MTTResearch


The overarching goal of this MTT is to develop the best practices of translational research and employ these to discover new biomarkers and therapeutic approaches to the addictionsand impulse control disorders. Building on our core strengths in cellular and animal models, clinical science, and chemistry, this MTT is addressing the fundamental gap between the genes, biology and impulsivity which underlies a spectrum of health maladies. Impulsivity or “action without reflection” is an endophenotype for the addictions, aggression/violence and obesity/binge eating disorders, conditions that together account for an incredible portion of the chronic disease burden in the U.S.

We are building on our prior studies that serotonin (5-HT) transmission, particularly through its cognate 5-HT2A receptor (5-HT2AR) and 5-HT2CR proteins, plays a key role in inherent levels of impulsivity, and explore the specific linkage between the biology of the 5-HT2AR/5-HT2CR systems and impulsivity in humans. Our overarching hypothesis is that high tonic/constitutive 5-HT2AR function and low tonic/constitutive 5-HT2CR function are drivers of high impulsivity. To test this hypothesis, we will develop a human subjects laboratory (Specific Aim 1) at UTMB to clinically (Barratt Impulsivity Scale; BIS-11) and experimentally analyze impulsivity in three behavioral tasks (Go/No-Go task, reversal learning task, reward-word Stroop Task). We will recruit healthy human subjects (18-55 yr), collect blood samples and evaluate clinical and behavioral laboratory measures of impulsivity as well as subject history information on addiction, violence and eating behavior.

Current Projects

Determine biomarkers for impulsivity in adolescents (Temple, Van den Berg).

As teen dating violence and disordered weight control behaviors have been linked to impulsive tendencies, two of our MTT projects study both behaviors in adolescents. Both projects collect longitudinal data from adolescents from regional schools. Both Drs. Temple and Van den Berg collect impulsivity data (Barratt Impulsiveness Scale; BIS 11, and modified BIS) from human subjects, and will begin to collect saliva samples to look for biomarkers.

Link epigenetic status of serotonin 2 receptor (5-HT2R) genes to impulsivity and addiction phenotypes (Cunningham, Moeller, Anastasio, Sowers)

Methylation of the 5-HT2AR gene promoter has been implicated as a contributor to schizophrenia and mood disorders, and previous studies revealed that levels of impulsivity positively correlated with 5-HT2AR protein levels. This project looks at the methylation of key residues of 5-HT2AR in cocaine-user human subjects

Develop pipeline to enhance medications development for impulsivity disorders (Cunningham, Gilbertson, Hommel, Zhou)

Current projects include the study and development of small molecule compounds to treat impulsivity disorders including cocaine addiction and relapse and obesity.

Establish best practices in translational research

The goal is to leverage the successes of our various MTT projects to develop new collaborations and projects. MTT members utilize monthly meetings and a web-based collaboration platform to suggest and brainstorm potential collaborations, grant proposals, and paper submissions                 

Investigators

Pharmacology & Toxicology

  • Kathryn Cunningham, Ph.D. *
  • Noelle Anastasio, Ph.D. *
  • Lawrence Sowers, Ph.D. *
  • Jia Zhou, Ph.D. *

Psychiatry

  • Yong-fang Kuo, Ph.D.*
  • Edythe Harvey, Ph.D.
  • Robert Rose, M.D.
  • Christopher Thomas, M.D.*

Preventative Medicine & Community Health

  • Yong-fang Kuo, Ph.D.*
  • Kevin Wooten, Ph.D.

Preventative Medicine & Community Health

  • Jason Glenn, Ph.D.*

Center for Addiction Research

  • Scott Gilbertson, Ph.D. (UH)
  • James Kasper, Ph.D.
  • F. Gerard Moeller, M.D. (VCU)

Obstetrics – Gynecology

  • Jeff Temple, Ph.D.*
  • Donna Le
  • Sara Nowakowski, Ph.D.*
  • Patricia Van den Berg, Ph.D.*

School of Social Work

  • Sunny Shin, Ph.D. (VCU)

*Also members of the Center for Addiction Research
VCU – Virginia Commonwealth University, Richmond, Virginia
UH – University of Houston, Houston, Texas