate and sustain two-way social communication and restricted or repetitive behavior unusual for the individual's age or situation. Although linked with early childhood, the symptoms can appear later as well. Symptoms can be detected before the age of two and experienced practitioners can give a reliable diagnosis by that age. However, official diagnosis may not occur until much older, even well into adulthood. There is a large degree of variation in how much support a person with ASD needs in day-to-day life. This can be classified by a further diagnosis of ASD level 1, level 2, or level 3. Of these, ASD level 3 describes people requiring very substantial support and who experience more severe symptoms. ASD-related deficits in nonverbal and verbal social skills can result in impediments in personal, family, social, educational, and occupational situations. This disorder tends to have a strong correlation with genetics along with other factors. More research is identifying ways in which epigenetics is linked to autism. Epigenetics generally refers to the ways in which chromatin structure is altered to affect gene expression. Mechanisms such as cytosine regulation and post-translational modifications of histones. Of the 215 genes contributing, to some extent in ASD, 42 have been found to be involved in epigenetic modification of gene expression. Some examples of ASD signs are specific or repeated behaviors, enhanced sensitivity to materials, being upset by changes in routine, appearing to show reduced interest in others, avoiding eye contact and limitations in social situations, as well as verbal communication. When social interaction becomes more important, some whose condition might have been overlooked suffer social and other exclusion and are more likely to have coexisting mental and physical conditions. Long-term problems include difficulties in daily living such as managing schedules, hypersensitivities, initiating and sustaining relationships, and maintaining jobs.

Dup15q syndrome is the common name for maternally inherited chromosome 15q11.2-q13.1 duplication syndrome. This is a genomic copy number variant that leads to a type of neurodevelopmental disorder, caused by partial duplication of the proximal long arm of Chromosome 15. This variant confers a strong risk for autism spectrum disorder, epilepsy, and intellectual disability. It is the most common genetic cause of autism, accounting for approximately 1-3% of cases. Dup15q syndrome includes both interstitial duplications and isodicentric duplications of 15q11.2-13.1.

Joseph D. Buxbaum is an American molecular and cellular neuroscientist, autism researcher, and the Director of the Seaver Autism Center at the Icahn School of Medicine at Mount Sinai. Buxbaum is also, along with Simon Baron-Cohen, the co-editor of the BioMed Central journal Molecular Autism, and is a member of the scientific advisory board of the Autism Science Foundation. Buxbaum is a Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences. He is also the Vice Chair for Research and for Mentoring in the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai.

The development of an animal model of autism is one approach researchers use to study potential causes of autism. Given the complexity of autism and its etiology, researchers often focus only on single features of autism when using animal models.

Sex and gender differences in autism exist regarding prevalence, presentation, and diagnosis.

Wendy K. Chung is an American clinical and molecular geneticist and physician. She is the Chair of the Department of Pediatrics at Boston Children's Hospital and is on the faculty at Harvard Medical School. She is the author of 700 peer-reviewed articles and 75 chapters and has won several awards as a physician, researcher, and professor. Chung helped to initiate a new form of newborn screening for spinal muscular atrophy which is used nationally and was among the plaintiffs in the Supreme Court case which banned gene patenting.

ADNP syndrome, also known as Helsmoortel-Van der Aa syndrome (HVDAS), is a non-inherited neurodevelopmental disorder caused by mutations in the activity-dependent neuroprotector homeobox (ADNP) gene.

John N. Constantino is a child psychiatrist and expert on neurodevelopmental disorders, especially autism spectrum disorders (ASD). Constantino is the inaugural System Chief of Behavioral and Mental Health at Children's Healthcare of Atlanta. He is a Professor of Pediatrics, Psychiatry and Behavioral Sciences and Genetics at the Emory University School of Medicine.

Marian Diamond Sigman (1941–2012) was a developmental and child clinical psychologist known for her research on autism spectrum disorder (ASD). At the time of her death, she was Professor Emeritus of Psychiatry and Biobehavioral Sciences and Psychology at the University of California, Los Angeles (UCLA).

Sagiv Shifman is an Israeli scientist, professor in the field of neurogenetics at the Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem. He holds the Arnold and Bess Zeldich Ungerman chair in Neurobiology.

