MULLIGAN, MEGAN K.

Assistant Professor
Genetics,Genomics&Informatics

Office: 409 TRANSLATIONAL RESEARCH BUILDING
71 SOUTH MANASSAS
MEMPHIS TN 38163
Tel: (901) 448-3548
mkmulligan@uthsc.edu

Education

  • PostDoc, UTHSC, Neurogenetics
  • Ph.D., University of Texas Austin, Molecular Biology
  • B.A., University of California Santa Cruz, Biology and Psychology

Research Keywords

 GABRA2, GABA-A Receptors, Brain, Neuroscience, Behavior, Addicition, Genetics, Cannabinoids, Cannabis, THC, Alcohol

My Current CV

Research Description

Developing a Reduced Complexity Cross for Efficient Behavioral Genetics. There are 40 to 50 million validated reference SNPs for human and mouse. This level of genomic complexity poses genuine challenges for the identification of polymorphisms that control trait variation and for modeling complex gene-gene and gene-environment interactions. To facilitate identification of candidate genes and variants that underlie behavior, my lab and several collaborators are leveraging reduced complexity crosses (RCCs) with low levels of genetic diversity but moderate to high levels of phenotypic diversity by crossing closely related substrains. Separation and maintenance of inbred rodent colonies at different institutions leads to genetic drift over time and the creation of non-isogenic subpopulations and substrains. Mouse and rat substrain colonies are a valuable resource for studying the impact of naturally occurring mutations on complex traits and can greatly facillitate candidate gene identification relative to more complex crosses.

Dissecting the Role of Genetic Variants in the GABA-A Receptor Alpha 2 Subunit (Gabra2). GABA-A receptors are critical for inhibitory neurotransmission and play an important role in brain development, function, and disease. In human populations variants in the α2 subunit (GABRA2) have been linked to alcohol dependence, subjective effect of alcohol, alterations in brain circuitry, impulsivity, and other substance use disorders. In collaboration with several differnt research groups, my lab identified a mutation that resulted in marked reduction of brain Gabra2 mRNA and protein expression in C57BL/6J and other derivative mouse strains. The mutation is a single base pair non-coding deletion located adjacent to an exon within a splice acceptor site. Repair of the deletion by CRISPR-Cas9 editing restores transcript and protein levels. Variation in Gabra2 is associated with sensitivity to alcohol, anxiety, fear memory, and acute sensitivty to methamphetamine and alcohol. Discovery of this functional non-coding variant in mouse may inform identification of causal variants in human populations and will be useful for investigating trait variation associated with the α2 subunit in these populations.

Stress and the Genome. Early life stress, chronic stress, and even acute exposure to stress are highly comorbid with a variety of physical and mental health outcomes in human populations. The exact genetic and epigenetic mechanisms driving these relationships are not well understood. In collaboration with several groups at UTHSC, my lab uses different genetic mouse populations to identify gene variants that control stress reactivity and mediate alterations in alcohol consumption in response to stress and to identify common molecular pathways mediating stress induced alcohol consumption. Overarching goals are to identify individuals, based on genotype, that predict negative outcomes after stress exposure.

The Genetics of Cannabinoid Response. Recent policy changes in the United States related to the legalization of cannabis and cannabinoids for medicinal and/or recreational purposes is expected to increase the prevalence of cannabinoid use. Concomitant with increased use is a spectrum of adverse health consequences, including abuse and dependence. Recently, my lab has started to characterize inbred mouse strain differences in initial and chronic response to cannabinoids with the overaching goal of identifying gene variants that mediate variation in initial sensitivity and rapid tolerance to cannabinoids. This includes physiological responses to the main psychoactive ingredient in cannabis, Δ9-tetrahydrocannabinol (THC), and a major non-psychoactive component, cannabindiol (CBD). We are also interested in exploring genetic factors mediating withdrawal from cannabinoids and the influence of prenatal THC exposure on adolescent development. 

