Karthickeyan Chella Krishnan , PhD

Dr. Chella Krishnan received his PhD in Systems Genetics from the University of Cincinnati in 2015 under the expert mentorship of Dr. Malak Kotb. He then completed his postdoctoral training with Dr. Jake Lusis in the Department of Medicine/Cardiology at the University of California, Los Angeles in 2021. Dr. Chella Krishnan joined the Department of Pharmacology and Systems Physiology in February 2021 and is currently an Assistant Professor. Dr. Chella Krishnan’s major research focus is to understand how host genetic background and sex differences influence the mitochondrial (dys)function and increases the susceptibility to cardiovascular and metabolic diseases. For additional information, please visit: Klab website.

B.Tech.: Anna University 2010 (Industrial Biotechnology)

Ph.D.: University of Cincinnati 2015 (Systems Genetics)

Dr. Chella Krishnan's major research focus is to understand the role of sex differences and mitochondrial (dys)function in the pathophysiology of non-alcoholic fatty liver disease (NAFLD).

One of the major complications of obesity affecting the liver, in the absence of alcohol, is NAFLD. It is estimated that 20-30% of the population worldwide are affected by NAFLD and is more prevalent in men than women, with men exhibiting severe NAFLD symptoms. Work in the K Lab is focused on understanding how host genetic background and sex differences influence the mitochondrial (dys)function and increases the susceptibility to NAFLD, and other cardiometabolic diseases such as obesity and diabetes.
 
The approaches we use include

1. a population-based ‘systems genetics’ approach to integrate information on natural genetic variations (host genetics) with molecular phenotypes (such as gene expression, proteomics, etc.) and clinical phenotypes, with a targeted focus on sex differences and mitochondria, to identify candidate genes.
2. characterizing the candidate genes in genetically modified mouse models and/or eukaryotic cell lines.
3. characterize the mitochondrial functions using a Seahorse Bioanalyzer.
4. characterize the molecular functions using RNA-Sequencing and Single Cell Genomics.

2015 -2021 Postdoctoral Fellow, University of California, Los Angeles, CA

2021 - Assistant Professor, University of Cincinnati, OH

Grant: #R00DK120875 Investigators:Chella Krishnan, Karthickeyan 02-12-2021 -01-31-2024 National Inst of Diabetes and Digestive and Kidney Disease Investigating the sex-specific roles of PKLR and CHCHD6 in insulin resistance and NAFLD Role:PI $249,000.00 Awarded Level:Federal

Grant: #R01HL167670-01A1 Investigators:Chella Krishnan, Karthickeyan; Hui, David 01-01-2024 -11-30-2028 National Heart, Lung and Blood Institute Sex-Specific Roles of L-PK in Cholesterol Metabolism and Atherosclerosis Role:PI 572069.00 Awarded Level:Federal

Grant: #1R01HL167670-01A1 Investigators:Chella Krishnan, Karthickeyan; Hui, David 01-01-2024 -11-30-2028 National Heart, Lung and Blood Institute Sex-Specific Roles of L-PK in Cholesterol Metabolism and Atherosclerosis Role:PI 63562.00 Awarded Level:Federal

Peer Reviewed Publications

Chella Krishnan, Karthickeyan; Floyd, Raquel R; Sabir, Simon; Jayasekera, Dulshan W; Leon-Mimila, Paola V; Jones, Anthony E; Cortez, Angel A; Shravah, Varun; Péterfy, Miklós; Stiles, Linsey; Canizales-Quinteros, Samuel; Divakaruni, Ajit S; Huertas-Vazquez, Adriana; Lusis, Aldons J (2021. ) Liver Pyruvate Kinase Promotes NAFLD/NASH in Both Mice and Humans in a Sex-Specific Manner.Cellular and molecular gastroenterology and hepatology, , 11 (2 ) ,389-406 More Information

Norheim, Frode; Chella Krishnan, Karthickeyan; Bjellaas, Thomas; Vergnes, Laurent; Pan, Calvin; Parks, Brian W; Meng, Yonghong; Lang, Jennifer; Ward, James A; Reue, Karen; Mehrabian, Margarete; Gundersen, Thomas E; Péterfy, Miklós; Dalen, Knut T; Drevon, Christian A; Hui, Simon T; Lusis, Aldons J; Seldin, Marcus M (2021. ) Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis.Molecular systems biology, , 17 (1 ) ,e9684 More Information

