Aldons J. Lusis, Ph.D.

Distinguished Professor

310-825-1359

MRL 3-730

Website

Affiliations

Professor, Medicine, Microbiology, Immunology & Molecular Genetics, Human Genetics
Member, Genetics & Genomics GPB Home Area, JCCC Cancer and Stem Cell Biology Program Area, Molecular, Cellular & Integrative Physiology GPB Home Area, Cardiology.

Research Interests

Over the past two decades, our studies have focused on common, complex forms of cardiovascular/metabolic disorders, including atherosclerosis, fatty liver disease, and, more recently, heart failure.  We have used population-based approaches in both animal models and humans as well as experimental studies in mice. Human genome-wide association studies in large human populations have revolutionized our understanding of common diseases, but in addition to the identification of causal genes we are interested an understanding of the higher order interactions. To dissect such interactions, we use a systems biology perspective, integrating clinical trait phenotypes with genetic, epigenetic, transcriptomic, proteomic, and metabolomic high-throughput data.  Our primary contribution during the early 2000s was to help pioneer the approach which we term “systems genetics”, the integration of clinical and molecular data in mouse or human cohorts using statistical approaches, including causal and network modeling.

To model common human genetic variation under specific environmental conditions, we have developed a reference resource, called to Hybrid Mouse Diversity Panel (HMDP), that consists of a panel of about 100 well characterized inbred strains of mice. As compared to human studies, the panel has the advantage of replication, access to relevant tissues and control of environmental factors. The panel has now been extensively characterized for clinical traits and multiple high throughput “omics” phenotypes. To complement the studies in mice, we investigate publicly available data and participate in studies of well characterized human cohorts, including METSIM and STARNET.

Biography

Jake Lusis received his Ph.D. in Biophysics from Oregon State University and a postdoctoral fellowship with Kenneth Paigen in the Molecular Biology Department, Roswell Park Memorial Institute, Buffalo, NY. Since 1979, he has been on the faculty at the University of California, Los Angeles, where he is presently Professor in the Department of Microbiology, Immunology and Molecular Genetics, the Department of Medicine, and the Department of Human Genetics. He has served on advisory panels for the National Institutes of Health, the American Heart Association, and various private companies and organizations. Presently, he serves on the Board of Scientific Counselors, NHLBI. Among his awards are the Bristol-Myers Squibb Award for Distinguished Achievement in Research, the American Heart Association Duff Award, and the NAVBO Benditt Award.

Publications

Wang YC, Koay YC, Pan C, Zhou Z, Tang W, Wilcox J, Li XS, Zagouras A, Marques F, Allayee H, Rey FE, Kaye DM, O’Sullivan JF, Hazen SL, Cao Y, Lusis AJ. Indole-3-Propionic Acid Protects Against Heart Failure With Preserved Ejection Fraction. Circ Res. 2024; 134:371-389.

Kurt Z, Cheng J, McQuillen CN, Saleem Z, Hsu N, Jiang N, Barrere-Cain R, Pan C, Franzen O, Koplev S, Wang S, Bjorkegren J, Lusis AJ, Blencowe M, Yang X.  (2023)  Shared and distinct pathways and networks genetically linked to coronary artery disease between human and mouse.  eLife, 2023; 12:RP88266

Chella Krishnan K, El Hachem EJ, Keller MP, Patel SG, Carroll L, Vegas AD, Gerdes Gyuricza I, Light C, Cao Y, Pan C, Kaczor-Urbanowicz KE, Shravah V, Anum D, Pellegrini M, Lee CF, Seldin MM, Rosenthal NA, Churchill GA, Attie AD, Parker B, James DE, Lusis AJ.   Genetic architecture of heart mitochondrial proteome influencing cardiac hypertrophy.  eLife. 2023; 12:e82619

Wang YC, Cao Y, Pan C, Zhou Z, Yang L, Lusis AJ.  Intestinal cell type-specific communication networks underlie homeostasis and response to Western diet. J Exp Med. 2023; 220:e20221437

Cao Y, Wang Y, Zhou Z, Pan C, Jiang L, Zhou Z, Meng Y, Charugundla S, Li T, Allayee H, Seldin MM, Lusis AJ.  Liver-heart crosstalk mediated by coagulation factor XI (F11) protects against heart failure.  Science. 2022; 377:1399-1406.