Research Interest/Specialty

The goal of my research is to use a holistic systems approach, including genetic models, new molecular biology tools, and diverse bioinformatics resources in order to identify mechanisms by which genetic and environmental variation influence DNA modification, gene and protein expression, and neuronal function to modulate complex behavior and disease states.

Publications

  1. Hook, M, Xu, F, Terenina, E, Zhao, W, Starlard-Davenport, A, Mormede, P, Jones, BC, Mulligan, MK, Lu, L. Exploring the involvement of Tac2 in the mouse hippocampal stress response through gene networking. Gene, 696, 176-185, 2019.
  2. Bryant, CD, Bagdas, D, Goldberg, LR, Khalefa, T, Reed, ER, Kirkpatrick, SL, Kelliiher, JC, Chen, MM, Johnson, WE, Mulligan, MK, Damaj, MI. C57BL/6 substrain differences in inflammatory and neuropathic nociception and genetic mapping of a major quantitative trait locus underlying acute thermal nociception. Mol Pain, 1744806918825046, 2019.
  3. Babbs, RK, Kelliher, JC, Scotellaro, JL, Luttik, KP, Mulligan, MK, Bryant, CD. Genetic differences in the behavioral organization of binge eating, conditioned food reward, and compulsive-like eating in C57BL/6J and DBA/2J strains. Physiol Behav, 197, 51-66, 2018.
  4. Nowak, TS, Mulligan, MK. Impact of C57BL/6 substrain on sex-dependent differences in mouse stroke models. Neurochem Int, 2018.
  5. Farris, SP, Riley, BP, Williams, RW, Mulligan, MK, Miles, MF, Lopez, MF, Hitzemann, R, Iancu, OD, Colville, A, Walter, NAR, Darakjian, P, Oberbeck, DL, Daunais, JB, Zheng, CL, Searles, RP, McWeeney, SK, Grant, KA, Mayfield, RD. Cross-species molecular dissection across alcohol behavioral domains. Alcohol, 72, 19-31, 2018.
  6. Mulligan, MK, Zhao, W, Dickerson, M, Arends, D, Prins, P, Cavigelli, SA, Terenina, E, Mormede, P, Lu, L, Jones, BC. Genetic Contribution to Initial and Progressive Alcohol Intake Among Recombinant Inbred Strains of Mice. Front Genet, 9, 370, 2018.
  7. Lim, PH, Shi, G, Wang, T, Jenz, ST, Mulligan, MK, Redei, EE, Chen, H. Genetic Model to Study the Co-Morbid Phenotypes of Increased Alcohol Intake and Prior Stress-Induced Enhanced Fear Memory. Front Genet, 9, 566, 2018.
  8. Mulligan, MK, Mozhui, K, Pandey, AK, Smith, ML, Gong, S, Ingels, J, Miles, MF, Lopez, MF, Lu, L, Williams, RW. Genetic divergence in the transcriptional engram of chronic alcohol abuse: A laser-capture RNA-seq study of the mouse mesocorticolimbic system. Alcohol, 58, 61-72, 2017.
  9. Baker, JA, Li, J, Zhou, D, Yang, M, Cook, MN, Jones, BC, Mulligan, MK, Hamre, KM, Lu, L. Analyses of differentially expressed genes after exposure to acute stress, acute ethanol, or a combination of both in mice. Alcohol, 58, 139-151, 2017.
  10. Zhao, L, Mulligan, MK, Nowak, TS. Substrain- and sex-dependent differences in stroke vulnerability in C57BL/6 mice. J Cereb Blood Flow Metab, 271678X17746174, 2017.
  11. Mulligan, MK, Mozhui, K, Prins, P, Williams, RW. GeneNetwork: A Toolbox for Systems Genetics. Methods Mol Biol, 1488, 75-120, 2016.
