Lev Becker | Metabolism

Research Summary

Macrophage dysregulation is a hallmark of chronic sterile inflammatory diseases including cancer, atherosclerosis, and obesity/type 2 diabetes. Because macrophages are highly influenced by their environment, we need to understand how disease-specific changes to their environment dysregulate specific pathways to drive pathogenesis. Moreover, the relationship between these macrophage pathways to those required for pathogen clearance is largely unknown, which is important because attempts to therapeutically target macrophages must preserve this important function. Comparing and contrasting macrophages across a spectrum of diseases is therefore required to elucidate disease-specific mechanisms, and to develop therapeutics that are both efficacious and safe. To enable this, my lab combines proteomic, bioinformatic, immunologic, and functional approaches to study macrophages in an unbiased manner across a spectrum of diseases. Our long-term goal is to develop a robust research program that uses a multi-disease approach to develop a comprehensive understanding of macrophage biology, and then translates this mechanistic understanding to develop therapeutics across a spectrum of human disease. To this end, my lab is developing 2 new therapies for the treatment of many cancers and anti-inflammatory therapies that do not interfere with pathogen clearance for treating atherosclerosis and type 2 diabetes.

Keywords

Macrophages, Cancer, Type 2 Diabetes Mellitus, Atherosclerosis, Proteomics, Bioinformatics, Translational Research, Therapeutics, Immunology, Innate Immunity

Education

Queen's University, Kingston, ON, CAN, PhD Biochemistry 09/2003
University of Washington, Seattle, WA, USA, Post-doctoral studies Proteomics, Macrophages 09/2009

Biosciences Graduate Program Association

Awards & Honors

2002 - 2003 Doctoral Research Fellowship Heart and Stroke Foundation of Canada
2005 - 2008 Postdoctoral Research Fellowship Canadian Institutes of Health and Research
2008 - 2008 Young Investigator Award 3rd International Symposium Integrated Biomarkers in Cardiovascular Disease
2014 - 2016 Young Investigator Award Cancer Research Foundation
2017 - 2020 J Clifford Moos Award for Cancer Research University of Chicago

