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.
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.
Education History
Other Training |
Cold Spring Harbor Laboratory Integrative Statistical Analysis of Genomic Data |
Certificate |
---|---|---|
Other Training |
Cold Spring Harbor Laboratory Programming for Biology |
Certificate |
Postdoctoral Fellowship |
Harvard University Catherine Dulac Laboratory |
Postdoctoral Fellow |
Doctoral Training |
Hotchkiss Brain Institute, University of Calgary Neuroscience, Samuel Weiss Laboratory |
Ph.D. |
Undergraduate |
University of Lethbridge Biochemistry |
B.Sc. |
Selected Publications
- Bonthuis PJ, Steinwand S, Stacher Hrndli CN, Emery J, Huang WC, Kravitz S, Ferris E, Gregg C (2020). Noncanonical genomic imprinting in the monoamine system determines naturalistic foraging and brain-adrenal axis functions. Cell Rep, 38(10), 110500.
- Tollis M, Ferris E, Campbell MS, Harris VK, Rupp SM, Harrison TM, Kiso WK, Schmitt DL, Garner MM, Aktipis CA, Maley CC, Boddy AM, Yandell M, Gregg C, Schiffman JD, Abegglen LM (2021). Elephant Genomes Reveal Accelerated Evolution in Mechanisms Underlying Disease Defenses. Mol Biol Evol, 38(9), 3606-3620.
- Kravitz SN, Gregg C (2019). New subtypes of allele-specific epigenetic effects: implications for brain development, function and disease. [Review]. Curr Opin Neurobiol, 59, 69-78.
- Ferris E, Gregg C (2019). Parallel Accelerated Evolution in Distant Hibernators Reveals Candidate Cis Elements and Genetic Circuits Regulating Mammalian Obesity. Cell Rep, 29(9), 2608-2620.e4.
- Stacher Hrndli CN, Wong E, Ferris E, Bennett K, Steinwand S, Rhodes AN, Fletcher PT, Gregg C (2018). Complex Economic Behavior Patterns Are Constructed from Finite, Genetically Controlled Modules of Behavior. Cell Rep, 28(7), 1814-1829.e6.
- Huang WC, Bennett K, Gregg C (2018). Epigenetic and Cellular Diversity in the Brain through Allele-Specific Effects. [Review]. Trends Neurosci, 41(12), 925-937.
- Ferris E, Abegglen LM, Schiffman JD, Gregg C (2017). Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance. Cell Rep, 22(10), 2742-2755.
- 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.
- Gregg C (2017). The emerging landscape of in vitro and in vivo epigenetic allelic effects. [Review]. F1000Res, 6, 2108.
- Gregg C (2017). The emerging landscape of in vitro and in vivo epigenetic allelic effects. [Review]. F1000Res, 6(2108).
- Jacobi AM, Rettig GR, Turk R, Collingwood MA, Zeiner SA, Quadros RM, Harms DW, Bonthuis PJ, Gregg C, Ohtsuka M, Gurumurthy CB, Behlke MA (2017). Simplified CRISPR tools for efficient genome editing and streamlined protocols for their delivery into mammalian cells and mouse zygotes. Methods, 121-122, 16-28.
- 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.e7.
- 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.
- Huang WC, Ferris E, Gregg C (2017). Algorithm to identify non-genetic allelic effects using RNASeq. U.S. Patent No. Provisional. Washington, D.C.:U.S. Patent and Trademark Office.
- 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.
- 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.
- Gregg C, Ferris E (2016). Methods for Detecting Rapidly Processed Introns to Evaluate Allelic Expression. U.S. Patent No. 62/494,162 (July 29, 2016). Washington, D.C.:U.S. Patent and Trademark Office.
- 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.
- McKenna S, Meyer M, Gregg C, Gerber S (2015). s-CorrPlot: An Interactive Scatterplot for Exploring Correlation. J Comput Graph Stat, 25(2,2016).
- 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.
- Gregg C (2014). Known unknowns for allele-specific expression and genomic imprinting effects. [Review]. F1000Res, 4(6), 75-77.
- 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.
- 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.
- Gregg C (2010). Eppendorf winner. Parental Control Over The Brain. [Review]. Science, 330(6005), 770-1.
- 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.
- 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.
- Gregg C (2009). Pregnancy, prolactin and white matter regeneration. [Review]. J Neurol Sci, 285(1-2), 22-7.
- Gregg C, Weiss S (2009). Pregnancy-induced oligodendrocyte precursor cell proliferation regulated by prolactin. U.S. Patent No. 7,534,765. Washington, D.C.:U.S. Patent and Trademark Office.
- Weiss S, Gregg C, Davidoff A, Tucker J (2009). Continuous dosing regimes for neural stem cell proliferating agents and neural stem cell differentiating agents. U.S. Patent No. 0081205 A1. Washington, D.C.:U.S. Patent and Trademark Office.
- Gregg C (2009). Pregnancy, Prolactin and White Matter Regeneration. 285(1-2), 22-7.
- Gregg C (2009). Pregnancy, Prolactin and White Matter Regeneration. [Review]. 285(1-2), 22-7.
- Weiss S, Gregg C, Davidoff A, Tucker J (2008). Dosing regimes for neural stem cell proliferating agents for the treatment of neurological disorders. U.S. Patent No. 0039389 A1. Washington, D.C.:U.S. Patent and Trademark Office.
- 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.
- 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.
- 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.
- Weiss S, Gregg C (2006). Production of radial glial cells. U.S. Patent No. 7,033,995 B2. Washington, D.C.:U.S. Patent and Trademark Office.
- 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.
- 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.
- Weiss S, Enwere E, Andersen L, Gregg C (2005). Pheromones and the lutenizing hormone for inducing proliferation of neural stem cells and neurogenesis. U.S. Patent No. 0245436 A1. Washington, D.C.:U.S. Patent and Trademark Office.
- 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.
- 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.
- 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.
- 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.
- Gregg CT, Chojnacki AK, Weiss S (2002). Radial glial cells as neuronal precursors: the next generation? [Review]. J Neurosci Res, 69(6), 708-13.
- Gregg CT, Shingo T, Weiss S (2001). Neural stem cells of the mammalian forebrain. [Review]. Symp Soc Exp Biol, (53), 1-19.
- 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.
Global Impact
Education History
Type | School | Degree |
---|---|---|
Doctoral Training | Hotchkiss Brain Institute, University of Calgary Neuroscience, Samuel Weiss Laboratory |
Ph.D. |
Undergraduate | University of Lethbridge Biochemistry |
B.Sc. |