Acín-Pérez, Rebeca; Iborra, Salvador; Martí-Mateos, Yolanda; Cook, Emma C L; Conde-Garrosa, Ruth; Petcherski, Anton; Muñoz, Mª Del Mar; Martínez de Mena, Raquel; Krishnan, Karthickeyan Chella; Jiménez, Concepción; Bolaños, Juan Pedro; Laakso, Markku; Lusis, Aldon J; Shirihai, Orian S; Sancho, David; Enríquez, José Antonio (2020. ) Fgr kinase is required for proinflammatory macrophage activation during diet-induced obesity.Nature metabolism, , 2 (9 ) ,974-988 More Information

Zhang, Guanglin; Byun, Hyae Ran; Ying, Zhe; Blencowe, Montgomery; Zhao, Yuqi; Hong, Jason; Shu, Le; Chella Krishnan, Karthick; Gomez-Pinilla, Fernando; Yang, Xia (2020. ) Differential metabolic and multi-tissue transcriptomic responses to fructose consumption among genetically diverse mice.Biochimica et biophysica acta. Molecular basis of disease, , 1866 (1 ) ,165569 More Information

Chella Krishnan, Karthickeyan; Sabir, Simon; Shum, Michaël; Meng, Yonghong; Acín-Pérez, Rebeca; Lang, Jennifer M; Floyd, Raquel R; Vergnes, Laurent; Seldin, Marcus M; Fuqua, Brie K; Jayasekera, Dulshan W; Nand, Sereena K; Anum, Diana C; Pan, Calvin; Stiles, Linsey; Péterfy, Miklós; Reue, Karen; Liesa, Marc; Lusis, Aldons J (2019. ) Sex-specific metabolic functions of adipose Lipocalin-2.Molecular metabolism, , 30 ,30-47 More Information

Norheim, Frode; Hasin-Brumshtein, Yehudit; Vergnes, Laurent; Chella Krishnan, Karthickeyan; Pan, Calvin; Seldin, Marcus M; Hui, Simon T; Mehrabian, Margarete; Zhou, Zhiqiang; Gupta, Sonul; Parks, Brian W; Walch, Axel; Reue, Karen; Hofmann, Susanna M; Arnold, Arthur P; Lusis, Aldons J (2019. ) Gene-by-Sex Interactions in Mitochondrial Functions and Cardio-Metabolic Traits.Cell metabolism, , 29 (4 ) ,932-949.e4 More Information

Hui, Simon T; Kurt, Zeyneb; Tuominen, Iina; Norheim, Frode; C Davis, Richard; Pan, Calvin; Dirks, Darwin L; Magyar, Clara E; French, Samuel W; Chella Krishnan, Karthickeyan; Sabir, Simon; Campos-Pérez, Francisco; Méndez-Sánchez, Nahum; Macías-Kauffer, Luis; León-Mimila, Paola; Canizales-Quinteros, Samuel; Yang, Xia; Beaven, Simon W; Huertas-Vazquez, Adriana; Lusis, Aldons J (2018. ) The Genetic Architecture of Diet-Induced Hepatic Fibrosis in Mice.Hepatology (Baltimore, Md.), , 68 (6 ) ,2182-2196 More Information

Chella Krishnan, Karthickeyan; Mehrabian, Margarete; Lusis, Aldons J (2018. ) Sex differences in metabolism and cardiometabolic disorders.Current opinion in lipidology, , 29 (5 ) ,404-410 More Information

Norheim, Frode; Bjellaas, Thomas; Hui, Simon T; Chella Krishnan, Karthickeyan; Lee, Jakleen; Gupta, Sonul; Pan, Calvin; Hasin-Brumshtein, Yehudit; Parks, Brian W; Li, Daniel Y; Bui, Hai H; Mosier, Marian; Wu, Yuping; Huertas-Vazquez, Adriana; Hazen, Stanley L; Gundersen, Thomas E; Mehrabian, Margarete; Tang, W H Wilson; Hevener, Andrea L; Drevon, Christian A; Lusis, Aldons J (2018. ) Genetic, dietary, and sex-specific regulation of hepatic ceramides and the relationship between hepatic ceramides and IR.Journal of lipid research, , 59 (7 ) ,1164-1174 More Information