Cao Y, Vergnes L, Wang YC, Pan C, Chella Krishnan K, Moore TM, Rosa-Garrido M, Kimball TH, Zhou Z, Charugundla S, Rau CD, Seldin MM, Wang J, Wang Y, Vondriska TM, Reue K, Lusis AJ.  Sex differences in heart mitochondria regulate diastolic dysfunction. Nat Commun. 2022; 13:3850.

Björkegren JLM, Lusis AJ.  (2022)  Atherosclerosis: Recent developments. Cell. 2022; 185:1630-1645.

Cao Y, Pan C, Wang YC, Zhou Z, Jedian V, Meng Y, Campbell G, Guardino K, Li C, Wang J, Lusis AJ.  (2022)  Identification of DNA damage repair enzyme Ascc2 as causal for heart failure with preserved ejection fraction. Circulation. 2022; 145:1102-1104

Koplev S, Seldin M, Sukhavasi K, Ermel R, Pang S, Zeng L, Bankier S, Di Narzo A, Cheng H, Meda V, Ma A, Talukdar H, Cohain A, Amadori L, Argmann C, Houten SM, Franzén O, Mocci G, Meelu OA, Ishikawa K, Whatling C, Jain A, Jain RK, Gan L, Giannarelli C, Roussos P, Hao K, Schunkert H, Michoel T, Ruusalepp A, Schadt EE, Kovacic JC, Lusis AJ, Björkegren JLM.  A mechanistic framework for cardiometabolic and coronary artery diseases. Nat Cardiovasc Res.  2022; 1:85-100.

Chella Krishnan K, Vergnes L, Acín-Pérez R, Stiles L, Shum M, Ma L, Mouisel E, Pan C, Moore TM, Péterfy M, Romanoski CE, Reue K, Björkegren JLM, Laakso M, Liesa M, Lusis AJ.  Sex-specific genetic regulation of adipose mitochondria and metabolic syndrome by Ndufv2.  Nat Metab. 2021; 3:1552-1568.

Sinha SK, Miikeda A, Fouladian Z, Mehrabian M, Edillor C, Shih D, Zhou Z, Paul MK, Charugundla S, Davis RC, Rajavashisth TB, Lusis AJ.  Local M-CSF (macrophage colony-stimulating factor) expression regulates macrophage proliferation and apoptosis in atherosclerosis.  Arterioscler Thromb Vasc Biol.  2020; 41:220-233

Yokota T, McCourt J, Ma F, Ren S, Li S, Kim TH, Kurmangaliyev YZ, Nasiri R, Ahadian S, Nguyen T, Tan XHM, Zhou Y, Wu R, Rodriguez A, Cohn W, Wang Y, Whitelegge J, Ryazantsev S, Khademhosseini A, Teitell MA, Chiou PY, Birk DE, Rowat AC, Crosbie RH, Pellegrini M, Seldin M, Lusis AJ, Deb A.  Type V collagen in scar tissue regulates the size of scar after heart injury.  Cell. 2020; 182:545-562

Seldin M, Yang X, Lusis AJ.  Systems genetics applications in metabolism research.  Nat Metab. 2019; 1:1038-1050

Shih DM, Zhu W, Schugar RC, Meng Y, Jia X, Miikeda A, Wang Z, Zieger M, Lee R, Graham M, Allayee H, Cantor RM, Mueller C, Brown JM, Hazen SL, Lusis AJ.  Genetic deficiency of flavin-containing monooxygenase-3 (Fmo3) protects against thrombosis but has only a minor effect on plasma lipid levels.  Arterioscler Thromb Vasc Biol. 2019; 39:1045-1054

Norheim F, Hasin-Brumshtein Y, Vergnes L, Chella Krishnan K, Pan C, Seldin MM, Hui ST, Mehrabian M, Zhou Z, Gupta S, Parks BW, Walch A, Reue K, Hofmann SM, Arnold AP, Lusis AJ.  Gene-by-sex interactions in mitochondrial functions and cardio-metabolic traits.  Cell Metab. 2019; 29:932-949

Kasahara K, Krautkramer KA, Org E, Romano KA, Kerby RL, Vivas EI, Mehrabian M, Denu JM, Bäckhed F, Lusis AJ, Rey FE.  Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model.  Nat Microbiol.  2018; 3:1461-1471

Erbilgin A, Seldin MM, Wu X, Mehrabian M, Zhou Z, Qi H, Dabirian KS, Sevag Packard RR, Hsieh W, Bensinger SJ, Sinha S, Lusis AJ.  Transcription factor Zhx2 deficiency reduces atherosclerosis and promotes macrophage apoptosis in mice.  Arterioscler Thromb Vasc Biol.  2018; 38:2016–2027