Publications

Cui C, Chakraborty K, Tang XA, Schoenfelt KQ, Hoffman A, Blank A, McBeth B, Pulliam N, Reardon CA, Kulkarni SA, Vaisar T, Ballabio A, Krishnan Y, Becker L. A lysosome-targeted DNA nanodevice selectively targets macrophages to attenuate tumours. Nat Nanotechnol. 2021 Nov 11. View in: PubMed
Suresh B, Saminathan A, Chakraborty K, Zajac M, Cui C, Becker L, Krishnan Y. Tubular lysosomes harbor active ion gradients and poise macrophages for phagocytosis. Proc Natl Acad Sci U S A. 2021 Oct 12; 118(41). View in: PubMed
Cui C, Schoenfelt KQ, Becker KM, Becker L. Isolation of polymorphonuclear neutrophils and monocytes from a single sample of human peripheral blood. STAR Protoc. 2021 Dec 17; 2(4):100845. View in: PubMed
Webster KL, Becker L. Surplus Ceramides: An Added Twist in the Tale of TREM2 and Insulin Resistance. Diabetes. 2021 09; 70(9):1926-1928. View in: PubMed
Cui C, Chakraborty K, Tang XA, Zhou G, Schoenfelt KQ, Becker KM, Hoffman A, Chang YF, Blank A, Reardon CA, Kenny HA, Vaisar T, Lengyel E, Greene G, Becker L. Neutrophil elastase selectively kills cancer cells and attenuates tumorigenesis. Cell. 2021 Jun 10; 184(12):3163-3177.e21. View in: PubMed
Gebhardt MJ, Czyz DM, Singh S, Zurawski DV, Becker L, Shuman HA. GigC, a LysR Family Transcription Regulator, Is Required for Cysteine Metabolism and Virulence in Acinetobacter baumannii. Infect Immun. 2020 12 15; 89(1). View in: PubMed
Hisert KB, Birkland TP, Schoenfelt KQ, Long ME, Grogan B, Carter S, Liles WC, McKone EF, Becker L, Manicone AM, Gharib SA. CFTR Modulator Therapy Enhances Peripheral Blood Monocyte Contributions to Immune Responses in People With Cystic Fibrosis. Front Pharmacol. 2020; 11:1219. View in: PubMed
Kahn JH, Goddi A, Sharma A, Heiman J, Carmona A, Li Y, Hoffman A, Schoenfelt K, Ye H, Bobe AM, Becker L, Hollenberg AN, Cohen RN. SMRT Regulates Metabolic Homeostasis and Adipose Tissue Macrophage Phenotypes in Tandem. Endocrinology. 2020 10 01; 161(10). View in: PubMed
Hisert KB, Birkland TP, Schoenfelt KQ, Long ME, Grogan B, Carter S, Liles WC, McKone EF, Becker L, Manicone AM. Ivacaftor decreases monocyte sensitivity to interferon-? in people with cystic fibrosis. ERJ Open Res. 2020 Apr; 6(2). View in: PubMed
Dick BP, McMahan R, Knowles T, Becker L, Gharib SA, Vaisar T, Wietecha T, O'Brien KD, Bornfeldt KE, Chait A, Kim F. Hematopoietic Cell-Expressed Endothelial Nitric Oxide Protects the Liver From Insulin Resistance. Arterioscler Thromb Vasc Biol. 2020 03; 40(3):670-681. View in: PubMed
Zhang D, Tang Z, Huang H, Zhou G, Cui C, Weng Y, Liu W, Kim S, Lee S, Perez-Neut M, Ding J, Czyz D, Hu R, Ye Z, He M, Zheng YG, Shuman HA, Dai L, Ren B, Roeder RG, Becker L, Zhao Y. Metabolic regulation of gene expression by histone lactylation. Nature. 2019 10; 574(7779):575-580. View in: PubMed
Tiwari P, Blank A, Cui C, Schoenfelt KQ, Zhou G, Xu Y, Khramtsova G, Olopade F, Shah AM, Khan SA, Rosner MR, Becker L. Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer. J Exp Med. 2019 06 03; 216(6):1345-1358. View in: PubMed
Thekkan S, Jani MS, Cui C, Dan K, Zhou G, Becker L, Krishnan Y. A DNA-based fluorescent reporter maps HOCl production in the maturing phagosome. Nat Chem Biol. 2019 12; 15(12):1165-1172. View in: PubMed
Goss CH, Kaneko Y, Khuu L, Anderson GD, Ravishankar S, Aitken ML, Lechtzin N, Zhou G, Czyz DM, McLean K, Olakanmi O, Shuman HA, Teresi M, Wilhelm E, Caldwell E, Salipante SJ, Hornick DB, Siehnel RJ, Becker L, Britigan BE, Singh PK. Gallium disrupts bacterial iron metabolism and has therapeutic effects in mice and humans with lung infections. Sci Transl Med. 2018 09 26; 10(460). View in: PubMed
Reardon CA, Lingaraju A, Schoenfelt KQ, Zhou G, Cui C, Jacobs-El H, Babenko I, Hoofnagle A, Czyz D, Shuman H, Vaisar T, Becker L. Obesity and Insulin Resistance Promote Atherosclerosis through an IFN?-Regulated Macrophage Protein Network. Cell Rep. 2018 06 05; 23(10):3021-3030. View in: PubMed
Singhal H, Greene ME, Zarnke AL, Laine M, Al Abosy R, Chang YF, Dembo AG, Schoenfelt K, Vadhi R, Qiu X, Rao P, Santhamma B, Nair HB, Nickisch KJ, Long HW, Becker L, Brown M, Greene GL. Progesterone receptor isoforms, agonists and antagonists differentially reprogram estrogen signaling. Oncotarget. 2018 Jan 12; 9(4):4282-4300. View in: PubMed
Coats BR, Schoenfelt KQ, Barbosa-Lorenzi VC, Peris E, Cui C, Hoffman A, Zhou G, Fernandez S, Zhai L, Hall BA, Haka AS, Shah AM, Reardon CA, Brady MJ, Rhodes CJ, Maxfield FR, Becker L. Metabolically Activated Adipose Tissue Macrophages Perform Detrimental and Beneficial Functions during Diet-Induced Obesity. Cell Rep. 2017 Sep 26; 20(13):3149-3161. View in: PubMed
Frankenberger C, Rabe D, Bainer R, Sankarasharma D, Chada K, Krausz T, Gilad Y, Becker L, Rosner MR. Metastasis Suppressors Regulate the Tumor Microenvironment by Blocking Recruitment of Prometastatic Tumor-Associated Macrophages. Cancer Res. 2015 Oct 01; 75(19):4063-73. View in: PubMed
Kratz M, Coats BR, Hisert KB, Hagman D, Mutskov V, Peris E, Schoenfelt KQ, Kuzma JN, Larson I, Billing PS, Landerholm RW, Crouthamel M, Gozal D, Hwang S, Singh PK, Becker L. Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Cell Metab. 2014 Oct 07; 20(4):614-25. View in: PubMed
Almendros I, Wang Y, Becker L, Lennon FE, Zheng J, Coats BR, Schoenfelt KS, Carreras A, Hakim F, Zhang SX, Farré R, Gozal D. Intermittent hypoxia-induced changes in tumor-associated macrophages and tumor malignancy in a mouse model of sleep apnea. Am J Respir Crit Care Med. 2014 Mar 01; 189(5):593-601. View in: PubMed
Yurkovetskiy L, Burrows M, Khan AA, Graham L, Volchkov P, Becker L, Antonopoulos D, Umesaki Y, Chervonsky AV. Gender bias in autoimmunity is influenced by microbiota. Immunity. 2013 Aug 22; 39(2):400-12. View in: PubMed