Seldin, Marcus M; Koplev, Simon; Rajbhandari, Prashant; Vergnes, Laurent; Rosenberg, Gregory M; Meng, Yonghong; Pan, Calvin; Phuong, Thuy M N; Gharakhanian, Raffi; Che, Nam; Mäkinen, Selina; Shih, Diana M; Civelek, Mete; Parks, Brian W; Kim, Eric D; Norheim, Frode; Chella Krishnan, Karthickeyan; Hasin-Brumshtein, Yehudit; Mehrabian, Margarete; Laakso, Markku; Drevon, Christian A; Koistinen, Heikki A; Tontonoz, Peter; Reue, Karen; Cantor, Rita M; Björkegren, Johan L M; Lusis, Aldons J (2018. ) A Strategy for Discovery of Endocrine Interactions with Application to Whole-Body Metabolism.Cell metabolism, , 27 (5 ) ,1138-1155.e6 More Information

Chella Krishnan, Karthickeyan; Kurt, Zeyneb; Barrere-Cain, Rio; Sabir, Simon; Das, Aditi; Floyd, Raquel; Vergnes, Laurent; Zhao, Yuqi; Che, Nam; Charugundla, Sarada; Qi, Hannah; Zhou, Zhiqiang; Meng, Yonghong; Pan, Calvin; Seldin, Marcus M; Norheim, Frode; Hui, Simon; Reue, Karen; Lusis, Aldons J; Yang, Xia (2018. ) Integration of Multi-omics Data from Mouse Diversity Panel Highlights Mitochondrial Dysfunction in Non-alcoholic Fatty Liver Disease.Cell systems, , 6 (1 ) ,103-115.e7 More Information

Seldin, Marcus M; Kim, Eric D; Romay, Milagros C; Li, Shen; Rau, Christoph D; Wang, Jessica J; Krishnan, Karthickeyan Chella; Wang, Yibin; Deb, Arjun; Lusis, Aldons J (2017. ) A systems genetics approach identifies Trp53inp2 as a link between cardiomyocyte glucose utilization and hypertrophic response.American journal of physiology. Heart and circulatory physiology, , 312 (4 ) ,H728-H741 More Information

Mairpady Shambat, Srikanth; Siemens, Nikolai; Monk, Ian R; Mohan, Disha B; Mukundan, Santhosh; Krishnan, Karthickeyan Chella; Prabhakara, Sushma; Snäll, Johanna; Kearns, Angela; Vandenesch, Francois; Svensson, Mattias; Kotb, Malak; Gopal, Balasubramanian; Arakere, Gayathri; Norrby-Teglund, Anna (2016. ) A point mutation in AgrC determines cytotoxic or colonizing properties associated with phenotypic variants of ST22 MRSA strains.Scientific reports, , 6 ,31360 More Information

Chella Krishnan, Karthickeyan; Mukundan, Santhosh; Alagarsamy, Jeyashree; Hur, Junguk; Nookala, Suba; Siemens, Nikolai; Svensson, Mattias; Hyldegaard, Ole; Norrby-Teglund, Anna; Kotb, Malak (2016. ) Genetic Architecture of Group A Streptococcal Necrotizing Soft Tissue Infections in the Mouse.PLoS pathogens, , 12 (7 ) ,e1005732 More Information

Chella Krishnan, Karthickeyan; Mukundan, Santhosh; Alagarsamy, Jeyashree; Laturnus, Donna; Kotb, Malak (2016. ) Host Genetic Variations and Sex Differences Potentiate Predisposition, Severity, and Outcomes of Group A Streptococcus-Mediated Necrotizing Soft Tissue Infections.Infection and immunity, , 84 (2 ) ,416-24 More Information

Chella Krishnan, Karthickeyan; Mukundan, Santhosh; Landero Figueroa, Julio A; Caruso, Joseph A; Kotb, Malak (2014. ) Metal-mediated modulation of streptococcal cysteine protease activity and its biological implications.Infection and immunity, , 82 (7 ) ,2992-3001 More Information

Ferrara, Patrick J; Rong, Xin; Maschek, J Alan; Verkerke, Anthony Rp; Siripoksup, Piyarat; Song, Haowei; Green, Thomas D; Krishnan, Karthickeyan C; Johnson, Jordan M; Turk, John; Houmard, Joseph A; Lusis, Aldons J; Drummond, Micah J; McClung, Joseph M; Cox, James E; Shaikh, Saame Raza; Tontonoz, Peter; Holland, William L; Funai, Katsuhiko (2021. ) Lysophospholipid acylation modulates plasma membrane lipid organization and insulin sensitivity in skeletal muscle.The Journal of clinical investigation, , 131 (8 ) , More Information