Hui ST, Kurt Z, Tuominen I, Norheim F, Davis RC, Pan C, Dirks DL, Magyar CE, French SW, Chella Krishnan K, Sabir S, Campos-Pérez F, Méndez-Sánchez N, Macías-Kauffer L, León-Mimila P, Canizales-Quinteros S, Yang X, Beaven SW, Huertas-Vazquez A, Lusis AJ.  The genetic architecture of diet-induced hepatic fibrosis in mice.  Hepatology. 2018; 68:2182-2196.

Seldin MM, Koplev S, Rajbhandari P, Vergnes L, Rosenberg GM, Meng Y, Pan C, Phuong TMN, Gharakhanian R, Che N, Mäkinen S, Shih DM, Civelek M, Parks BW, Kim ED, Norheim F, Chella Krishnan K, Hasin-Brumshtein Y, Mehrabian M, Laakso M, Drevon CA, Koistinen HA, Tontonoz P, Reue K, Cantor RM, Björkegren JLM, Lusis AJ.  A strategy for discovery of endocrine interactions with application to whole-body metabolism.  Cell Metab.  2018; 27:1138-1155

Chella Krishnan K, Kurt Z, Barrere-Cain R, Sabir S, Das A, Floyd R, Vergnes L, Zhao Y, Che N, Charugundla S, Qi H, Zhou Z, Meng Y, Pan C, Seldin MM, Norheim F, Hui S, Reue K, Lusis AJ, Yang X.  Integration of multi-omics data from Mouse Diversity Panel highlights mitochondrial dysfunction in non-alcoholic fatty liver disease.  Cell Syst. 2018; 6:103-115

Patterson M, Barske L, Van Handel B, Rau CD, Gan P, Sharma A, Parikh S, Denholtz M, Huang Y, Yamaguchi Y, Shen H, Allayee H, Crump JG, Force TI, Lien CL, Makita T, Lusis AJ, Kumar SR, Sucov HM.  (2017)  Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration. Nat Genet. 2017; 49:1346-1353

Hasin Y, Seldin M, Lusis A.  Multi-omics approaches to disease.  Genome Biol. 2017; 18:83

Civelek M, Wu Y, Pan C, Raulerson CK, Ko A, He A, Tilford C, Saleem NK, Stančáková A, Scott LJ, Fuchsberger C, Stringham HM, Jackson AU, Narisu N, Chines PS, Small KS, Kuusisto J, Parks BW, Pajukanta P, Kirchgessner T, Collins FS, Gargalovic PS, Boehnke M, Laakso M, Mohlke KL, Lusis AJ.  (2017)  Genetic regulation of adipose gene expression and cardio-metabolic traits.  Am J Hum Genet. 2017; 100:428-443

Pillai IC, Li S, Romay M, Lam L, Lu Y, Huang J, Dillard N, Zemanova M, Rubbi L, Wang Y, Lee J, Xia M, Liang O, Xie YH, Pellegrini M, Lusis AJ, Deb A.  Cardiac fibroblasts adopt osteogenic fates and can be targeted to attenuate pathological heart calcification. Cell Stem Cell. 2017; 20:218-232

von Scheidt M, Zhao Y, Kurt Z, Pan C, Zeng L, Yang X, Schunkert H, Lusis AJ.  Applications and limitations of mouse models for understanding human atherosclerosis. Cell Metab. 2016; 25:248-261

Rau CD, Romay MC, Tuteryan M, Wang JJ, Santolini M, Ren S, Karma A, Weiss JN, Wang Y, Lusis AJ.  (2017)  Systems genetics approach identifies gene pathways and Adamts2 as drivers of isoproterenol-induced cardiac hypertrophy and cardiomyopathy in mice. Cell Systems. 2016; 4:121-128

Wang JJ, Rau C, Avetisyan R, Ren S, Romay MC, Stolin G, Gong KW, Wang Y, Lusis AJ.  Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model. PLoS Genetics. 2016; 12(7): e1006038.

Bennett BJ, Davis RC, Civelek M, Orozco L, Wu J, Qi H, Pan C, Packard RR, Eskin E, Yan M, Kirchgessner T, Wang Z, Li X, Gregory JC, Hazen SL, Gargalovic PS, Lusis AJ.  Correction: Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains. PLoS Genetics. 2016; 12(3): e1005913.

