DAVID BAKER, PH.D.

Dr. Baker received his undergraduate degree from Montana State University, and his graduate degree in behavioral neuroscience from Arizona State University. During Dr. Baker’s postdoctoral training at the Medical University of South Carolina, he worked with Dr. Peter Kalivas to determine the functional importance of nonsynaptic glutamate release mechanisms with the goal of advancing our understanding of the pathological effects of cocaine.  At Marquette, Dr. Baker expanded these studies to determine the therapeutic potential for astrocytic signaling mechanisms to restore cognition impairments present in substance abuse, schizophrenia, and other CNS disorders.

 

Research in the Baker Lab

Despite the remarkable capabilities of our brains, humans display an astonishing capacity for unhealthy, self-destructive behavior.  Poor control over behaviors and thoughts is a critical factor underlying the severity of substance abuse, obesity, schizophrenia, and numerous other CNS disorders. In addition, poor behavioral control exacerbates conditions of cancer, cardiovascular disease, diabetes, and other pathological states that are not immediately recognized as having a CNS component. Therefore, developing cognitive enhancers that better equip people with the ability to suppress unwanted, unhealthy urges and thoughts would be a major breakthrough.    

 

The ideal for any human disease would be to develop medications that exert powerful but highly precise actions in the body that target pathological mechanisms without producing side effects. This has been a critical (and often insurmountable) obstacle for CNS disorders because current neurotherapeutics often act at mechanisms that are critical for neuron-to-neuron signaling involved in numerous types of brain functions. While the rational development of cognitive-enhancing therapeutics has long been a high priority in neuroscience, it has been exceedingly difficult due to the necessity to develop highly selective modulation of signaling underlying cognition without disrupting other forms of brain function. 

 

Paradoxically, cognition may be the most likely of brain functions to rely on molecular mechanisms that are highly specialized and permit the requisite level of precision needed to develop safe, well-tolerated cognitive enhancers.  Enhanced cognitive capabilities of humans and other related species likely required evolved signaling mechanisms that expanded the information processing capacity of the brain.

 

Research in the Baker lab is investigating the therapeutic potential of an evolutionarily new signaling mechanism known as system xc-, which is of particular interest because it releases glutamate, the most powerful excitatory molecule in the brain.  Notably, system xc- is primarily expressed by astrocytes rather than neurons.  These attributes render system xc- as an ideal mechanism to test the idea that therapeutics targeting evolutionarily new signaling mechanisms may exert highly precise changes in the brain to enable enhancement of cognition without producing widespread impairments that lead to poor safety profiles. 

 

This line of research has successfully led to the launching of a biotechnology company, Promentis Pharmaceuticals. Promentis is focused on developing system xc-targeting medications to restore impaired cognition in CNS disorders.  Funding for our academic and commercial endeavors has been provided by private investors as well as grants from the National Institute on Drug Abuse, National Institute of Mental Health, the State of Wisconsin, the Michael J Fox Foundation, and the National Alliance for Research on Schizophrenia and Depression.