Dr. Chris Gregg PhD

Written By Jeff Barson
 

Co-founder & Chief Science Officer, Storyline Health
Professor of Neurobiology & Anatomy and Human Genetics
University of Utah School of Medicine

I completed my PhD in Canada with Gairdner Award winner, Dr. Samuel Weiss (University of Calgary), who discovered adult neural stem cells in the brain. In 2004, I participated in the founding of a biotechnology company called Stem Cell Therapeutics, which developed treatments for Stroke & Multiple Sclerosis. Following this, I was awarded a Human Frontiers Fellowship and moved to Harvard University to train as a postdoctoral fellow with Dr. Catherine Dulac (Howard Hughes Medical Institute) and was among the first to develop RNASeq for allele-specific expression analysis. I was awarded the 2010 Eppendorf & Science Prize and became a New York Stem Cell Foundation Robertson-Neuroscience Investigator. Currently, I am a tenured professor at the University of Utah in Departments of Neurobiology & Human Genetics. My research is focused on understanding how gene regulatory mechanisms shape brain functions and complex behavior patterns in health and disease. I love ideas, discovery and working with and mentoring creative people!

 
University of Utah Health

ASSOCIATE PROFESSOR OF NEUROBIOLOGY & ANATOMY AND HUMAN GENETICS, UNIVERSITY OF UTAH SCHOOL OF MEDICINE

Scientists in my laboratory are developing novel technologies to understand genetic and epigenetic mechanisms in the brain that influence brain function and disease. We have developed novel approaches that allow us to study differences in the behavior and function of the gene copies we inherit from our mother compared to our father. The lab is highly interdisciplinary. Computer scientists focus on the development of new software and data analysis and visualization technologies to analyze genome-scale data and high-throughput behavior data. Bench scientists in the lab are developing novel behavioral screens, as well as molecular biology, genome engineering and imaging approaches to study brain function and behavior. We have particular interests in feeding and motivated behaviors, and in autism, addiction and eating disorder research.

Gregg Lab - University of Utah School of Medicine >

 
Harvard University - Catherine Dulac Labratory

POSTDOCTORAL FELLOW - CATHERINE DULAC LABORATORY
HARVARD UNIVERSITY

As a postdoctoral fellow with Dr. Catherine Dulac in the Department of Cellular and Molecular Biology at Harvard University, my research focused on the development of novel genomics approaches based on high throughput sequencing technology to understand how genes influence sexually dimorphic brain functions and behaviors.

 
Univesity of Calgary - Sam Weis Lab

PHD - NEUROSCIENCE
UNIVERSITY OF CALGARY

PhD was performed in neural stem cell biology under the supervision of Dr. Samuel Weiss. Dr. Weiss is best known for his discovery of adult neural stem cells in 1992 and the development of the neurosphere culture system.

 
 

Academic Research Overview

A major goal of our research is to uncover novel genetic and epigenetic mechanisms in the brain that regulate motivated behaviors. Alterations to motivated behaviors occur in a wide range of disorders, including anxiety disorders, major depression, addiction, bipolar disorder, autism spectrum disorders and eating disorders. Motivated beahviors involve opposing behavioral drives, such as hunger and satiety, reward and aversion, sleep and wake, or social and anti-scoial behaviors. The Gregg Lab is developing novel approaches to study complex motivated behaviors and to uncover functionally antagonistic pathways that regulate opposing motivational states. Our goal is to develop approaches to engineer specific patterns of behavior and to develop novel strategies to diagnose and treat complex psychiatric disorders. We are developing novel computation, genomics genome engineering and behavioral approaches to achieve these goals.

Academic Areas of interest

Allele-Specific Expression Effects in Neuronal Circuits Regulating Motivated Behaviors. We are developing novel genomics and imaging based approaches to study allele-specific expression effects in different neuronal circuits that regulate anxiety, feeding exploration and other complex motivated behaviors. In particular, we have been focused on a form of allele-specific expression called genomic imprinting, in which the maternally or paternally inherited allele is preferentially expressed for some genes in the genome. We have discovered numerous imprinting effects that influence gene expression in specific tissues and regions of the brain. Our goal is to understand the function and regulation of the seffects and how they influence brain function and susceptibility to brain disorders.

Deconstruction of Complex Motivated Behaviors. Our lab has extensive expertise in the analysis of large-scale datasets. We are building on our expertise to develop novel approaches to study complex patterns of behavior. Using machine learning and video tracking, we are designing "high-content behavioral assays" that allow us to deconstruct motivated behaviors, such as foraging behavior, into over 200 distinct behavioral measures. We are developing these methods to study mechanisms that regulate the development of complex motivated behaviors in offspring and to perform unbiased screens for behavioral phenotypes in transgenic mice and mouse models of brain disorders.