Hui ST, Parks BW, Org E, Norheim F, Che N, Pan C, Castellani LW, Charugundla S, Dirks DL, Psychogios N, Neuhaus I, Gerszten RE, Kirchgessner T, Gargalovic PS, Lusis AJ.   The genetic architecture of NAFLD among inbred strains of mice. eLife. 2015; 4: e05607.

Parks BW, Sallam T, Mehrabian M, Psychogios N, Hui ST, Norheim F, Castellani LW, Rau CD, Pan C, Phun J, Zhou Z, Yang WP, Neuhaus I, Gargalovic PS, Kirchgessner TG, Graham M, Lee R, Tontonoz P, Gerszten RE, Hevener AL, Lusis AJ.  Genetic architecture of insulin resistance in the mouse. Cell Metabolism. 2015; 21(2): 334-46.

Parks BW, Nam E, Org E, Kostem E, Norheim F, Hui ST, Pan C, Civelek M, Rau CD, Bennett BJ, Mehrabian M, Ursell LK, He A, Castellani LW, Zinker B, Kirby M, Drake TA, Drevon CA, Knight R, Gargalovic P, Kirchgessner T, Eskin E, Lusis AJ.  Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice. Cell Metabolism. 2013; 17(1): 141-52.

Bennett BJ, Vallim TQ, Wang Z, Shih DM, Meng Y, Gregory J, Allayee H, Lee R, Graham M, Crooke R, Edwards PA, Hazen S, Lusis AJ.  Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metabolism. 2013; 17(1): 49-60.

Orozco LD, Bennett BJ, Farber CR, Ghazalpour A, Pan A, Che N, Wen P, Qi HX, Mutukulu A, Siemers N, Neuhaus I, Yordanova R, Gargalovic P, Pellegrini M, Kirchgessner T, Lusis AJ. Unraveling inflammatory responses using systems genetics and gene-environment interactions in macrophages. Cell. 2012; 151(3): 658-70.

Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL.  Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011; 472(7341): 57-63.

Bennett BJ, Farber CR, Orozco L, Kang HM, Ghazalpour A, Siemers N, Neubauer M, Neuhaus I, Yordanova R, Guan B, Truong A, Yang W, He A, Kayne P, Gargalovic P, Kirchgessner T, Pan C, Castellani L, Kostem E, Furlotte N, Drake TA, Eskin E, Lusis AJ.  A high-resolution association mapping panel for the dissection of complex traits in mice. Genome Research. 2010; 20(2): 281-90.

Schadt E.E., Lamb J., Yang X., Zhu J., Edwards S., Guhathakurta D., Sieberts S.K., Monks S., Reitman M., Zhang C., Lum P.Y., Leonardson A., Thieringer R., Metzger J.M., Yang L., Castle J., Zhu H., Kash S.F., Drake T.A., Sachs A., Lusis AJ.  An integrative genomics approach to infer causal associations between gene expression and disease. Nature Genetics. 2005; 37(7): 710-7.

Bodnar J.S., Chatterjee A., Castellani L.W., Ross D.A., Ohmen J., Cavalcoli J., Wu C., Dains K.M., Catanese J., Chu M., Sheth S.S., Charugundla K., Demant P., West D.B., de Jong P., Lusis AJ.   Positional cloning of the combined hyperlipidemia gene Hyplip1. Nature Genetics. 2002; 30(1): 110-6.

Shih D M, Gu L, Xia Y R, Navab M, Li W F, Hama S, Castellani L W, Furlong C E, Costa L G, Fogelman A M, Lusis A J Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature. 1998; 394(6690): 284-7.

Warden C H, Hedrick C C, Qiao J H, Castellani L W, Lusis A J Atherosclerosis in transgenic mice overexpressing apolipoprotein A-II. Science. 1993; 261(5120): 469-72.

Rajavashisth T B, Andalibi A, Territo M C, Berliner J A, Navab M, Fogelman A M, Lusis A J Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low-density lipoproteins. Nature. 1990; 344(6263): 254-7.

Lusis A J, West R, Mehrabian M, Reuben M A, LeBoeuf R C, Kaptein J S, Johnson D F, Schumaker V N, Yuhasz M P, Schotz M C Cloning and expression of apolipoprotein B, the major protein of low and very low density lipoproteins. Proceedings of the National Academy of Sciences of the United States of America. 1985; 82(14): 4597-601.