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Laboratory

Koren Mann's laboratory

The laboratory of Koren Mann was established in 2009 and is located within the Lady Davis Institute for Medical Research. The lab’s mission is to advance research in the field of metal exposure and toxicity. Our lab undertakes a multitude of in vivo and in vitro projects with a focus on heavy metals, exploring their properties, interactions, and consequences across various domains. By unraveling the mechanisms of how these metals interact with the body, we strive to enhance our understanding of their effects and contribute to the development of strategies for mitigating their potential harmful consequences.

One of the lab’s main outstanding features is its multidisciplinary approach, bringing experts together from various fields such as immunology, molecular biology, and bioinformatics. This collaborative effort allows for a comprehensive understanding of the complex nature of metals and will allow us to better understand their effects.

The lab has current and past research funding from the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, the Leukemia and Lymphoma Society of Canada, the Cancer Research Society, the Heart and Stroke Foundation of Canada and the US National Institutes of Health. Trainees have support from the Fonds de recherche du Québec-Santé, the Cole Foundation, the Canadian Institutes of Health Research, and McGill Internal Fellowships.

Meet the Team

Koren Mann 1

Research

Koren Mann 2

Tungsten is a heavy metal that accumulated in the bone and interferes with immature B cell development and differentiation. These tungsten-induced changes are correlated with altered DNA damage and repair mechanisms. There is very little information on tungsten toxicity; therefore, this project investigates whether tungsten immunotoxicity extends to mature B cell populations and to understand the mechanism behind tungsten toxicity. Current projects include the role of the SLC26A2as a tungsten importer and the GATOR1/KICSTOR complexes in mediating cell death.

Koren Mann 3

Titre

Contemporary research has uncovered a role for environmental copper in the development and progression of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Previous research implicated non-ceruloplasmin bound copper in the aggravation of neurodegenerative phenotypes. Our research explores the role of copper in ALS progression through monitoring of copper biomarkers and analyses of copper metabolism gene expression.

Koren Mann 4

Arsenic is an internationally recognized environmental contaminant affecting many parts of the world. A number of Canadians live in rural areas and are dependent on groundwater that contains unregulated amounts of arsenic. Arsenic exposure is linked to a myriad of adverse health effects, such as cancer and cardiovascular diseases, especially atherosclerosis. This project aims to investigate if sex and diet acts as a modulator of arsenic-induced immune cell heterogeneity within atherosclerotic plaque. We also aim to elucidate the consequences of co-exposures of other heavy metals such as cadmium and trying to determine the role of the arsenic-3-methyltransferase in arsenic metabolism and excretion.

Koren Mann 5

Within the past decade, there has been a rapid rise in e-cigarette use among today’s youth. E-cigarettes contain a myriad of harmful chemicals and heavy metals. Despite their popularity, little is known about their health effects. This project aims to investigate the pathological effects of commercially available e-cigarette products, including atherosclerosis, fibrosis, and inflammatory effects.

Koren Mann 6

Organophosphate esters (OPEs) are a class of toxic chemicals used as flame retardants and plasticizers in building materials and commercial goods. Some OPEs can harm the immune system; specifically, by disrupting the ability of macrophages to engulf and digest foreign particles and cells through phagocytosis. In the present study, we aim to test if a Canadian household dust based OPE mixture will decrease phagocytic uptake of apoptotic cells and bacterial pathogens.

Koren Mann 7

Diffuse large B-cell lymphoma is a cancer of the lymphatic system causing patients to develop abnormal B lymphocytes. Approximately 30% to 40% of patients will succumb to relapsed/refractory disease. Our project uses mouse modelling to study this form of lymphoma. In particular, we have found that mutations in the transcription factor stat6 are enriched at disease relapse. Our current focus is to elucidate how this relapse contributes to remodeling of the tumor microenvironment.

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Team

Koren Mann

Koren Mann

Lorem

After graduating with a BSc in Biology from Nebraska Wesleyan University, Koren Mann obtained a PhD in Pathology/Immunology from Boston University School of Medicine. Following that, she completed a Postdoctoral Fellowship in Oncology at McGill, where she investigated the use of arsenic as a potential chemotherapy in cancer treatment. Today, she is the Chair of the Department of Pharmacology and Therapeutics, an Associate Member of the Department of Medicine, and a Senior Investigator at the Lady Davis Institute for Medical Research.