References

  1. ↑ "Daniel Geschwind". NAM Member Profiles.
  2. ↑ Winden, Kellen D.; Oldham, Michael C.; Mirnics, Karoly; Ebert, Philip J.; Swan, Christo H.; Levitt, Pat; Rubenstein, John L.; Horvath, Steve; Geschwind, Daniel H. (2009). "The organization of the transcriptional network in specific neuronal classes". Molecular Systems Biology. 5: 291. doi:10.1038/msb.2009.46. ISSN   1744-4292. PMC   2724976 . PMID   19638972.
  3. ↑ Oldham, Michael C.; Horvath, Steve; Geschwind, Daniel H. (2006-11-21). "Conservation and evolution of gene coexpression networks in human and chimpanzee brains". Proceedings of the National Academy of Sciences of the United States of America. 103 (47): 17973–17978. Bibcode:2006PNAS..10317973O. doi: 10.1073/pnas.0605938103 . ISSN   0027-8424. PMC   1693857 . PMID   17101986.
  4. ↑ Oldham, Michael C.; Konopka, Genevieve; Iwamoto, Kazuya; Langfelder, Peter; Kato, Tadafumi; Horvath, Steve; Geschwind, Daniel H. (November 2008). "Functional organization of the transcriptome in human brain". Nature Neuroscience. 11 (11): 1271–1282. doi:10.1038/nn.2207. ISSN   1546-1726. PMC   2756411 . PMID   18849986.
  5. ↑ Gandal, Michael J.; Zhang, Pan; Hadjimichael, Evi; Walker, Rebecca L.; Chen, Chao; Liu, Shuang; Won, Hyejung; van Bakel, Harm; Varghese, Merina; Wang, Yongjun; Shieh, Annie W.; Haney, Jillian; Parhami, Sepideh; Belmont, Judson; Kim, Minsoo (2018-12-14). "Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder". Science. 362 (6420): eaat8127. Bibcode:2018Sci...362.8127G. doi:10.1126/science.aat8127. ISSN   1095-9203. PMC   6443102 . PMID   30545856.
  6. ↑ Parikshak, Neelroop N.; Swarup, Vivek; Belgard, T. Grant; Irimia, Manuel; Ramaswami, Gokul; Gandal, Michael J.; Hartl, Christopher; Leppa, Virpi; Ubieta, Luis de la Torre; Huang, Jerry; Lowe, Jennifer K.; Blencowe, Benjamin J.; Horvath, Steve; Geschwind, Daniel H. (2016-12-15). "Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism". Nature. 540 (7633): 423–427. Bibcode:2016Natur.540..423P. doi:10.1038/nature20612. ISSN   1476-4687. PMC   7102905 . PMID   27919067.
  7. ↑ Voineagu, Irina; Wang, Xinchen; Johnston, Patrick; Lowe, Jennifer K.; Tian, Yuan; Horvath, Steve; Mill, Jonathan; Cantor, Rita M.; Blencowe, Benjamin J.; Geschwind, Daniel H. (2011-05-25). "Transcriptomic analysis of autistic brain reveals convergent molecular pathology". Nature. 474 (7351): 380–384. doi:10.1038/nature10110. ISSN   1476-4687. PMC   3607626 . PMID   21614001.
  8. 1 2 "Daniel Geschwind: After many detours, on the trail of autism's genetics". The Transmitter: Neuroscience News and Perspectives. 2009-02-17. Retrieved 2024-08-08.
  9. 1 2 "Dr. Daniel Geschwind Receives 2012 Ruane Prize for Outstanding Achievement in Autism Research". Dr. Daniel Geschwind Receives 2012 Ruane Prize for Outstanding Achievement in Autism Research | Brain & Behavior Research Foundation. 2012-11-07. Retrieved 2024-08-08.
  10. 1 2 3 4 5 Lewis, Talia (15 September 2022). "Daniel H. Geschwind Receives National Academy of Medicine's Sarnat Prize for Contributions to Understanding of the Genetics of Autism". National Academy of Medicine (Press release). Retrieved 22 September 2022.
  11. 1 2 3 "Daniel H. Geschwind". UCLA Website. Retrieved 12 February 2018.
  12. 1 2 3 4 "Daniel Geschwind". Allen Institute for Brain Science. Archived from the original on 10 December 2014. Retrieved 5 December 2014.
  13. ↑ "Daniel H. Geschwind". UCLA Newsroom. Retrieved 17 May 2016.
  14. ↑ "Daniel Geschwind – UCLA Graduate Programs in Bioscience (GPB)" . Retrieved 2024-08-08.
  15. ↑ "Alumni". The Geschwind Lab at UCLA. 2023-04-05. Retrieved 2024-08-08.
  16. ↑ "Dan Geschwind". scholar.google.com. Retrieved 2024-08-08.
  17. ↑ "Highly Cited Researchers List 2017 - Top Researchers Around the World". clarivate.com. Retrieved 8 October 2018.
  18. ↑ "Geschwind". geschwindlab.dgsom.ucla.edu. Retrieved 8 October 2018.
  19. ↑ "The Geschwind Lab". geschwindlab.dgsom.ucla.edu. Retrieved 8 October 2018.
  20. ↑ "Daniel Geschwind, MD, PhD". UCLA Med School. 2022-02-27. Retrieved 2024-08-08.
  21. ↑ Geschwind, Daniel H.; Sowinski, Janice; Lord, Catherine; Iversen, Portia; Shestack, Jonathan; Jones, Patrick; Ducat, Lee; Spence, Sarah J. (August 2001). "The Autism Genetic Resource Exchange: A Resource for the Study of Autism and Related Neuropsychiatric Conditions". American Journal of Human Genetics. 69 (2): 463–466. doi:10.1086/321292. ISSN   0002-9297. PMC   1235320 . PMID   11452364.
  22. ↑ "Brains of people with autism spectrum disorder share similar molecular abnormalities". UCLA. Retrieved 2024-10-21.
  23. ↑ Wolman, David (2006). A Left Hand Turn Around the World. Da Capo Press. p. 195. ISBN   9780786734979.
  24. ↑ Geschwind, Michael D. (29 May 2010). "Are you Related to "the Geschwind?"". Neuropsychology Review. 20 (2): 123–125. doi:10.1007/s11065-010-9135-9. ISSN   1040-7308. PMC   2881317 . PMID   20512417.
  25. ↑ Duran, Janice. "Decoding the Brain: Insights into Neuropsychiatric Disorders".
  26. ↑ "Daniel Geschwind, M.D., Ph.D. – UCLA Brain Research Institute (BRI)" . Retrieved 2024-08-08.
  27. ↑ "Society of Biological Psychiatry Gold Medal Award | Society of Biological Psychiatry" . Retrieved 2024-08-08.
  28. ↑ "Distinguished Investigators". Allen Institute. Retrieved 2024-08-08.
  29. ↑ "Daniel H. Geschwind, MD - Neurodevelopmental Disorders". www.uclahealth.org. Retrieved 2024-08-08.
  30. ↑ "Daniel Geschwind | UCLA Profiles". profiles.ucla.edu. Retrieved 2024-08-08.
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