About

Michael Byrne Robinson, Ph.D., is an Emeritus Professor of Pediatrics specializing in Developmental and Behavioral Pediatrics at the University of Pennsylvania Medical School. He is a member of the Institute for Neurological Sciences and serves as the Director of the Analytical Neurochemistry Core at the Intellectual and Developmental Disabilities Research Center (IDDRC). Additionally, he is a member of the Children's Hospital of Philadelphia Research Institute and heads the Neuroscience Affinity Group there. His research focuses on signaling pathways that regulate glutamate transporters and their relationship to acute brain injury. His laboratory investigates the normal physiology of excitatory amino acids (EAAs) such as glutamate and aspartate, which are the primary excitatory neurotransmitters in the mammalian central nervous system. These neurotransmitters, while essential for rapid depolarization, can also be neurotoxic when their extracellular levels are excessively elevated, contributing to neurodegeneration after CNS insults like stroke and head trauma. Dr. Robinson's work emphasizes understanding the regulation of extracellular glutamate and aspartate levels, which are normally maintained by sodium-dependent high-affinity transporters on neurons and glial cells. His research employs biochemical, cell biological, and molecular biological techniques to explore transporter regulation, including cell culture, transfection, assays for signaling pathway activation, and transporter activity measurement. His long-term goal is to develop strategies to limit glutamate-mediated damage by elucidating endogenous mechanisms that clear this excitotoxin, thereby advancing neuroprotective approaches.

Research topics

• Biology
• Cell biology
• Chemistry
• Neuroscience
• Biochemistry

Selected publications

• Identification of a Subpopulation of Astrocyte Progenitor Cells in the Neonatal Subventricular Zone: Evidence that Migration is Regulated by Glutamate Signaling

  Neurochemical Research · 2025-01-09 · 1 citations

  articleOpen accessSenior author

  Abstract In mice engineered to express enhanced green fluorescent protein (eGFP) under the control of the entire glutamate transporter 1 (GLT1) gene, eGFP is found in all ‘adult’ cortical astrocytes. However, when 8.3 kilobases of the human GLT1/EAAT2 promoter is used to control expression of tdTomato (tdT), tdT is only found in a subpopulation of these eGFP-expressing astrocytes. The eGFP mice have been used to define mechanisms of transcriptional regulation using astrocytes cultured from cortex of 1–3 day old mice. Using the same cultures, we were never able to induce tdT + expression. We hypothesized that these cells might not have migrated into the cortex by this age. In this study, we characterized the ontogeny of tdT + cells, performed single-cell RNA sequencing (scRNA-seq), and tracked their migration in organotypic slice cultures. At postnatal day (PND) 1, tdT + cells were observed in the subventricular zone and striatum but not in the cortex, and they did not express eGFP. At PND7, tdT + cells begin to appear in the cortex with their numbers increasing with age. At PND1, scRNA-seq demonstrates that the tdT + cells are molecularly heterogeneous, with a subpopulation expressing astrocytic markers, subsequently validated with immunofluorescence. In organotypic slices, tdT + cells migrate into the cortex, and after 7 days they express GLT1, NF1A, and eGFP. An ionotropic glutamate receptor (iGluR) antagonist reduced by 50% the distance tdT + cells migrate from the subventricular zone into the cortex. The pan-glutamate transport inhibitor, TFB-TBOA, increased, by sixfold, the number of tdT + cells in the cortex. In conclusion, although tdT is expressed by non-glial cells at PND1, it is also expressed by glial progenitors that migrate into the cortex postnatally. Using this fluorescent labeling, we provide novel evidence that glutamate signaling contributes to the control of glial precursor migration.

  PublisherOA PDFDOI

• Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer

  UNC Libraries · 2024-03-12

  articleOpen access

  Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.

  PublisherDOI

• Brain energy metabolism: A roadmap for future research

  Journal of Neurochemistry · 2024-01-06 · 90 citations

  reviewOpen access

  Abstract Although we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major brain substrates and associated transporters, the roles of insulin and of lipid droplets, the emerging role of metabolism in microglia, mysteries about the major brain cofactor and signaling molecule NAD + , as well as unsolved problems underlying brain metabolism in pathologies such as traumatic brain injury, epilepsy, and metabolic downregulation during hibernation. It describes our current level of understanding of these facets of brain energy metabolism as well as a roadmap for future research. image

  PublisherOA PDFDOI

• The nutritional profile of plant-based meat alternatives vs. traditional plant proteins: A product audit

