Dan Linseman photo

Daniel Linseman

Professor

What I do

I teach courses in Neuropharmacology and Cell Signaling and perform research focused on neurodegenerative disorders and neurotrauma.

Professional Biography

I received my B.S. in Biology and Chemistry from the University of Michigan in 1987. I then worked for 8 years as a research technician at the Upjohn Company in Kalamazoo, Michigan. I went back to the University of Michigan in 1996 and completed my PhD there in Pharmacology in 2000. I did my postdoctoral training from 2000-2005 at the Denver VA Medical Center and received my first independent VA grant in 2006. I held a joint appointment with the VA and DU from 2006-2015 and have been full time on the faculty at DU since 2015.

Degree(s)

  • Ph.D., Pharmacology, University of Michigan, 2000

Research

Research in the Linseman Lab at DU is focused on elucidating molecular mechanisms of neuronal cell death in degenerative disorders and episodes of neurotrauma, with a particular emphasis on amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), Alzheimer’s disease (AD), traumatic brain injury (TBI), and most recently, neurological long COVID. I am a Professor in the Department of Biological Sciences and a Senior Scientist in the Knoebel Institute for Healthy Aging at the University of Denver. I have previously been funded by the NIH (R01NS062766; R01AG071228 – current award) and the VA (10 years of Merit Review funding) and have more than 80 peer-reviewed publications. According to Google Scholar, my published works have been cited more than 6000 times and I have an author H-index of 40.

In my laboratory, biochemical, immunofluorescence, and molecular biological techniques are used to examine the roles of mitochondrial oxidative stress, neuroinflammation, and intrinsic apoptosis in neurodegeneration and neurotrauma. We utilize mouse models of neurodegenerative disorders (e.g., mutant hSOD1 transgenic mouse model of ALS and 3xTg-AD mouse model of AD) and TBI (e.g., controlled cortical impact mouse model of TBI) to study disease processes in vivo. We also collaborate extensively with neurosurgeons and neurologists to assess clinical data and biomarkers, including exosomal cargo, from patients with a history of TBI and neurological long COVID, as well as ALS and AD.

Specific ongoing projects include the following: elucidating the relationship between TBI, COVID-19 and neurodegeneration, analyzing exosomal biomarkers of neuronal injury and inflammation in patients and TBI mouse models (current R01), investigating the role of Reelin deficiencies in the pathogenesis of AD, the role of Rho family GTPases in the motor neuron cell death that underlies ALS, the role of mitochondrial glutathione transport in protecting neurons from oxidative stress, involvement of Bcl-2 family proteins in the regulation of mitochondrial susceptibility to oxidative stress, and studies on the antioxidant, anti-neuroinflammatory, and neuroprotective properties of a variety of natural products.

Key Projects

  • Exosome biology in Alzheimer's disease and concussion.
  • Phase 2a Open-Label Preliminary Biomarker Study of WP-0512 in Patients with ALS
  • Synthetic Protein Mimetics based Specific Targeting and Degradation of TDP-43 Aggregation Associated with ALS
  • Regulation of Mitochondrial Oxidative Stress by Bcl-2 family Proteins

Featured Publications

Stankiewicz, T. (2020). Dysregulation of Rac or Rho elicits death of motor neurons and activation of these GTPases is altered in the G93A mutant hSOD1 mouse model of amyotrophic lateral sclerosis. (C. Pena, R. Bouchard, & D. A. Linseman, Eds.). Neurobiol Dis.
Winter, A., & Linseman, D. A. (2017). A cystine-rich whey supplement (Immunocal®) provides neuroprotection from diverse oxidative stress-inducing agents in vitro by preserving cellular glutathione. Oxid Med Cell Longev.
Winter, A., Ross, E., Wilkins, H., Stankiewicz, T., Wallace, T., Miller, K. E., & Linseman, D. A. (2017). An anthocyanin-enriched extract from strawberries delays disease onset and extends survival in the hSOD1G93A mouse model of amyotrophic lateral sclerosis. Nutritional Neuroscience, 1-13.

Presentations

Linseman, D. (2017). Current Progress on Nutraceutical Therapies for ALS. ALS Association Rocky Mountain Chapter, Ask the Experts Symposium: 1965.
Linseman, D. (2017). Effects of Immunocal® in vitro and in mouse models of ALS and TBI. Immunotec, Inc, Quebec, CA: 1965.
Linseman, D. A. (2015). Let food be thy medicine. DU college enrichment program.
Linseman, D. A. (2015). Nutritional avenues to brain health. DU all campus lecture.
Linseman, D. (2017). Novel Nutraceutical Therapies for ALS. University Hills Rotary Club: 1965.

Awards

  • "Excellence in Care" Award, ALS Association, Rocky Mountain Chapter