  12. Lu, L, Pandey, AK, Houseal, MT, Mulligan, MK. The Genetic Architecture of Murine Glutathione Transferases. PLoS One, 11 (2), e0148230, 2016.
  13. Wang, X, Pandey, AK, Mulligan, MK, Williams, EG, Mozhui, K, Li, Z, Jovaisaite, V, Quarles, LD, Xiao, Z, Huang, J, Capra, JA, Chen, Z, Taylor, WL, Bastarache, L, Niu, X, Pollard, KS, Ciobanu, DC, Reznik, AO, Tishkov, AV, Zhulin, IB, Peng, J, Nelson, SF, Denny, JC, Auwerx, J, Lu, L, Williams, RW. Joint mouse-human phenome-wide association to test gene function and disease risk. Nat Commun, 7, 10464, 2015.
  14. Shin, DL, Pandey, AK, Ziebarth, JD, Mulligan, MK, Williams, RW, Geffers, R, Hatesuer, B, Schughart, K, Wilk, E. Segregation of a spontaneous Klrd1 (CD94) mutation in DBA/2 mouse substrains. G3 (Bethesda), 5 (2), 235-9, 2015.
  15. Mulligan, MK, Dubose, C, Yue, J, Miles, MF, Lu, L, Hamre, KM. Expression, covariation, and genetic regulation of miRNA Biogenesis genes in brain supports their role in addiction, psychiatric disorders, and disease. Front Genet, 4, 126, 2013.
  16. Williams, RW, Mulligan, MK. Genetic and molecular network analysis of behavior. Int Rev Neurobiol, 104, 135-57, 2012.
  17. Wang, X, Mozhui, K, Li, Z, Mulligan, MK, Ingels, JF, Zhou, X, Hori, RT, Chen, H, Cook, MN, Williams, RW, Lu, L. A promoter polymorphism in the Per3 gene is associated with alcohol and stress response. Transl Psychiatry, 2, e73, 2012.
  18. Mozhui, K, Wang, X, Chen, J, Mulligan, MK, Li, Z, Ingles, J, Chen, X, Lu, L, Williams, RW. Genetic regulation of Nrxn1 [corrected] expression: an integrative cross-species analysis of schizophrenia candidate genes. Transl Psychiatry, 1, e25, 2012.
  19. Boughter, JD, Mulligan, MK, St John, SJ, Tokita, K, Lu, L, Heck, DH, Williams, RW. Genetic control of a central pattern generator: rhythmic oromotor movement in mice is controlled by a major locus near Atp1a2. PLoS One, 7 (5), e38169, 2012.
  20. Mulligan, MK, Wang, X, Adler, AL, Mozhui, K, Lu, L, Williams, RW. Complex control of GABA(A) receptor subunit mRNA expression: variation, covariation, and genetic regulation. PLoS One, 7 (4), e34586, 2012.
  21. Mulligan, MK, Rhodes, JS, Crabbe, JC, Mayfield, RD, Harris, RA, Ponomarev, I. Molecular profiles of drinking alcohol to intoxication in C57BL/6J mice. Alcohol Clin Exp Res, 35 (4), 659-70, 2011.
  22. Li, Z, Mulligan, MK, Wang, X, Miles, MF, Lu, L, Williams, RW. A transposon in Comt generates mRNA variants and causes widespread expression and behavioral differences among mice. PLoS One, 5 (8), e12181, 2010.
  23. Mulligan, MK, Ponomarev, I, Boehm, SL, Owen, JA, Levin, PS, Berman, AE, Blednov, YA, Crabbe, JC, Williams, RW, Miles, MF, Bergeson, SE. Alcohol trait and transcriptional genomic analysis of C57BL/6 substrains. Genes Brain Behav, 7 (6), 677-89, 2008.
  24. Mulligan, MK, Ponomarev, I, Hitzemann, RJ, Belknap, JK, Tabakoff, B, Harris, RA, Crabbe, JC, Blednov, YA, Grahame, NJ, Phillips, TJ, Finn, DA, Hoffman, PL, Iyer, VR, Koob, GF, Bergeson, SE. Toward understanding the genetics of alcohol drinking through transcriptome meta-analysis. Proc Natl Acad Sci U S A, 103 (16), 6368-73, 2006.