  Proceedings of The Nutrition Society · 2024-11-01 · 1 citations

  articleOpen access

  Plant-based meat alternatives (PBMAs) are products made from manufactured ingredients such as protein isolates, to replicate the organoleptic and functional properties of meat (1) . Traditional plant proteins (TPPs) such as tofu, tempeh and legume-based dishes are whole plant foods and have been longstanding components of the protein group of food-based dietary guidelines (FBDGs) (2) . PBMAs have been added to some recently revised FBDGs (3,4) , however, with considerable differences in ingredient composition, the objective of this study was to evaluate if these products are similar in terms of energy and macronutrients content. An online audit of PBMAs available in Tesco and Sainsbury’s was completed (November 2023January 2024). On-pack information was extracted, and similar products were grouped. Within eligible categories (burgers, beef-style dishes and seafood), products were further grouped according to their classification as a PBMA or TPP. Categories such as tofu and tempeh were combined and compared with PBMA chicken fillets/chunks and beef/pork products separately. Mean energy and nutrient contents were compared using independent sample t-tests, with P values ≤ 0.05 considered statistically significant. A-scores from the UK’s Nutrient Profiling Model (5) were calculated and the EU threshold for protein claims (≥12% energy from protein) (6) was applied to determine the proportion of products within each category considered a protein source. Within the burger category, PBMAs (n = 43) had a significantly higher mean energy (206.8 vs. 197.4 kcal/100g, P = 0.008), total fat (11.2 vs. 8.4 g/100g, P = 0.05), and saturated fat content (2.5 vs. 0.8 g/100g, P = 0.02), and significantly lower carbohydrate content (10.4 vs. 23.5 g/100g, P = 0.002) than TPPs (n = 14). Within the seafood category, PBMAs (n = 11) had a significantly lower total fat content (9.9 vs. 11.4 g/100g, P = 0.001) and significantly higher protein (6.6 vs. 4.5 g/100g, P = 0.04) and salt content (1.0 vs. 0.8 g/100g, P = 0.03) than TPPs (n = 5). PBMAs within the beef-style dishes category (n = 19) were significantly higher in energy (174.2 vs. 111.5 kcal/100g, P = 0.003) than TPPs (n = 20). When PBMA chicken (n = 81) and beef/pork (n = 20) were compared with tofu, tempeh and jackfruit (n = 17 and 20 respectively), PBMA chicken had a significantly higher carbohydrate content (12.2 vs. 2.6 g/100g, P<0.001) and PBMA beef/pork had a significantly higher protein content (17.2 vs. 13.1 g/100g, P = 0.005). PBMAs had higher mean A-scores (6.4 - 8.5) than TPPs (3.2 - 6.6) in 4/5 categories indicating they are ‘less healthy.’ Very few TPPs within the burger and seafood categories met the protein threshold compared to PBMAs. Differences in energy, macronutrient content and A-scores, mean PBMAs and TPPs cannot be considered nutritionally equal.

  PublisherOA PDFDOI

• Evaluation of the performance of next generation sequencing ABO probes in a solid organ transplant population

  Human Immunology · 2024-09-01

  article
  PublisherDOI

• Astrocytic <scp>PAR1</scp> and <scp>mGluR2/3</scp> control synaptic glutamate time course at hippocampal <scp>CA1</scp> synapses

  Glia · 2024-06-12 · 4 citations

  articleOpen access

  Astrocytes play an essential role in regulating synaptic transmission. This study describes a novel form of modulation of excitatory synaptic transmission in the mouse hippocampus by astrocytic G-protein-coupled receptors (GPCRs). We have previously described astrocytic glutamate release via protease-activated receptor-1 (PAR1) activation, although the regulatory mechanisms for this are complex. Through electrophysiological analysis and modeling, we discovered that PAR1 activation consistently increases the concentration and duration of glutamate in the synaptic cleft. This effect was not due to changes in the presynaptic glutamate release or alteration in glutamate transporter expression. However, blocking group II metabotropic glutamate receptors (mGluR2/3) abolished PAR1-mediated regulation of synaptic glutamate concentration, suggesting a role for this GPCR in mediating the effects of PAR1 activation on glutamate release. Furthermore, activation of mGluR2/3 causes glutamate release through the TREK-1 channel in hippocampal astrocytes. These data show that astrocytic GPCRs engage in a novel regulatory mechanism to shape the time course of synaptically-released glutamate in excitatory synapses of the hippocampus.

  PublisherOA PDFDOI

• Appendix B. Employer's Claims

  2023-01-06

  otherOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Issue Information

  European Journal Of Haematology · 2023-08-04

  paratextOpen access

  Impact of 1q gains on treatment outcomes of patients with newly diagnosed multiple myeloma in a

  PublisherOA PDFDOI

• Author response for "Brain energy metabolism: A roadmap for future research"

  2023-11-29 · 1 citations

  peer-review
  PublisherDOI

• Glutamatergic neurotransmission

  Elsevier eBooks · 2023-01-01

  book-chapterSenior author
  PublisherDOI

Recent grants

• Analytical Neurochemistry: Core D

  NIH · $12.7M · 2021

• NIH Grant R01HD060132

  NIH · $1.7M · 2014

• Regulation of glutamate transport in astrocyte subtypes and in ALS

  NIH · $2.3M · 2015–2021

• Astroglial Glutamate Transporters, Calcium, and Mitochondria

  NIH · $546k · 2012–2018

• NIH Grant R01NS039011

  NIH · $2.6M · 2010

Frequent coauthors

• Elizabeth N. Krizman

  Children's Hospital of Philadelphia

  103 shared

• Mark L. Batshaw

  Children's National

  54 shared

• Marco I. González

  University of California, Davis

  53 shared

• Joshua G. Jackson

  53 shared

• Jeffrey D. Rothstein

  Johns Hopkins University

  47 shared

• Olga Zelenaia

  46 shared

• Zila Martínez‐Lozada

  Children's Hospital of Philadelphia

  44 shared

• T. J. Rathz

  University of Alabama in Huntsville

  43 shared

Education

• Postdoctoral Fellow

  Johns Hopkins University

  1988

• PhD, Biochemistry

  University of Minnesota System

  1985

• BS, Chemistry

  Bates College

  1980