Daniel Linseman

Assistant Professor, Department of Biological Sciences

Research Interests:

Unraveling the Role of Cell Death in Neurodegeneration

The principal research focus of Dr. Linseman’s laboratory is to elucidate the molecular mechanisms by which neurons die in various neurodegenerative disorders. A major emphasis is to understand the role of mitochondrial oxidative stress and intrinsic apoptosis (programmed cell death) in neurodegeneration. Specific projects that are currently ongoing in the laboratory include: 1) identification of novel pathways by which pro-survival Bcl-2 proteins (eg., Bcl-2 and Mcl-1) protect neurons from mitochondrial oxidative stress and apoptosis, 2) determination of the mechanisms by which pro-death Bcl-2 proteins (eg., Bim and Puma) trigger mitochondrial oxidative stress and apoptosis, and 3) evaluation of natural product polyphenolic antioxidants (eg., green tea EGCG and red grape resveratrol) for their neuroprotective effects against mitochondrial oxidative stress and neuronal apoptosis. The laboratory routinely utilizes primary cultures of neurons obtained from rat cerebellum as an in vitro model to investigate neuronal apoptosis. The laboratory also employs mouse models of Parkinson’s disease and amyotrophic lateral sclerosis to study neuronal apoptosis in vivo. Ultimately, Dr. Linseman hopes to identify novel regulators of mitochondrial oxidative stress and intrinsic apoptosis that can be targeted to limit neuronal loss and slow the progression of various neurodegenerative diseases.

• Loucks FA, Schroeder EK, Zommer AE, Hilger S, Kelsey NA, Bouchard RJ, Blackstone C, Brewster JL, and Linseman DA (2009) Caspases indirectly regulate cleavage of the mitochondrial fusion GTPase OPA1 in neurons undergoing apoptosis. Brain Res. 1250, 63-74. (DOI: 10.1016/j.brainres.2008.10.081)
• Schroeder EK, Kelsey NA, Doyle J, Breed E, Bouchard RJ, Loucks FA, Harbison RA, and Linseman DA (2009) Green tea epigallocatechin 3-gallate accumulates in mitochondria and displays a selective anti-apoptotic effect against inducers of mitochondrial oxidative stress in neurons. Antiox. & Redox Sig. 11, 469-480.
• Linseman DA (2009) Targeting oxidative stress for neuroprotection. Antiox. & Redox Sig. 11, 421-424. (DOI: 10.1089/ARS.2008.2236)
• Linseman DA and Loucks FA (2008) Diverse roles of Rho family GTPases in neuronal development, survival, and death. Front. Biosci. 13, 657-676. (DOI: 10.2741/2710)
• Zimmermann AK, Loucks FA, Schroeder EK, Bouchard RJ, Tyler KL, and Linseman DA (2007) Glutathione binding to the Bcl-2 homology-3 domain groove: a molecular basis for Bcl-2 antioxidant function at mitochondria. J. Biol. Chem. 282, 29296-29304. (DOI: 10.1074/jbc.M702853200)
• Loucks FA, Le SS, Zimmermann AK, Ryan KR, Barth H, Aktories K, and Linseman DA (2006) Rho family GTPase inhibition reveals opposing effects of MEK/ERK and JAK/STAT signaling cascades on neuronal survival. J. Neurochem. 97, 957-967. (DOI: 10.1111/j.1471-4159.2006.03802.x)