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

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, I developed a reduced complexity cross (RCC) with low levels of genetic diversity but moderate to high levels of phenotypic diversity by crossing B6J and C57BL/6NJ (B6NJ) substrains. Separation and maintenance of inbred mouse colonies at different institutions lead to genetic drift over time and the creation of non-isogenic subpopulations. These substrain colonies are a valuable resource for studying the impact of naturally occurring mutations on complex traits. For example, the parental B6J and B6NJ mice used to generate my RCC F2 progeny have been separated and maintained at different breeding facilities since 1951. Despite a similar genetic background, these substrains demonstrate marked differences in addiction, metabolic, and behavioral traits.

Dissecting the Role of Genetic Variants in the GABA-A Receptor Alpha 2 Subunit (Gabra2). Genetic variation at the GABRA2 locus is associated with alcohol dependence, early life stress and addiction susceptibility, impulsivty, and differences in brain activity. I am using a combination of mouse models (knockout, CRISPR gene editing, and naturally occuring mutations) to evaluate the effects of variation in Gabra2 levels with the goal of better understanding the consequences of GABRA2 variation in human 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. I use 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.

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. Lu, L, Pandey, AK, Houseal, MT, Mulligan, MK. The Genetic Architecture of Murine Glutathione Transferases. PLoS One, 11 (2), e0148230, 2016.
  2. 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.
  3. 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.
  4. 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.
  5. Williams, RW, Mulligan, MK. Genetic and molecular network analysis of behavior. Int Rev Neurobiol, 104, 135-57, 2012.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.