Matthew Anderson Lab

About the Lab

Research Projects

Molecular-Circuit Mechanisms and Therapeutics for Immune and Genetic Autisms

• 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)
• Molecular pathway overlap of sporadic (immune) autism and genetic autisms
• Sociability Circuits: 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)
• Aggression/Irritability Circuits: 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).

Molecular Mechanisms and Therapeutics for Central and Peripheral Axonal Diseases

• Genetic neurodevelopmental disease resulting from MAPK8IP3 truncations and missense mutations

Cystic Fibrosis

• Anderson MP, Gregory RJ, Thompson S, Souza DW, Paul S, Mulligan RC, Smith AE, Welsh MJ. Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. Science. 1991; 253(5016):202-5. PMID: 1712984
• Anderson MP, Rich DP, Gregory RJ, Smith AE, Welsh MJ. Generation of cAMP-activated chloride currents by expression of CFTR. Science 1991; 251(4994):679-82. PMID: 1704151
• Anderson MP, Berger HA, Rich DP, Gregory RJ, Smith AE, Welsh MJ. Nucleoside triphosphates are required to open the CFTR chloride channel. Cell. 1991; 67(4):775-84. PMID: 1718606
• Anderson MP, Welsh MJ. Regulation by ATP and ADP of CFTR chloride channels that contain mutant nucleotide-binding domains. Science. 1992; 257(5077):1701-4. PMID: 1382316

Human Brain Evolution Molecular Mechanisms

• 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).

Identify, Resolve Molecular-Circuit Mechanisms, and Develop Therapeutics for Unrecognized CD8 T-Cell-Based Behavioral Brain Diseases

• CD8 cytotoxic T-cell immunity targeting hypothalamic feeding circuits in obesity (~40% of cases) (Ahrendsen et al. Acta. Neuropath. Comm. 2023)
• CD8 cytotoxic T-cell immunity targeting astrocyte glia limitans in autism (~65% of cases). (DiStasio et al. Ann. Neurol. 2019)

Matthew P. Anderson, MD, PhD

Harrington Investigator; Professor, Department of Pathology, School of Medicine at Case Western Reserve University; Co-Director, Oxford-Harrington Rare Disease Centre; Visiting Professor, University of Oxford

Curriculum Vitae