Research Associates

Koren Mann 8

Cynthia Guilbert, MSc

Team Arsenic

Cynthia is the Mann lab manager. She offers support to the students with their projects, experiments and troubleshooting. She maintains a productive and positive lab environment. One of her projects involves the creation of arsenic 3 methyltransferase (As3MT) flox mice. These mice are an important tool in dissecting the role of tissue-specific As3MT in arsenic toxicity, as well as potentially identifying alternative As3MT functions.
Koren Mann 8

Mitra Rezaie, BSc

Team Copper

Mitra is a research associate in the Mann Lab. After finishing her BSc in Physiology at McGill, she began her career at the Lady Davis Institute for Medical Research. Her project explores the role of copper, a metal commonly found in drinking water, in the progression of amyotrophic lateral sclerosis.

PhD Students

Koren Mann 8

Braeden Giles

Team OPE

Braeden is a PhD candidate in the Department of Pharmacology. He completed an Honours Bachelor of Science at Queen’s University with a specialization in Drug Development and Human Toxicology. His project focuses on elucidating the consequences of organophosphate esters exposure on macrophage function.

Koren Mann 8

Nivetha Subramaniam

Team Arsenic

Nivetha is a PhD candidate in the Department of Experimental Medicine. She completed her BSc in Biochemistry at Concordia University. Her project focuses on how a co-exposure to metals, such as arsenic and cadmium, affects the progression of atherosclerosis.

Koren Mann 8

Madelyn Abraham

Team Lymphoma

Madelyn is a PhD student in the department of Experimental Medicine. She uses mouse modelling to study Diffuse Large B Cell Lymphoma. In particular, she has found that mutations in the transcription factor STAT6 are enriched at disease relapse, and I study how this contributes to remodeling of the tumour microenvironment.

Koren Mann 8

Rowa Bakadlag

Team Tungsten

Rowa is a PhD candidate in the department of Experimental Medicine. She completed her BSc in Microbiology and Immunology in Saudi Arabia, then completed two MScs in Genetics and Parasitology at McGill University. Her work investigates tungsten toxicity focusing on SLC2A2 as a transporter and the effects on mature B lymphocytes.

MSc Students

Koren Mann 8

Vincenza Caruana

Team Vaping

Vincenza is an MSc. Student in the Department of Pharmacology. She completed her BSc. in Pharmacology at McGill University. Her project aims to elucidate the role of e-cigarette use on the murine cardiopulmonary system. Specifically, she is focusing on metal deposition in the lungs, and the progression of atherosclerosis due to these exposures.

Koren Mann 8

Ayse Nazli Zengin

Team Arsenic

Nazli Zengin is an MSc. student in the Department of Pharmacology. She has a background in pharmacology and environment. Her work currently focuses on elucidating how sex and diet modulate arsenic toxicity and its immunological and cardiovascular consequences.

Koren Mann 8

Andrew Little

Team Arsenic

Andrew is an MSc. student in the Department of Pharmacology who graduated from the B.Sc. program in Biochemistry at McGill in 2021. He works on a proteomics project centred around Arsenic 3-Methyltransferase and the question about whether it serves an additional function.

Koren Mann 8

Raymond Tu

Team Tungsten

Raymond is an MSc. Student in the Department of Pharmacology who completed his BSc. in Environmental Health Sciences from the UNC Chapel Hill as a as a Morehead-Cain Scholar. He received the McCall MacBain Scholarship in 2021. His project studies the mechanism of tungsten on mTORC1, a major regulator of cell growth and proliferation.

Koren Mann 8

Nikola Kukolj

Team Arsenic

Nikola is an incoming MSc Student who completed his undergraduate degree in Microbiology and Immunology at McGill University. He is currently working on an NSERC summer project that assesses the functional characterization of macrophages exposed to arsenic using murine bone marrow-derived macrophages.

Undergraduate Students

Koren Mann 8

Roni Juran

Team Vaping

Roni is a second-year BSc student in Chemistry at McGill. As an undergraduate student, she works on various projects across the lab, but is currently focused elucidating the correlation between nonalcoholic fatty liver disease and vaping.

