Kristin L Patrick, Ph.D.

Associate Professor

kristin.patrick.1@vanderbilt.edu
Faculty Appointments
Associate Professor of Pathology, Microbiology and Immunology Associate Professor of Biochemistry
Education
Ph.D., Microbiology, Yale University, New Haven, ConnecticutB.A., Biochemistry, Hamilton College, Clinton, New York
Research Description
Broadly, my lab works to elucidate the molecular mechanisms of innate immune regulation in macrophages. Macrophage detection of pathogen- and damage-associated molecular patterns triggers complex signal transduction cascades that turn on expression of hundreds of cytokines, chemokines, and antimicrobial mediators. While a rapid and robust innate immune response is needed to limit infection, a response that is too strong carries risks (e.g., cytokine storm, autoimmunity, chronic inflammation, etc.). Therefore, macrophage gene expression needs to be tightly regulated. My lab works to implicate post-transcriptional regulatory mechanisms (e.g., pre-mRNA splicing, mRNA export, RNA decay/turnover, RNA localization etc.) in shaping inflammatory gene expression. We employ a multidisciplinary toolbox of protein and RNA biochemistry, transcriptomics, and microscopy-based approaches to tease apart pathways of interest in mechanistic detail. To date, we have identified several novel vulnerability nodes in the innate immune response that are controlled by the activities of RNA binding proteins (RBPs) in the SR and hnRNP families. By highlighting new and unexpected ways that RBPs balance innate immune responses, our work furthers our understanding of how inflammation can be dysregulated during infection and in a variety of human diseases.

My lab also collaborates with that of Dr. Robert Watson to investigate the Mycobacterium tuberculosis-macrophage host-pathogen interface, focusing on regulation of cytosolic innate immune sensing, the interplay between mitochondrial homeostasis and macrophage gene expression, and Mtb effector protein function.
Research Keywords
macrophage, innate immunity, bacteria, bacterial pathogenesis, RNA biology, splicing, biomolecular condensates, nucleus, gene expression, transcription, chromatin, imaging, infectious diseases, immunology, Mycobacterium tuberculosis,
Publications
Mabry CJ, Weindel CG, Stranahan LW, Martinez EL, VanPortfliet JJ, West AP, Patrick KL, Watson RO. Necrosis drives susceptibility to Mycobacterium tuberculosis in POLG mtDNA mutator mice. BioRxiv. 2024 Jul 7/22/2024; PMID: 39091776, PMCID: PMC11291070, PII: 2024.07.17.603991, DOI: 10.1101/2024.07.17.603991, ISSN: 2692-8205.

Weindel CG, Ellzey LM, Coleman AK, Patrick KL, Watson RO. LRRK2 kinase activity restricts NRF2-dependent mitochondrial protection in microglia. BioRxiv. 2024 Jul 7/13/2024; PMID: 39026883, PMCID: PMC11257505, PII: 2024.07.09.602769, DOI: 10.1101/2024.07.09.602769, ISSN: 2692-8205.

Cabello AL, Wells K, Peng W, Feng HQ, Wang J, Meyer DF, Noroy C, Zhao ES, Zhang H, Li X, Chang H, Gomez G, Mao Y, Patrick KL, Watson RO, Russell WK, Yu A, Zhong J, Guo F, Li M, Zhou M, Qian X, Kobayashi KS, Song J, Panthee S, Mechref Y, Ficht TA, Qin QM, de Figueiredo P. Brucella-driven host N-glycome remodeling controls infection. Cell Host Microbe [print-electronic]. 2024 Apr 4/10/2024; 32(4): 588-605.e9-605.e9. PMID: 38531364, PII: S1931-3128(24)00083-0, DOI: 10.1016/j.chom.2024.03.003, ISSN: 1934-6069.

Scott HM, Smith MH, Coleman AK, Armijo KS, Chapman MJ, Apostalo SL, Wagner AR, Watson RO, Patrick KL. Serine/arginine-rich splicing factor 7 promotes the type I interferon response by activating Irf7 transcription. Cell Rep [print-electronic]. 2024 Mar 3/26/2024; 43(3): 113816. PMID: 38393946, PMCID: PMC11056844, PII: S2211-1247(24)00144-X, DOI: 10.1016/j.celrep.2024.113816, ISSN: 2211-1247.