Defining Functionally Antagonistic Mechanisms that Regulate Behavioral Drives. Using computational and genomics approaches, we are developing enw methods to "decode" gene networks in the brain to find functionally antagonistic pathways that regulate behavioral drives. Following the discovery of candidate opposing mechanisms, we use genome engineering based approaches, such as CRISPR technology and viral gene delivery, in combination with mouse genetics and novel behavioral screens to test for functionally antagonistic effects on specific aspects of behaviour. We expect that defining these mechanisms in the brain will transform our ability to diagnose and treat a wide range of psychiatric disorders and human health issues.

 
 

The Gregg Lab

The Gregg lab is a neurogenetics lab working to uncover new knowledge and technologies to improve brain function and reduce the risk for developing mental illnesses and other disorders. Our highly interdisciplinary research program merges genomics, epigenetics, evolutionary biology and big data analysis methods with neuroscience and behavior analysis. Trainees develop expertise in genomics, bioinformatics, phylogenomics, genome engineering, molecular biology, programming, statistical modeling, imaging, disease biology, biotechnology, neurobiology and behavior analysis.

The Gregg Lab has three unique areas of focus:

  1. Do epigenetic mechanisms differentially shape the expression of the maternal and paternal gene copies (alleles) that offspring inherit from their parents? This work is contributing to a new picture of how genes and the environment interact to shape offspring phenotypes and disease risks and inspiring new approaches to disease prognostics.

  2. We are using new phylogenomics approaches to uncover putative master functional regulatory elements in the mammalian genome that shape social behaviors, cancer risk, motivated behaviors and metabolic phenotypes.

  3. We have developed 3D printing, computer vision and machine learning technologies to perform high throughput behavioral screening in mice. We are using this approach to learn how specific regulatory elements and epigenetic mechanisms impact offspring behavioral development and brain function.

References

  1. Ferris E, Abegglen LM, Schiffman JD, Gregg C (2018). Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance. Cell Reports 22(10):2742-2755

  2. Huang WC, Ferris E, Cheng T, Hörndli CS, Gleason K, Tamminga C, Wagner JD, Boucher KM, Christian JL, Gregg C (2017). Diverse Non-genetic, Allele-Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain. Neuron 93(5):1094-1109.e7.

  3. Bonthuis PJ, Huang WC, Stacher Hörndli CN, Ferris E, Cheng T, Gregg C (2015) Noncanonical Genomic Imprinting Effects in Offspring. Cell Reports 12(6):979-91

  4. Gregg C (2014) Known unknowns for allele-specific expression and genomic imprinting effects. Review. F1000Prime Reports 6:75. doi: 10.12703/P6-75

  5. Gregg C (2010) Parental control over the brain. Science 330(6005):770-1 (Eppendorf winner)

  6. Gregg C, Zhang J, Butler JE, Haig D, Dulac C (2010) Sex-specific parent-of-origin allelic expression in the mouse brain. Science 329(5992):682-5

  7. Gregg C, Zhang J, Weissbourd B, Luo S, Schroth GP, Haig D, Dulac C (2010) High-resolution analysis of parent-of-origin allelic expression in the mouse brain. Science 329(5992):643-8

Selected Publications

Journal Article

  1. Elliott Ferris, Lisa M Abegglen, Joshua D Schiffman, Christopher Gregg (2018). Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance. Cell Rep, 22(10), 2742-2755.

  2. Huang WC, Ferris E, Cheng T, Hrndli CS, Gleason K, Tamminga C, Wagner JD, Boucher KM, Christian JL, Gregg C (2017). Diverse Non-genetic, Allele-Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain. Neuron, 93(5), 1094-1109.

  3. Bonthuis P, Huang WC, Statcher Horndli C, Ferris E, Cheng T, Gregg C (2015). Noncanonical genomic imprinting effects in offspring. Cell Rep, 12(6), 979-91.

  4. McKenna S, Meyer M, Gregg C, Gerber S (2015). s-CorrPlot: An Interactive Scatterplot for Exploring Correlation. J Comput Graph Stat, 25(2,2016).

  5. Gregg C, Zhang J, Butler JE, Haig D, Dulac C (2010). Sex-specific parent-of-origin allelic expression in the mouse brain. Science, 329(5992), 682-5.

  6. Gregg C, Zhang J, Weissbourd B, Luo S, Schroth GP, Haig D, Dulac C (2010). High-resolution analysis of parent-of-origin allelic expression in the mouse brain. Science, 329(5992), 643-8.