Publications

  • T Been, B Alakhtar, H Traboulsi, T Tsering, A Bartolomucci, N Heimbach, S Paoli, J Burnier, KK Mann, DH Eidelman, and CJ Baglole. Chronic low-level JUUL aerosol exposure causes pulmonary immunologic, transcriptomic, and proteomic changes. FASEB J 37(2):e22732, 2023.
  • K Makhani, C Chiavatti, LF Negro Silva, M Lemaire, AM Bolt, N De Jay, B Giles, AN Zengin, CL Kleinman, and KK Mann. Arsenic causes distinct gene expression changes in macrophages polarized in vitro with either interferon-γ or interleukin 4. Toxicol Sci 192(1): 83-96, 2023.
  • F Santinon, YK Young, SV Del Rincon, and KK Mann. Analyzing the Tumor-Immune Microenvironment by Flow Cytometry. Methods Mol Bio 2614:17-36, 2023.
  • BH Giles and KK Mann. Arsenic as an immunotoxicant. Toxicol Appl Pharmacol 454: 116247, 2022.
  • J Huang, K El-Kersh, KK Mann, KA James, L Cai. Overview of the cardiovascular effects of environmental metals: New Preclinical and clinical insights. Toxicol Appl Pharm 454:116247, 2022.
  • A Domingo-Relloso, K Makhani, … KK Mann, A Navas-Acien. Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease. Circ Res 131(2):e51-e69, 2022.
  • SY Mersaoui, C Guilbert, H Chou, C Douillet, DS Bohle, M Stýblo, S Richard, KK Mann. Arsenic 3 methyltransferase (AS3MT) automethylates on cysteine residues in vitro. Arch Toxicol. 96(5): 1371-1386, 2022.
  • T Been, H Traboulsi, S Paoli, B Alakhtar, KK Mann, DH Eidelman, CJ Baglole. Differential impact of JUUL flavors on pulmonary immune modulation and oxidative stress responses in male and female mice. Arch Toxicol. 96(6):1783-1798, 2022.
  • A Benoit, E Bou-Petit, H Chou, M Lu, C Guilbert, S Assouline, RD Morin, S Dmitrienko, R Estrada-Tejedor, NA Johnson, KK Mann. Mutated RAS-associating proteins and ERK activation in relapse/refractory Diffuse Large B cell lymphoma. Scientific Reports Jan 17;12(1):779, 2022.
  • SEJ Preston, A Emond, F Pettersson, D Dupéré-Richer, MJ Abraham, A Riva, M Kinal, RN Rys, NA Johnson, KK Mann, SV Del Rincón, JD Licht, WH Miller. Acquired Resistance to EZH2 Inhibitor GSK343 Promotes the Differentiation of Human DLBCL Cell Lines toward an ABC-Like Phenotype. Mol Cancer Ther. Apr 1;21(4):511-521, 2022.
  • J Saliba, B Coutaud, K Makhani, N Epstein Roth, J Jackson, JY Park, N Gagnon, P Costa, T Jeyakumar, M Bury, N Beauchemin, KK Mann, V Blank. Loss of NFE2L3 protects against inflammation-induced colorectal cancer through modulation of the tumor microenvironment. Oncogene. Mar;41(11):1563-1575, 2022.
  • CR VanderSchee, D Frier, D Kuter, KK Mann, BP Jackson, and DS Bohle. Quantification of local zinc and tungsten deposits in bone with LA-ICP-MS using novel hydroxyapatite-collagen calibration standards. J Anal At Spectrom 36(11):2431-2438, 2021.
  • N Ghaddar, S Wang, B Woodvine, J Krishnamoorthy, V van Hoef, C Darini, U Kazimierczak, N Ah-Son, H Popper, M Johnson, L Officer, A Teodósio, M Broggini, KK Mann, M Hatzoglou, I Topisirovic, O Larsson, J Le Quesne, AE Koromilas. The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer. Nat Commun. Jul 30;12(1):4651, 2021.
  • MS Dahabieh, F Huang, C Goncalves, RE Flores González, S Prabhu, A Bolt, E Di Pietro, E Khoury, J Heath, ZY Xu, J Rémy-Sarrazin, KK Mann, A Orthwein, FM Boisvert, N Braverman, WH Miller, SV Del Rincón. Silencing PEX26 as an unconventional mode to kill drug-resistant cancer cells and forestall drug resistance. Autophagy. Jun 21:1-19, 2021.