Azam S, Armijo KS, Weindel CG, Chapman MJ, Devigne A, Nakagawa S, Hirose T, Carpenter S, Watson RO, Patrick KL. The early macrophage response to pathogens requires dynamic regulation of the nuclear paraspeckle. Proc Natl Acad Sci U S A [print-electronic]. 2024 Feb 2/27/2024; 121(9): e2312587121. PMID: 38381785, PMCID: PMC10907238, DOI: 10.1073/pnas.2312587121, ISSN: 1091-6490.

Ellzey LM, Patrick KL, Watson RO. Mitochondrial reactive oxygen species: double agents in Mycobacterium tuberculosis infection. Curr Opin Immunol [print-electronic]. 2023 Oct; 84: 102366. PMID: 37453340, PMCID: PMC10711692, PII: S0952-7915(23)00085-7, DOI: 10.1016/j.coi.2023.102366, ISSN: 1879-0372.

Weindel CG, Ellzey LM, Martinez EL, Watson RO, Patrick KL. Gasdermins gone wild: new roles for GSDMs in regulating cellular homeostasis. Trends Cell Biol [print-electronic]. 2023 Sep; 33(9): 773-87. PMID: 37062616, PMCID: PMC10611448, PII: S0962-8924(23)00039-9, DOI: 10.1016/j.tcb.2023.02.007, ISSN: 1879-3088.

Wagner AR, Weindel CG, West KO, Scott HM, Watson RO, Patrick KL. SRSF6 balances mitochondrial-driven innate immune outcomes through alternative splicing of BAX. Elife. 2022 Nov 11/21/2022; 11: PMID: 36409059, PMCID: PMC9718523, PII: 82244, DOI: 10.7554/eLife.82244, ISSN: 2050-084X.

Weindel CG, Martinez EL, Zhao X, Mabry CJ, Bell SL, Vail KJ, Coleman AK, VanPortfliet JJ, Zhao B, Wagner AR, Azam S, Scott HM, Li P, West AP, Karpac J, Patrick KL, Watson RO. Mitochondrial ROS promotes susceptibility to infection via gasdermin D-mediated necroptosis. Cell [print-electronic]. 2022 Aug 8/18/2022; 185(17): 3214-3231.e23-3231.e23. PMID: 35907404, PMCID: PMC9531054, PII: S0092-8674(22)00790-5, DOI: 10.1016/j.cell.2022.06.038, ISSN: 1097-4172.

Wells KM, He K, Pandey A, Cabello A, Zhang D, Yang J, Gomez G, Liu Y, Chang H, Li X, Zhang H, Feng X, da Costa LF, Metz R, Johnson CD, Martin CL, Skrobarczyk J, Berghman LR, Patrick KL, Leibowitz J, Ficht A, Sze SH, Song J, Qian X, Qin QM, Ficht TA, de Figueiredo P. Brucella activates the host RIDD pathway to subvert BLOS1-directed immune defense. Elife. 2022 May 5/19/2022; 11: PMID: 35587649, PMCID: PMC9119680, PII: 73625, DOI: 10.7554/eLife.73625, ISSN: 2050-084X.

Sengupta S, West KO, Sanghvi S, Laliotis G, Agosto LM, Lynch KW, Tsichlis PN, Singh H, Patrick KL, Guerau-de-Arellano M. PRMT5 Promotes Symmetric Dimethylation of RNA Processing Proteins and Modulates Activated T Cell Alternative Splicing and Ca2+/NFAT Signaling. Immunohorizons. 2021 Oct 10/29/2021; 5(10): 884-97. PMID: 34716181, PMCID: PMC9377504, PII: immunohorizons.2100076, DOI: 10.4049/immunohorizons.2100076, ISSN: 2573-7732.

Vail KJ, da Silveira BP, Bell SL, Cohen ND, Bordin AI, Patrick KL, Watson RO. The opportunistic intracellular bacterial pathogen Rhodococcus equi elicits type I interferon by engaging cytosolic DNA sensing in macrophages. PLoS Pathog. 2021 Sep; 17(9): e1009888. PMID: 34473814, PMCID: PMC8443056, PII: PPATHOGENS-D-21-00708, DOI: 10.1371/journal.ppat.1009888, ISSN: 1553-7374.

