Matthew Anderson, MD, PhD

Matthew P. Anderson, MD, PhD, is co-Director of The Oxford-Harrington Rare Disease Centre (‘OHC’), a partnership between the University of Oxford, UK and Harrington Discovery Institute at University Hospitals, Cleveland, Ohio, aimed at driving cutting-edge rare disease breakthroughs. Dr. Anderson is also an Investigator, Harrington Discovery Institute and Professor, Department of Pathology at University Hospitals and Case Western Reserve University.
Dr. Anderson brings a wealth of scientific and clinical research and translational medicine experiences to his role at the OHC from a distinguished career in academia and industry. Prior to joining the OHC, he served as Vice President of Research and Preclinical Development, and Head of the Neuroscience Therapeutic Focus Area leading a team of 45 scientists and physician drug developers at Regeneron Pharmaceuticals, Inc., a Fortune 500 company. For many year, Dr. Anderson served as Chief of the Neuropathology Division at Beth Israel Deaconess Medical Center at Harvard Medical School (Boston, MA), running a biomedical research program yielding breakthroughs in neurological, neuropsychiatric, and neurodevelopmental diseases including epilepsy and autism.
Dr. Anderson received MD and PhD degrees from the University of Iowa College of Medicine. For his PhD in Physiology and Biophysics, working under the mentorship of Dr. Michael Welsh, a preeminent physician scientist, Dr. Anderson produced seminal studies on the function of the CFTR chloride channel that is mutated in cystic fibrosis awarded the International Distinguished Dissertation Award (awarded every 5 years to the top science). These studies were foundational to the subsequent small molecule therapeutics that saved lives for individuals with Cystic Fibrosis. Subsequently, he completed postdoctoral research training at Massachusetts Institute of Technology (MIT), under the mentorship of Nobel Laureate Dr. Susumu Tonegawa developing expertise in mouse genetic engineering, brain circuit electrophysiology, and behavioral circuits studies that contributed our understanding of epilepsy and sleep regulation. Dr. Anderson uses these advanced genetic engineering and molecular biology technologies formerly at Harvard and now at the Harrington Discovery Institute/Oxford to study brain disease mechanisms and therapeutics.
Dr. Anderson’s laboratory at Harvard has made a series of seminal discoveries: 

1.  CD8 cytotoxic T-cell immunity targeting astrocyte glia limitans in autism (~65% of cases). (DiStasio et al. Ann. Neurol. 2019)
2. CD8 cytotoxic T-cell immunity targeting hypothalamic feeding circuits in obesity (~40% of cases) – a brain disease research program aimed at revealing CD8 T-cells target behavioral circuits in wide range of psychiatric disease (Ahrendsen et al. Acta. Neuropath. Comm. 2023)
3. Augmented glutamatergic excitatory synaptic transmission underlies a genetic epilepsy due to truncating mutations in synapse organizer LGI1 (Zhou et al. Nat. Med. 2009; Boillot et al. Brain 2014). 
4. UBE3A underlies a genetic autism due to idic15/dup15q acting in the nucleus to cause behavioral symptoms and converging and synergizing with epilepsy to repress expression of synapse organizer CBLN1 to break autism gene-rich NRXN1-CBLN1-GRID1 transsynaptic complex (Smith et al. Sci. Trans. Med. 2011; Krishnan et al. Nature 2017; Nong et al. bioRxiv 2023)
5. Ventral tegmental area (VTA) glutamatergic neurons drive social behavior where UBE3A reduces CBLN1 to breaks glutamatergic synapse and impair sociability (Smith et al. Sci. Trans. Med. 2011; Krishnan et al. Nature 2017)
6. Hypothalamic feedback inhibitory arcuate AgRP/NPY neurons inhibit irritability/aggression where UBE3A reduces CBLN1 to break a collateral glutamatergic synapses from aggression driving ventromedial hypothalamic neurons in the ventrolateral subdivision to arcuate AgRP/NPY neurons that provide feedback inhibition (Nong et al. bioRxiv 2023).
7. Human-specific SINE-VNTR-ALU (SVA) retrotransposon in microcephaly gene CDK5RAP2 intron represses its expression to slow progenitor to neuron maturation, potentially contributing to the slowed maturation, enlarged brain, and advanced cognitive and sensorimotor functions in human relative to their closest living relative the chimpanzee. Discovered the function of founding SVA-lncRNA gene family member, AK057321, a gene duplicated in rare cases of autism. It forms RNA:DNA heteroduplexes with genomic SVA sequences and decoy binds SVA repressive KRAB domain zinc finger transcription factor ZNF91 to release the CDK5RAP2 gene repression. SVA retrotransposon and SVA-lncRNA gene regulatory system regulates human genes underlying intellectual, social, and language abilities providing new insights into the genetic basis of human evolution. (Nadler et al. Commun. Biol. 2023).