Stewart Clark PhD

Stewart Clark

Stewart Clark

Associate Professor

Department of Pharmacology and Toxicology

Jacobs School of Medicine & Biomedical Sciences

Specialty/Research Focus

Behavioral Neuroscience; Molecular and Cellular Biology; Neurobiology; Neuropharmacology; Neuroscience

Contact Information
349 Biomedical Research Building
South Campus
Buffalo, New York 14214
Phone: (716) 829-3810

Professional Summary:

The goal of my research is to elucidate the endogenous role of two neuropeptide systems and their potential as therapeutic targets; urotensin II (UII) and neuropeptide S (NPS). Both of these peptides regulate basal ganglia function through G protein-coupled receptor (GPCR) mediated intracellular signals. The basal ganglia are critical in motivated behavior (e.g. food seeking), voluntary movement, and the expression of habits (e.g. compulsions). Basal ganglia dysfunction results in neurological disorders as diverse as Parkinsonism and drug addiction. GPCRs are proven to be amenable to drug development and are targeted by over 30 percent of present day pharmaceuticals. My goal is to exploit the UII and NPS systems to improve the medical treatment of neurological disorders.

Currently my lab is pursuing the following:

1) Determine the role of UIIR activation and the UIIR expressing neurons in reward-related behaviors:. Our results support the need for further investigation of the UII-system as a therapeutic target for treating drug abuse disorders. In addition, we are investigating the i) bias-signaling properties of the endogenous UIIR ligands, and ii) the impact of UIIR single-nucleotide polymorphisms on receptor signaling.

2) We designed a toxin that selectively targets UIIR expressing neurons (cholinergic PPT). In rats the toxin-mediated lesion mimics Progressive Supranuclear Palsy (the most common atypical parkinsonism) on multiple fronts: selective ablation of cholinergic PPT neurons, impaired motor function, and deficits in acoustic startle reaction (MacLaren et al, 2014a; MacLaren et al, 2014b). Our selective cholinergic depletion and a viral-mediated tauopathy rat models are the first to specifically model PSP, and we are further characterizing these models in hope of using them for future drug discovery.

3) During my graduate and post-doctoral training it was found that the central brain administration of neuropeptide S (NPS) in mice enhances memory, is anxiolytic-like (reduced anxiety) and produces hyperlocomotor (increased movement) (Xu et al., 2004; Jungling et al., 2008; Duangdao et al., 2009; Okamura et al., 2011). This is a highly unique behavioral profile. Typically drugs that induce activity and arousal increase anxiety-like behaviors, while drugs that are anxiolytic generally have sedative effects and impair memory. Therefore, the NPS-system could be a therapeutic target for disorders for which fast-acting anxiolytics that augment memory formation would be beneficial (e.g. post-traumatic stress disorder (PTSD)).
In collaboration with the Drug Discovery Center at Research Triangle Institute, we are testing new small molecule NPSR-targeted drug-like compounds.

4) In addition to Drug Discovery for new anxiolytics (#3 above), my lab is also actively testing NPSR ligands for their ability to curb the intake and seeking of drugs of abuse. Current work centers on testing NPSR biased agonists in models of the relapse of drug taking behavior.

Education and Training:

  • PhD, Molecular Neuropharmacology, University of California, Irvine (2003)
  • BS, McMaster University (1997)

Awards and Honors:

  • Distinguished Research Mentor Award (2022)
  • President Emeritus and Mrs. Meyerson Award for Distinguished Undergraduate Teaching and Mentoring (2022)
  • NIDA Travel Award (2010)
  • Post-Doctoral Fellowship (2007)
  • Travel Award (2005)
  • Post-Doctoral Fellowship (2004)

Grants and Sponsored Research:

  • August 2020–August 2024
    Tau accumulation in the pedunculopontine tegmentum as an early node in Progressive Supranuclear Palsy pathogenesis.
    Role: Principal Investigator
  • December 2019–October 2023
    Small molecule biased agonists of the NPS receptor
    Role: Principal Investigator
  • February 2019–February 2022
    Dissecting the Paradox of the Neuropeptide S System
    Role: Principal Investigator

Journal Articles:

See all (19 more)

Professional Memberships:

  • American Society for Pharmaceutical and Experimental Therapeutics (ASPET); Member (2012–present)
  • Member, Society for Neuroscience (1996–present)


  • "The Role of the Cholinergic Pedunculopontine in Parkinsonisms" Rossy Progressive Supranuclear Palsy Center Research Meeting (2021)

Service Activities:

  • Faculty Search Committee; Member (2022–present)
  • Lecturer Search Committee; Member (2022–present)
  • Selection Committee for the 2023 President Emeritus and Mrs. Meyerson Award for Distinguished Undergraduate Teaching and Mentoring; Reviewer (2022)
  • Special Emphasis Panel/Scientific Review Group 2023/01 AGCD-1; Reviewer (2022–present)
  • CSTEP Research Symposium Judge; Judge (2022)
  • Western University, London, ON, Canada. Neuroscience graduate student Faraj Haddad’s PhD defense – Mentor: Susanne Schmid; External Reviewer (2022)
  • Leiboff Award Selection Committee, Behavioral Neuroscience Program - Department of Psychology; Reviewer (2022)
  • LAF-BEB Supervisor Search Committee; Reviewer (2022)
  • ACS Chemical Neuroscience Journal; Reviewer (2021–present)
  • Reviewed Letters of Intent for the CTSI diversity supplements; ad hoc Reviewer (2021–present)
  • Frontiers Cellular Neuroscience Journal; Reviewer (2021–present)
  • PMY 405/406 Curriculum Committee; Member (2021)
  • University Faculty Senate; Member (2020–2022)
  • Frontiers Pharmacology; Reviewer (2020–present)
  • Neurotherapeutics; Reviewer (2020–present)
  • Review the ASPET-SURF Applicants (for CLIMB-UP); ad hoc Reviewer (2020–present)
  • Neuropharmacology Executive Committee of the American Society for Pharmacology and Experimental Therapeutics (ASPET); Member (2016–2020)
  • Admissions Committee; Co-Chair (2011–present)

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Contact Information

349 Biomedical Research Building
South Campus
Buffalo, New York 14214
Phone: (716) 829-3810