Anthony Wynshaw-Boris, MD, PhD

Department of Genetics and Genome Sciences
School of Medicine
James H. Jewell MD ’34 Professor of Genetics
Department of Genetics and Genome Sciences
School of Medicine
Department of Neurosciences
School of Medicine
Department of Pediatrics
School of Medicine
Cancer Genomics and Epigenomics Program
Case Comprehensive Cancer Center

Tony Wynshaw-Boris, MD, PhD, is a physician scientist whose laboratory studies the pathophysiological mechanisms of human neurogenetic disorders, using animal models and more recently inducible pluripotent stem cell (iPSC) models. His studies have led to important insights into the pathophysiology of many of these disorders, and in some cases, novel therapies.

Dr. Wynshaw-Boris received his MD/PhD degrees from Case Western Reserve University School of Medicine. His PhD was under the direction of Richard Hanson, PhD, where he elucidated the sequences within the PEPCK promoter required for activation by cAMP and glucocorticoids. He did his residency in Pediatrics at Rainbow Babies and Children's Hospital, followed by a medical genetics fellowship at Boston Children's Hospital. While in Boston, he did a postdoctoral fellowship at Harvard Medical School under the direction of Philip Leder, MD, where he studied mouse models of developmental disorders.

In 1994, Dr. Wynshaw-Boris set up an independent laboratory at the National Human Genome Research Institute of the NIH, where he initiated a program using mouse models to study human genetic diseases, with a focus on neurogenetic diseases. In 1999, he moved to UCSD School of Medicine, where he became Professor of Pediatrics and Medicine, as well as Chief of the Division of Medical Genetics in the Department of Pediatrics. In 2007, he moved to UCSF School of Medicine, where he was the Charles J. Epstein Professor of Human Genetics and Pediatrics, and the Chief of the Division of Medical Genetics in the Department of Pediatrics. In June 2013, he returned to Cleveland to become the Chair of the Department of Genetics and Genome Sciences. He stepped down as Chair in July 2023 to focus on his research. 

Besides his broad experience in the study of genetic disorders as a scientist, Dr. Wynshaw-Boris is an ACMGG Board Certified medical geneticist. He was the Executive Editor of Human Molecular Genetics (Oxford University Press) for 15 years. He is committed to training researchers and physician scientists. In his laboratory he has trained more than 40 graduate students and postdoctoral fellows over the last 30 years, and was also the PI of two different training grants.  

Dr. Wynshaw-Boris was President of the American Society for Human Genetics for 2020. He has served on the ASHG Nominating Committee (2001), the ASHG Program Committee (2002-2005, Chair for 2005), was the Chair of the ASHG Selection Committee, MD/PhD Student Travel Awards (2004), was a Director of ASHG (2007-2009), and a member of the 12th International Congress of Human Genetics Program Committee (2009-2011). He was the Executive Editor of Human Molecular Genetics from 2005-2021. He was appointed to the National Advisory Child Health and Human Development Council of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, in 2019. He has also been elected to membership in the American Society for Clinical Investigation (2002), the Association of American Physicians (2007), the American Pediatric Society (2008), and he was elected as Fellow of the American Association for the Advancement of Science (2012).

