Megan Mulligan, PhD

Education

• PhD Institution: University of Texas Austin, Molecular Biology
• Postdoctoral: UTHSC, Neurogenetics

Research Interests

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.

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.

Representative Publications

• Mulligan MK. Genetic Factors in Cannabinoid Use and Dependence. Adv Exp Med Biol. 2019;1162:129-150. doi: 10.1007/978-3-030-21737-2_7. Review. PubMed PMID: 31332737.
• Babbs RK, Beierle JA, Ruan QT, Kelliher JC, Chen MM, Feng AX, Kirkpatrick SL, Benitez FA, Rodriguez FA, Pierre JJ, Anandakumar J, Kumar V, Mulligan MK, Bryant CD. Cyfip1 Haploinsufficiency Increases Compulsive-Like Behavior and Modulates Palatable Food Intake in Mice: Dependence on Cyfip2 Genetic Background, Parent-of Origin, and Sex. G3 (Bethesda). 2019 Sep 4;9(9):3009-3022. doi: 10.1534/g3.119.400470. PubMed PMID: 31324746; PubMed Central PMCID: PMC6723122.
• Prins P, Smant G, Arends D, Mulligan MK, Williams RW, Jansen RC. Systems Genetics for Evolutionary Studies. Methods Mol Biol. 2019;1910:635-652. doi: 10.1007/978-1-4939-9074-0_21. PubMed PMID: 31278680.
• Parks C, Giorgianni F, Jones BC, Beranova-Giorgianni S, Moore Ii BM, Mulligan MK. Comparison and Functional Genetic Analysis of Striatal Protein Expression Among Diverse Inbred Mouse Strains. Front Mol Neurosci. 2019 May 24;12:128. doi: 10.3389/fnmol.2019.00128. eCollection 2019. PubMed PMID: 31178692; PubMed Central PMCID: PMC6543464.
• Terenina EE, Cavigelli S, Mormede P, Zhao W, Parks C, Lu L, Jones BC, Mulligan MK. Genetic Factors Mediate the Impact of Chronic Stress and Subsequent Response to Novel Acute Stress. Front Neurosci. 2019 May 21;13:438. doi: 10.3389/fnins.2019.00438. eCollection 2019. PubMed PMID: 31164799; PubMed Central PMCID: PMC6536627.
• Mulligan MK, Lu L, Cavigelli SA, Mormède P, Terenina E, Zhao W, Williams RW, Jones BC. Impact of Genetic Variation on Stress-Related Ethanol Consumption. Alcohol Clin Exp Res. 2019 Jul;43(7):1391-1402. doi: 10.1111/acer.14073. Epub 2019 May 21. PubMed PMID: 31034606.

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