  7. Gregg C (2009). Pregnancy, Prolactin and White Matter Regeneration. Journal of Neurological Sciences, 285(1-2), 22-7.

  8. Mak GK, Enwere EK, Gregg C, Pakarainen T, Poutanen M, Huhtaniemi I, Weiss S (2007). Male pheromone-stimulated neurogenesis in the adult female brain: possible role in mating behavior. Nat Neurosci, 10(8), 1003-11.

  9. Gregg C, Shikar V, Larsen P, Mak G, Chojnacki A, Yong VW, Weiss S (2007). White matter plasticity and enhanced remyelination in the maternal CNS. J Neurosci, 27(8), 1812-23.

  10. Ohta S, Gregg C, Weiss S (2006). Pituitary adenylate cyclase-activating polypeptide regulates forebrain neural stem cells and neurogenesis in vitro and in vivo. J Neurosci Res, 84(6), 1177-86.

  11. Kolb B, Morshead C, Gonzalez C, Kim M, Gregg C, Shingo T, Weiss S (2006). Growth factor-stimulated generation of new cortical tissue and functional recovery after stroke damage to the motor cortex of rats. J Cereb Blood Flow Metab, 27(5), 983-97.

  12. Gregg C, Weiss S (2005). CNTF/LIF/gp130 receptor complex signaling maintains a VZ precursor differentiation gradient in the developing ventral forebrain. Development, 132(3), 565-78.

  13. Enwere E, Shingo T, Gregg C, Fujikawa H, Ohta S, Weiss S (2004). Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci, 24(38), 8354-65.

  14. Gregg C, Weiss S (2003). Generation of functional radial glial cells by embryonic and adult forebrain neural stem cells. J Neurosci, 23(37), 11587-601.

  15. Chojnacki A, Shimazaki T, Gregg C, Weinmaster G, Weiss S (2003). Glycoprotein 130 signaling regulates Notch1 expression and activation in the self-renewal of mammalian forebrain neural stem cells. J Neurosci, 23(5), 1730-41.

  16. Shingo T, Gregg C, Enwere E, Fujikawa H, Hassam R, Geary C, Cross JC, Weiss S (2003). Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin. Science, 299(5603), 117-20.

Review

  1. Gregg C (2017). The emerging landscape of in vitro and in vivo epigenetic allelic effects. [Review]. F1000Res, 6(2108).

  2. Gregg C (2014). Known unknowns for allele-specific expression and genomic imprinting effects. [Review]. F1000Res, 4(6), 75-77.

  3. Gregg C (2010). Eppendorf winner. Parental Control Over The Brain. [Review]. Science, 330(6005), 770-1.

  4. Gregg C (2009). Pregnancy, Prolactin and White Matter Regeneration. [Review]. Journal of Neurological Sciences, 285(1-2), 22-7.

  5. Gregg CT, Chojnacki AK, Weiss S (2002). Radial glial cells as neuronal precursors: the next generation? [Review]. J Neurosci Res, 69(6), 708-13.

  6. Gregg CT, Shingo T, Weiss S (2001). Neural stem cells of the mammalian forebrain. [Review]. Symp Soc Exp Biol, (53), 1-19.

Book Chapter

  1. Bonthuis P and Gregg C (2015). Decoding the Transcriptome of Neuronal Circuits. In Adam Douglass (Ed.), New Techniques in Systems Neuroscience (pp. 29-56). New York: Springer.

  2. Huang, WC and Gregg C (2013). Genomic Imprinting in the Mammalian Brain. In R Kageyama, T. Yamamori (Eds.), Cortical development: neural diversity and neocortical organization. Springer.

  3. Dulac, C and Gregg C (2013). Genomic imprinting in the Adult and Developing Brain. In: Multiple Origins of Sex Differences in Brain. In D.W. Pfaff and Y. Christen (Eds.), Research and Perspectives in Endocrine Interactions. Springer-Verlag Berlin Heidelberg.

  4. Gregg C, Shingo T, and Weiss S (2001). Neural Stem Cells of the Forebrain. In J.A. Miyan et al. (Ed.), Brain Stem Cells: Development and Regeneration. BIOS Scientific Publishers. Oxford.

Abstract

  1. Huang WC, Ferris E, Cheng T, Hrndli CS, Gleason K, Tamminga C, Gregg C (2016). Non-genetic Allelic Effects in the Human Brain [Abstract]. Human Epigenetics & Disease. Keystone meeting. Seattle, WA, USA.

  2. Huang WC, Ferris E, Cheng T, Hrndli CS, Gleason K, Tamminga C, Wagner JD, Boucher KM, Christian JL, Gregg C (2016). Diverse Non-genetic Allele-Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain [Abstract]. Human Epigenetics & Disease. Keystone Meeting. Seattle, WA, USA.

Jeff Barson
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