Acín-Perez, Rebeca; Petcherski, Anton; Veliova, Michaela; Benador, Ilan Y; Assali, Essam A; Colleluori, Georgia; Cinti, Saverio; Brownstein, Alexandra J; Baghdasarian, Siyouneh; Livhits, Masha J; Yeh, Michael W; Krishnan, Karthickeyan Chella; Vergnes, Laurent; Winn, Nathan C; Padilla, Jaume; Liesa, Marc; Sacks, Harold S; Shirihai, Orian S (2021. ) Recruitment and remodeling of peridroplet mitochondria in human adipose tissue.Redox biology, , 46 ,102087 More Information

Shum, Michael; Shintre, Chitra A; Althoff, Thorsten; Gutierrez, Vincent; Segawa, Mayuko; Saxberg, Alexandra D; Martinez, Melissa; Adamson, Roslin; Young, Margaret R; Faust, Belinda; Gharakhanian, Raffi; Su, Shi; Chella Krishnan, Karthickeyan; Mahdaviani, Kiana; Veliova, Michaela; Wolf, Dane M; Ngo, Jennifer; Nocito, Laura; Stiles, Linsey; Abramson, Jeff; Lusis, Aldons J; Hevener, Andrea L; Zoghbi, Maria E; Carpenter, Elisabeth P; Liesa, Marc (2021. ) ABCB10 exports mitochondrial biliverdin, driving metabolic maladaptation in obesity.Science translational medicine, , 13 (594 ) , More Information

Chella Krishnan, Karthickeyan (2023. ) When diet meets genetics.eLife, , 12 , More Information

Patel, Sanil; Sparman, Njeri Z R; Arneson, Douglas; Alvarsson, Alexandra; Santos, Luís C; Duesman, Samuel J; Centonze, Alessia; Hathaway, Ephraim; Ahn, In Sook; Diamante, Graciel; Cely, Ingrid; Cho, Chung Hwan; Talari, Noble Kumar; Rajbhandari, Abha K; Goedeke, Leigh; Wang, Peng; Butte, Atul J; Blanpain, Cédric; Chella Krishnan, Karthickeyan; Lusis, Aldons J; Stanley, Sarah A; Yang, Xia; Rajbhandari, Prashant (2023. ) Mammary duct luminal epithelium controls adipocyte thermogenic programme.Nature, , 620 (7972 ) ,192-199 More Information

Chella Krishnan, Karthickeyan; El Hachem, Elie-Julien; Keller, Mark P; Patel, Sanjeet G; Carroll, Luke; Vegas, Alexis Diaz; Gerdes Gyuricza, Isabela; Light, Christine; Cao, Yang; Pan, Calvin; Kaczor-Urbanowicz, Karolina Elżbieta; Shravah, Varun; Anum, Diana; Pellegrini, Matteo; Lee, Chi Fung; Seldin, Marcus M; Rosenthal, Nadia A; Churchill, Gary A; Attie, Alan D; Parker, Benjamin; James, David E; Lusis, Aldons J (2023. ) Genetic architecture of heart mitochondrial proteome influencing cardiac hypertrophy.eLife, , 12 , More Information

Cao, Yang; Vergnes, Laurent; Wang, Yu-Chen; Pan, Calvin; Chella Krishnan, Karthickeyan; Moore, Timothy M; Rosa-Garrido, Manuel; Kimball, Todd H; Zhou, Zhiqiang; Charugundla, Sarada; Rau, Christoph D; Seldin, Marcus M; Wang, Jessica; Wang, Yibin; Vondriska, Thomas M; Reue, Karen; Lusis, Aldons J (2022. ) Sex differences in heart mitochondria regulate diastolic dysfunction.Nature communications, , 13 (1 ) ,3850 More Information

Chella Krishnan, Karthickeyan; Vergnes, Laurent; Acín-Pérez, Rebeca; Stiles, Linsey; Shum, Michael; Ma, Lijiang; Mouisel, Etienne; Pan, Calvin; Moore, Timothy M; Péterfy, Miklós; Romanoski, Casey E; Reue, Karen; Björkegren, Johan L M; Laakso, Markku; Liesa, Marc; Lusis, Aldons J (2021. ) Sex-specific genetic regulation of adipose mitochondria and metabolic syndrome by Ndufv2.Nature metabolism, , 3 (11 ) ,1552-1568 More Information

Book Chapter

Nookala, Suba; Chella Krishnan, Karthickeyan; Mukundan, Santhosh; Kotb, Malak (2020 ) Systems Genetics Approaches in Mouse Models of Group A Streptococcal Necrotizing Soft-Tissue Infections Necrotizing Soft Tissue Infections .(pp. 151-166).Springer, Cham (Co-Author)

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