Research Information

Research Interests

Dr. Wynshaw-Boris’s laboratory has published more than 180 peer-reviewed articles in scientific journals, and numerous review articles. His laboratory continues to use mouse and iPSC models to shed light on mechanisms of neurogenetic diseases with the goal of providing novel therapies. They determined components of the major pathways through which genes responsible for ataxia-telangiectasia and the neuronal migration defect lissencephaly act and identified novel potential therapeutic targets. For example, his laboratory demonstrated that Lis1 mutant mice display dosage-dependent neuronal migration defects (Hirotsune et al. Nature Genet 1998; 19:333-339) and established a novel role for LIS1 during neurogenesis and mitosis by regulating spindle orientation and microtubule capture (Yingling et al. Cell 2008; 132, 474-486). Wynshaw-Boris was the first to produce mice with mutations in all three Dishevelled genes and defined single, double, and triple mutant phenotypes that model complex disease (Ngo et al. Dev Biol 2020; 464:161-175).  Dvl1 mutant mice were the first found to display mammalian social behavior defects (Lijam et al. Cell 1997; 90:895-905), and became models for human neuropsychiatric diseases, including autism, revealing a novel transcriptional cascade regulating embryonic neurogenesis and adult social behavior that is conserved in iPSC models of autism.  His laboratory also discovered that during reprogramming into iPSCs, ring chromosomes are lost and replaced by duplication of a normal chromosome, providing potential “chromosome therapy” for chromosomal defects (Bershteyn et al. Nature 2014;507:99-103). 

Research Projects

Autism and Early Brain Overgrowth

A long-standing research interest in the Wynshaw-Boris laboratory is autism spectrum disorder (ASD). Over the last several years, it is apparent that ASD, a highly heritable disorder, appears to be associated with brain overgrowth in about 20% of ASD individuals, although the precise timing and cause of this overgrowth is unknown. They are examining variations in genes and pathways important for neurogenesis, mitosis, and apoptosis in autism. These pathways directly tie in with their studies of mouse Dishevelled pathways and pathways important neuronal migration. Of note, they have found a novel cortical abnormality in postmortem studies of young autistic individuals that may be fundamental to the development of autism. A recent publication found unique abnormalities in gene expression from dorsolateral prefrontal cortex of young autistic patients relative to typically developing children. They have made iPS cells from autism patients who displayed early brain overgrowth and control, non-autistic individuals with normal brain size to see if there are cellular phenotypes associated with early brain overgrowth. Notably, they found that neural progenitor cells from ASD individuals with early brain overgrowth display increased proliferation compared with neural progenitor cells from control individuals (Marchetto et al. Mol Psychiatry 2017; 22: 820. PMID: 27378147). They have used both cerebral and cerebellar organoids to model human brain development and neurogenetic disorders, including lissencephaly (Bershteyn et al. Cell Stem Cell 2017; 20: 435. PMID: 28111201), ASD resulting from early brain overgrowth (Fu et al. Am J Human Genet 2023; 110: 826. PMID: 37098352), and most recently developed a novel lineage tracing method to study neurogenesis (Bury et al. bioRxiv 2023 Jun 17:2023.06.17.545314. doi: 10.1101/2023.06.17.545314. Preprint. PMID: 37398102). These studies have facilitated the investigation of mechanisms of early brain development. As an example, we found that two iPSC models with ASD and early brain overgrowth were found to have variants in PTEN or CTNNB1, coding for beta-catenin. Isogenic lines with the PTEN variant were used to uncover effects of the variant and the ASD genetic background on neurogenesis (Fu et al. Am J Human Genet 2023; 110: 826. PMID: 37098352), defining common pathways important for cellular phenotypes, while the isogenic lines were used in the lineage tracing studies (Bury et al. bioRxiv 2023 Jun 17:2023.06.17.545314. doi: 10.1101/2023.06.17.545314. Preprint. PMID: 37398102).

Collaborative Projects: Use of Brain Organoids to Investigate HIV Latency and Drugs of Abuse

The ability to produce organoids that recapitulate human cortical brain development using brain organoids has allowed the Wynshaw-Boris laboratory to establish collaborations to investigate important questions in other areas. They have established two such collaborations. 

In collaboration with Dr. Jonathan Karn, the Wynshaw-Boris laboratory will use expertise to continue to advance organoid models of HIV latency in microglial cells for the studies outlined in this proposal.

In collaboration with Dr. Alan Levine, the Wynshaw-Boris laboratory will use brain organoid models to characterize the biological outcome, signaling pathway, and the synergistic mechanism of action of fentanyl, methamphetamine, and novel thiolester opioid antagonists.