Jeremy Marks, M.D.


  • Associate Professor, Department of Pediatrics, Committee on Molecular Medicine/MPMM, Committee on Cell Physiology & Neurobiology, Committee on Molecular Metabolism & Nutrition


Ph.D., University of California, Los Angeles
M.D., McMaster University


The University of Chicago
KCBD 4130
900 East 57th Street
Chicago, Illinois 60637

Phone: (773) 795-7650

Website (Comer Children's Hospital)


Developmental regulation of neuronal vulnerability to injury; polymer-mediated cell repair

A major focus of the laboratory is understanding the cellular and molecular mechanisms by which neuronal vulnerability to injury increases during postnatal maturation. We have developed techniques to maintain hippocampal neurons from postnatal animals in tissue culture. Using these cells, we investigate the intracellular mechanisms that underlie developmentally regulated neuronal responses to injury. Using time-lapse, multi-mode imaging of single neurons, we have found that vulnerability of cultured postnatal hippocampal neurons increases with postnatal age, and that this vulnerability increase depends on progressive loss of intracellular calcium ([Ca2+]i) homeostasis. Because mitochondria play important roles in [Ca2+]i homeostasis, we have focused on mitochondrial calcium ([Ca2+]mito) and membrane potential (Dy ) responses to excitotoxicity. We have found marked differences in excitotoxicity-induced Dy dissipation and Ca2+ accumulation as a function of postnatal age. These observations are consistent with the hypothesis that mitochondria are important determinants of the increased vulnerability to injury that accompanies maturation. Our observations that these differences depend on nitric oxide (NO) production have prompted our current studies of developmental differences in the magnitude of Ca2+-dependent NO synthesis, production of superoxide, and potential differences in cofactors for NO synthase. The central nature of mitochondrial function to the determination of neuronal vulnerability to injury has prompted us to begin determining developmental differences in mitochondrial mechanism of Ca2+ uptake and extrusion.

A second focus of the laboratory is a class of compounds, the amphiphilic tri-block copolymers. We have determined that these compounds, of which Poloxamer 188 (P188, BASF, Germany) is the prototype, provide profound neuroprotection in vitro following stimuli resulting in necrosis, such as excitotoxicity, and reactive oxygen species, but not those primarily inducing apoptosis. Because P188 inserts into the plasma membrane, and can restore membrane integrity following electroporation, our hypothesis is that these interactions with the plasma membrane mediate neuroprotection. Current projects include determining neuroprotective efficacy following such important clinical conditions as anoxia and metabolic inhibition in vitro, and hypoxia-ischemia in an animal model in vivo.

Research Papers in PubMed