Brian HermanProfessor, Department of Biomedical Engineering
Minneapolis, MN 55455
Research & Teaching
Publications & Awards
Our research is focused on the role and regulation of caspase-2 (Casp2) in degenerative diseases that accompany aging.
Our laboratory was the first to describe a role for Casp2 in aging, and subsequent work from our group has documented that Casp2 regulates cellular redox status and is necessary for mitochondrial ROS-induced apoptosis in neurons.
In neuronal cells and tissue, our laboratory was the first to demonstrate that Casp2 resides in brain mitochondrial matrix; is activated in a mitochondrial ROS-dependent fashion; mediates apoptosis directly from the mitochondrial compartment; and loss of Casp2 increases resistance of the nigrostriatal dopaminergic pathway to MPTP-induced toxicity. Interestingly, the normal function of mature CNS neurons does not appear to require Casp2. In contrast, Casp2 mediates damage to CNS neurons under stress (e.g., excitotoxicity, increased ROS, exposure to Aβ or MPTP, neonatal stroke, retinal ischemia and transgenic expression of mutant APP, huntingtin or tau), suggesting that targeting Casp2 may benefit multiple neurological conditions.
We also were the first to describe a novel role for Casp2 as a negative regulator of autophagy via downregulation of the MTOR pathway and upregulation of AMPK activation. Most recently, our research has focused on the role of Casp2 in tauopathies.
Because of his research contributions he has been awarded multiple honors including being listed in American Men and Women of Science, American Cancer Society Faculty Research Award, Presidential Distinguished Senior Scholar Award, Who’s Who in American Education, Dozer Fellowship from Ben Gurion University, Israel and two 10 year Method to Extend Research in Time (MERIT) Award, awarded by the National Institutes of Health to the top 1-2% scientists in the US.
Lopez-Cruzan M, Sharma R, Tiwari M, Karbach S, Holstein D, Martin CR, Lechleiter JD, Herman B. Caspase-2 resides in the mitochondria and mediates apoptosis directly from the mitochondrial compartment. Cell Death Discov. 2016 Feb 15;2. pii: 16005.
Callaway, D., Riquelme, M., Sharma, R., Lopez-Cruzan, M.,Herman, B., and Jiang, J. Caspase-2 Regulates Osteoclastogenesis through Downregulation of Oxidative Stress Bone. 2015 Jul;76:40-8. doi: 10.1016/j.bone.2015.03.006. Epub 2015 Mar 19. Erratum in: Bone. 2016 Dec;93:233-234.
Tiwari M., Sharma L.K., Vanegas D., Callaway D.A., Bai Y., Lechleiter J.D., Herman B. A nonapoptotic role for CASP2/caspase 2: Modulation of autophagy. Autophagy 2014; 10:1054 - 1070; http://dx.doi.org/10.4161/auto.28528
Sharma R, Callaway D, Vanegas D, Bendele M, Lopez-Cruzan M, Horn D, Guda T, Fajardo R, Abboud- Werner S, Herman, B. Caspase-2 maintains bone homeostasis by inducing apoptosis of oxidativelydamaged osteoclasts. PLoS One. 2014 Apr 1;9(4):e93696. doi: 10.1371/journal.pone.0093696. eCollection 2014.
Lopez-Cruzan, M. and Herman, B., Loss of caspase-2 accelerates age-dependent alterations in mitochondrial production of reactive oxygen species. Biogerontology Volume 14, Issue 2, April 2013, Pages 121-130
Klionsky, D. J., Herman, B. et. al., Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8:4, 1-100; April 2012
Tiwari M, Herman, B, and Morgan W. A knockout of the caspase 2 gene produces increased resistance of the nigrostriatal dopaminergic pathway to MPTP-induced toxicity.(2011) Exp Neurol. Jun;229(2):421-8.
Tiwari, M., Lopez-Cruzan, M., Morgan, W.W., and Herman, B. Loss of caspase-2 dependent apoptosis induces autophagy following mitochondria oxidative stress in primary cultures of young- adult cortical neurons. J. Biol. Chem. published January 7, 2011 as doi:10.1074/jbc.M110.163824