Bell SL, Lopez KL, Cox JS, Patrick KL, Watson RO. Galectin-8 Senses Phagosomal Damage and Recruits Selective Autophagy Adapter TAX1BP1 To Control Mycobacterium tuberculosis Infection in Macrophages. MBio [print-electronic]. 2021 Aug 8/31/2021; 12(4): e0187120. PMID: 34225486, PMCID: PMC8406326, DOI: 10.1128/mBio.01871-20, ISSN: 2150-7511.

Ding S, Yang J, Feng X, Pandey A, Barhoumi R, Zhang D, Bell SL, Liu Y, da Costa LF, Rice-Ficht A, Watson RO, Patrick KL, Qin QM, Ficht TA, de Figueiredo P. Interactions between fungal hyaluronic acid and host CD44 promote internalization by recruiting host autophagy proteins to forming phagosomes. IScience. 2021 Mar 3/19/2021; 24(3): 102192. PMID: 33718841, PMCID: PMC7920835, PII: S2589-0042(21)00160-7, DOI: 10.1016/j.isci.2021.102192, ISSN: 2589-0042.

Patrick KL, Watson RO. Mitochondria: Powering the Innate Immune Response to Mycobacterium tuberculosis Infection. Infect Immun [electronic-print]. 2021 Mar 3/17/2021; 89(4): PMID: 33558322, PMCID: PMC8090963, PII: IAI.00687-20, DOI: 10.1128/IAI.00687-20, ISSN: 1098-5522.

Wagner AR, Scott HM, West KO, Vail KJ, Fitzsimons TC, Coleman AK, Carter KE, Watson RO, Patrick KL. Global Transcriptomics Uncovers Distinct Contributions From Splicing Regulatory Proteins to the Macrophage Innate Immune Response. Front Immunol. 2021; 12: 656885. PMID: 34305890, PMCID: PMC8299563, DOI: 10.3389/fimmu.2021.656885, ISSN: 1664-3224.

Hoffpauir CT, Bell SL, West KO, Jing T, Wagner AR, Torres-Odio S, Cox JS, West AP, Li P, Patrick KL, Watson RO. TRIM14 Is a Key Regulator of the Type I IFN Response during Mycobacterium tuberculosis Infection. J Immunol [print-electronic]. 2020 Jul 7/1/2020; 205(1): 153-67. PMID: 32404352, PMCID: PMC7313415, PII: jimmunol.1901511, DOI: 10.4049/jimmunol.1901511, ISSN: 1550-6606.

Weindel CG, Bell SL, Vail KJ, West KO, Patrick KL, Watson RO. LRRK2 maintains mitochondrial homeostasis and regulates innate immune responses to Mycobacterium tuberculosis. Elife. 2020 Feb 2/14/2020; 9: PMID: 32057291, PMCID: PMC7159881, PII: 51071, DOI: 10.7554/eLife.51071, ISSN: 2050-084X.

Antoine M, Patrick KL, Soret J, Duc P, Rage F, Cacciottolo R, Nissen KE, Cauchi RJ, Krogan NJ, Guthrie C, Gachet Y, Bordonné R. Splicing Defects of the Profilin Gene Alter Actin Dynamics in an S. pombe SMN Mutant. IScience [print-electronic]. 2020 Jan 1/24/2020; 23(1): 100809. PMID: 31927482, PMCID: PMC6957872, PII: S2589-0042(19)30555-3, DOI: 10.1016/j.isci.2019.100809, ISSN: 2589-0042.

West KO, Scott HM, Torres-Odio S, West AP, Patrick KL, Watson RO. The Splicing Factor hnRNP M Is a Critical Regulator of Innate Immune Gene Expression in Macrophages. Cell Rep. 2019 Nov 11/5/2019; 29(6): 1594-1609.e5-1609.e5. PMID: 31693898, PMCID: PMC6981299, PII: S2211-1247(19)31282-3, DOI: 10.1016/j.celrep.2019.09.078, ISSN: 2211-1247.

