Mark Petersen, MD
Associate Professor
Pediatrics
School of Medicine

My work seeks to identify new therapies for neurological diseases by targeting toxic blood proteins and inflammatory signals at the blood-brain interface that block normal brain development and repair. To achieve this goal, our group has developed a multifaceted research program incorporating basic science studies of stem cells and animal models with translational studies of human tissue and blood biomarkers. We have discovered critical links between blood coagulation, inflammation, and stem cell dysfunction in neurological disease. The nervous system has long been defined by its limited capacity for regeneration which results in persistent neurological deficits after nervous system damage. Stem cells are abundant in the brain, but why these stem cells are unable to fully restore neural tissue after injury has remained a mystery. We found that the blood clotting protein fibrinogen causes inflammation in the brain and blocks stem cells from becoming mature, myelin-repairing cells. We are now designing therapies to overcome the inhibitory environment in the damaged nervous system to promote regeneration and normal brain development.

Through collaborations with the UCSF Preterm Birth Initiative and UCSF Newborn Brain Research Institute, we are also extending our studies to explore how maternal inflammation and coagulation contribute to preterm birth and poor neonatal outcomes. By combining large population datasets with state-of-the-art multiplex and proteomic approaches to measure blood biomarkers, we hope to identify druggable pathways at the maternal-fetal interface that can be targeted to prevent or lessen the impact of preterm birth and neonatal brain injury.

• Newborn metabolic vulnerability profile identifies preterm infants at risk for mortality and morbidity.
  Pediatric research 2020 Oltman SP, Rogers EE, Baer RJ, Jasper EA, Anderson JG, Steurer MA, Pantell MS, Petersen MA, Partridge JC, Karasek D, Ross KM, Feuer SK, Franck LS, Rand L, Dagle JM, Ryckman KK, Jelliffe-Pawlowski LL
• Author Correction: Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation.
  Nature immunology 2020 Mendiola AS, Ryu JK, Bardehle S, Meyer-Franke A, Ang KK, Wilson C, Baeten KM, Hanspers K, Merlini M, Thomas S, Petersen MA, Williams A, Thomas R, Rafalski VA, Meza-Acevedo R, Tognatta R, Yan Z, Pfaff …
• Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation.
  Nature immunology 2020 Mendiola AS, Ryu JK, Bardehle S, Meyer-Franke A, Ang KK, Wilson C, Baeten KM, Hanspers K, Merlini M, Thomas S, Petersen MA, Williams A, Thomas R, Rafalski VA, Meza-Acevedo R, Tognatta R, Yan Z, Pfaff …
• Neurovascular interactions: Mechanisms, imaging, and therapeutics.
  IBRO Reports 2019 Katerina Akassoglou, Reshmi Tognatta, Mark Petersen
• Fibrin-targeting immunotherapy protects against neuroinflammation and neurodegeneration.
  Nature immunology 2018 Ryu JK, Rafalski VA, Meyer-Franke A, Adams RA, Poda SB, Rios Coronado PE, Pedersen LØ, Menon V, Baeten KM, Sikorski SL, Bedard C, Hanspers K, Bardehle S, Mendiola AS, Davalos D, Machado MR, Chan JP, …
• Spatiotemporal distribution of fibrinogen in marmoset and human inflammatory demyelination.
  Brain : a journal of neurology 2018 Lee NJ, Ha SK, Sati P, Absinta M, Luciano NJ, Lefeuvre JA, Schindler MK, Leibovitch EC, Ryu JK, Petersen MA, Silva AC, Jacobson S, Akassoglou K, Reich DS
• Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics.
  Nature reviews. Neuroscience 2018 Petersen MA, Ryu JK, Akassoglou K
• Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage.
  Neuron 2017 Petersen MA, Ryu JK, Chang KJ, Etxeberria A, Bardehle S, Mendiola AS, Kamau-Devers W, Fancy SPJ, Thor A, Bushong EA, Baeza-Raja B, Syme CA, Wu MD, Rios Coronado PE, Meyer-Franke A, Yahn S, Pous L, Lee…
• Blood coagulation protein fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation.
  Nature communications 2015 Ryu JK, Petersen MA, Murray SG, Baeten KM, Meyer-Franke A, Chan JP, Vagena E, Bedard C, Machado MR, Rios Coronado PE, Prod'homme T, Charo IF, Lassmann H, Degen JL, Zamvil SS, Akassoglou K
• Early detection of thrombin activity in neuroinflammatory disease.
  Annals of neurology 2014 Davalos D, Baeten KM, Whitney MA, Mullins ES, Friedman B, Olson ES, Ryu JK, Smirnoff DS, Petersen MA, Bedard C, Degen JL, Tsien RY, Akassoglou K
• 220 Fibrinogen/CR3 signaling induces demyelination by promoting Th1 cell differentiation and peripheral macrophage recruitment into the CNS.
  Cytokine 2013 Jae Kyu Ryu, Kim M. Baeten, Mark A. Petersen, Sara G. Murray, Anke Meyer-Franke, Dimitrios Davalos, Catherine Bedard, Thomas Prod’homme, Israel F. Charo, Hans Lassmann, Jay L. Degen, Scott S. Zamvil, …
• Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation.
  Nature communications 2012 Davalos D, Ryu JK, Merlini M, Baeten KM, Le Moan N, Petersen MA, Deerinck TJ, Smirnoff DS, Bedard C, Hakozaki H, Gonias Murray S, Ling JB, Lassmann H, Degen JL, Ellisman MH, Akassoglou K
• Diverse microglial motility behaviors during clearance of dead cells in hippocampal slices.
  Glia 2004 Petersen MA, Dailey ME