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Faculty Highlight: Chris Gregg

Sep 01, 2019

Christopher Gregg is Associate Professor of Neurobiology & Anatomy and Human Genetics. His lab is developing new technologies and approaches to discover how the genome creates complex behavioral traits and is elucidating new mechanisms and concepts that contribute to brain disorders and diseases.

Exciting new developments in the Gregg lab:

  • Dr. Christopher Gregg was awarded tenure this summer and has been promoted to Associate Professor.
  • The Gregg lab received 2 new NIH grants! One grant will explore how gene regulatory mechanisms discovered from hibernating mammals can inform strategies to prevent Alzheimer’s Disease and age-related obesity. The other grant will develop novel allele-specific transgenic reporter technologies to study gene regulation at the allele and cellular level in vivo in the brain.
  • An exciting new collaboration between the Gregg lab and the Gertz lab (Huntsman Cancer Institute) will develop a new CRISPR-Cas9 technology called Enhancer-interference for in vivo epigenome editing. This technology could revolutionize our ability to learn how the epigenome regulates disease phenotypes, including those involved in Alzheimer’s Disease and mental illness. This project is supported by the Utah Genome Project.
  • Dr. Paul Bonthuis, a postdoc in the Gregg lab, has received a prestigious K99 award and was recently hired as a new tenure-track faculty member at the University of Illinois!
  • Dr. Wei-Chao Huang, a graduate student from the Gregg lab, got a new outstanding postdoc position in which he will be co-mentored by labs at Amgen and the Harvard Medical School!
  • Dr. Gregg’s new machine learning approach for making sense of complex behavior patterns was just published in the high impact journal Cell Reports – and got the cover of the journal!
  • The Gregg lab’s comparative genomics research program that is mining animal genomes to solve human health problems was selected by STAT news this year as one of the top medical research breakthroughs in 2018. Congrats to Elliott Ferris – the scientist leading this work!
  • Stephanie Kravitz, a graduate student co-mentored by Dr. Gregg and Dr. Aaron Quinlan (Human Genetics Department), won a Center for Clinical & Translational Sciences fellowship and was selected to enter the week long Leena Peltonen School of Human Genomics program being held at the Eurotel Victoria – Les Diablerets, Switzerland!
  • The Gregg lab’s innovations are being highlighted in this year’s Annual Report from the University of Utah’s Technology Commercialization & Venture office.
Dr. Gregg believes that the secrets to shaping different brain functions and behavioral patterns are hidden in the 98% of the genome that does not contain protein-coding genes, but instead functions to control when and where genes are turned on and off. Recently, his lab made discoveries that challenge the assumption that the maternal and paternal copies of genes (alleles) are regulated equally. His lab has found evidence that some subpopulations of brain cells prefer to express either the maternally or paternally inherited alleles of some genes, including important genes involved in dopamine synthesis. The Gregg lab further discovered genes and brain cells that randomly choose to express either the maternal or paternal alleles, rather than expressing both alleles equally. These findings have helped open a new area of inquiry focused on understanding gene regulation at the allele and cellular level.
Gene expression is controlled by discrete regulatory elements in the genome that act like switches controlling gene activity in a developmental stage, context and cell-type dependent manner. Most of the important regulatory elements in the genome are undiscovered and uncharacterized. Generally, we do not know the identity of the critical regulatory elements controlling most clinically important phenotypes. To address this problem, the Gregg lab recently used comparative genomics methods to identify deeply conserved noncoding elements in the mammalian genome and then link each individual element to specific clinical phenotypes. The secret sauce to finding candidate elements for different phenotypes turned out to involve analyzing evolutionary changes to the genomes of species that evolved biomedical superpowers. Candidate regulatory elements for controlling cancer resistance and somatic mutation rates were uncovered from the elephant genome. Elements for controlling mammalian obesity, diabetes and neurodegeneration were uncovered from hibernating mammals. Overall, the Gregg lab has analyzed the genomes of nearly 20 different species with biomedical superpowers and created an atlas of candidate functional elements for specific clinical phenotypes. In a new collaboration with Dr. Jay Gertz, the Gregg lab is now embarking on the development of new epigenome editing technologies to repress and activate combinations of elements to engineer disease prevention superpowers in mammals.
Linking underlying genetic and epigenetic mechanisms to specific aspects of brain function and behavior has been very challenging in the neurosciences. Most studies focus on highly simplified and controlled behavioral responses. Consequently, the principles and mechanisms involved in constructing complex behavior patterns are not well defined. Complex ethological behaviors could be constructed from finite modules that are reproducible functional units of behavior. Recently, the Gregg lab tested this idea and developed machine-learning methods to dissect rich behavior patterns in mice. They uncovered discrete modules of behavior, which are reproducible behavioral sequences across many individuals. Modules range from hundreds of seconds to less than 1 second in duration. Modules differ in terms of form, expression frequency, and expression timing and are expressed in a probabilistically determined order. Overall, the Gregg lab found that complex behavior patterns are built from finite, genetically controlled modules. The Gregg lab’s new approach helps open up a new conceptual framework and methods for understanding the mechanistic basis of different behavior patterns. The lab is currently building on these findings to create a major new initiative focused on “precision behavioral medicine”, which will enhance our ability to evaluate clinically important behavior patterns and relate specific aspects of behavior to underlying biological mechanisms.