Patrick KL, Bell SL, Weindel CG, Watson RO. Exploring the "Multiple-Hit Hypothesis" of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat. Front Cell Infect Microbiol. 2019; 9: 138. PMID: 31192157, PMCID: PMC6546885, DOI: 10.3389/fcimb.2019.00138, ISSN: 2235-2988.

Patrick KL, Wojcechowskyj JA, Bell SL, Riba MN, Jing T, Talmage S, Xu P, Cabello AL, Xu J, Shales M, Jimenez-Morales D, Ficht TA, de Figueiredo P, Samuel JE, Li P, Krogan NJ, Watson RO. Quantitative Yeast Genetic Interaction Profiling of Bacterial Effector Proteins Uncovers a Role for the Human Retromer in Salmonella Infection. Cell Syst [print-electronic]. 2018 Sep 9/26/2018; 7(3): 323-338.e6-338.e6. PMID: 30077634, PMCID: PMC6160342, PII: S2405-4712(18)30277-1, DOI: 10.1016/j.cels.2018.06.010, ISSN: 2405-4712.

Nissen KE, Homer CM, Ryan CJ, Shales M, Krogan NJ, Patrick KL, Guthrie C. The histone variant H2A.Z promotes splicing of weak introns. Genes Dev. 2017 Apr 4/1/2017; 31(7): 688-701. PMID: 28446597, PMCID: PMC5411709, PII: 31/7/688, DOI: 10.1101/gad.295287.116, ISSN: 1549-5477.

Patrick KL, Bell SL, Watson RO. For Better or Worse: Cytosolic DNA Sensing during Intracellular Bacterial Infection Induces Potent Innate Immune Responses. J Mol Biol [print-electronic]. 2016 Aug 8/28/2016; 428(17): 3372-86. PMID: 27139640, PII: S0022-2836(16)30111-5, DOI: 10.1016/j.jmb.2016.04.030, ISSN: 1089-8638.

Patrick KL, Ryan CJ, Xu J, Lipp JJ, Nissen KE, Roguev A, Shales M, Krogan NJ, Guthrie C. Genetic interaction mapping reveals a role for the SWI/SNF nucleosome remodeler in spliceosome activation in fission yeast. PLoS Genet. 2015 Mar; 11(3): e1005074. PMID: 25825871, PMCID: PMC4380400, PII: PGENETICS-D-14-02840, DOI: 10.1371/journal.pgen.1005074, ISSN: 1553-7404.

Ryan CJ, Roguev A, Patrick K, Xu J, Jahari H, Tong Z, Beltrao P, Shales M, Qu H, Collins SR, Kliegman JI, Jiang L, Kuo D, Tosti E, Kim HS, Edelmann W, Keogh MC, Greene D, Tang C, Cunningham P, Shokat KM, Cagney G, Svensson JP, Guthrie C, Espenshade PJ, Ideker T, Krogan NJ. Hierarchical modularity and the evolution of genetic interactomes across species. Mol Cell. 2012 Jun 6/8/2012; 46(5): 691-704. PMID: 22681890, PMCID: PMC3380636, PII: S1097-2765(12)00444-3, DOI: 10.1016/j.molcel.2012.05.028, ISSN: 1097-4164.

Patrick KL, Shi H, Kolev NG, Ersfeld K, Tschudi C, Ullu E. Distinct and overlapping roles for two Dicer-like proteins in the RNA interference pathways of the ancient eukaryote Trypanosoma brucei. Proc Natl Acad Sci U S A [print-electronic]. 2009 Oct 10/20/2009; 106(42): 17933-8. PMID: 19815526, PMCID: PMC2764927, PII: 0907766106, DOI: 10.1073/pnas.0907766106, ISSN: 1091-6490.

Patrick KL, Luz PM, Ruan JP, Shi H, Ullu E, Tschudi C. Genomic rearrangements and transcriptional analysis of the spliced leader-associated retrotransposon in RNA interference-deficient Trypanosoma brucei. Mol Microbiol [print-electronic]. 2008 Jan; 67(2): 435-47. PMID: 18067542, PMCID: PMC2610267, PII: MMI6057, DOI: 10.1111/j.1365-2958.2007.06057.x, ISSN: 0950-382X.