  • LF Negro Silva, K Makhani, M Lemaire, CA Lemarié, D Plourde, AM Bolt, C Chiavatti, DS Bohle, S Lehoux, MS Goldberg, KK Mann. Sex-specific effects of prenatal inorganic and methylated arsenic exposure on atherosclerotic plaque development and composition in adult apoe-/- mice. Environ Health Perspect. May;129(5):57008, 2021.
  • MP Grant, CR VanderSchee, H Chou, A Bolt, LM Epure, D Kuter, J Antoniou, S Bohle, KK Mann, F Mwale. Tungsten accumulates in the intervertebral disc and vertebrae stimulating disc degeneration and upregulating markers of inflammation and pain. Eur Cell Mater. May 17;41:517-530, 2021.
  • RN Rys, CM Wever, D Geoffrion, C Goncalves, A Ghassemian, E Brailovski, J Ryan, L Stoica, J Hébert, T Petrogiannis-Haliotis, S Dmitrienko, S Frenkiel, A Staiger, G Ott, C Steidl, DW Scott, P Sesques, S Del Rincon, KK Mann, A Letai, NA Johnson. Apoptotic Blocks in Primary Non-Hodgkin B Cell Lymphomas Identified by BH3 Profiling.
  • Cancers (Basel). Feb 28;13(5):1002, 2021.
  • F Ujueta, A Navas-Acien, KK Mann, R Prashad, GA Lamas. Low-Level Metal Contamination and Chelation in Cardiovascular Disease-A Ripe Area for Toxicology Research. Toxicol Sci. May 27;181(2):135-147, 2021.
  • H Chou, MP Grant, AM Bolt, C Guilbert, D Plourde, F Mwale, KK Mann. Tungsten increases osteoclast differentiation in murine bone. Tox Sci Jan 6;179(1):135-146, 2021.
  • CK Rushton, SE Arthur, M Alcaide , M Cheung, A Jiang, KM Coyle , KLS Cleary, N Thomas, LK Hilton, N Michaud, S Daigle, J Davidson, K Bushell, S Yu, RN Rys, M Jain, L Shepherd, MA Marra, J Kuruvilla, M Crump, K Mann, S Assouline, JM Connors, C Steidl, MS Cragg, DW Scott, NA Johnson, RD Morin. : Genetic and evolutionary patterns of treatment resistance in relapsed B-cell lymphoma. Blood Advances Jul 14;4(13): 2886-2898, 2020
  • T Ebrahimian, F Dierick, D Simon, M Heidari, A Orthwein, KK Mann, S Lehoux. FHL2 Is Essential for Spleen T Cell-Dependent B Cell Activation and Antibody Response. Immunohorizons May 20;4(5):259-273, 2020.
  • C Guilbert, H Chou, AM Bolt, TH Wu, VM Luo, A Orthwein, KK Mann. A functional assay to assess toxicity during B cell development in vitro. Current Protocols in Toxicology Mar;83(1):e91, 2020.
  • C Vanderschee, D Kuter, H Chou, BP Jackson, KK Mann, DS Bohle. Addressing K/L Edge Overlap in Elemental Analysis from Micro X-ray Fluorescence: Bioimaging of Tungsten and Zinc in Bone Tissue Using Synchrotron Radiation and Laser Ablation Inductively Coupled Plasma Mass Spectrometry. Analytical and Bioanalytical Chemistry Jan;412(2):259-265, 2020.

Collaborations

Wilson Miller, Lady Davis Institute for Medical Research, Montreal

Sonia del Rincon, Lady Davis Institute for Medical Research, Montreal

Carolyn Baglole, RI-MUHC, McGill University, Montreal

Jun Ding, RI-MUHC, McGill University, Montreal

Susan Gaskin, Department of Chemical Engineering, McGill University, Montreal

Bernard Robaire, Department of Pharmacology, McGill University, Montreal

Brandon Pearson, Columbia University, New York

John Wise, University of Louisville, Kentucky

News/Milestones

Dr. Wilson Miller, Lady Davis Institute, Montreal

Dr. Sonia del Rincon, Lady Davis Institute, Montreal

Dr. Carolyn Baglole, RI-MUHC, McGill University, Montreal

Dr. Jun Ding, RI-MUHC, McGill University, Montreal

Dr. Susan Gaskin, Dep’t of Chemical Engineering, McGill University, Montreal

Dr. Bernard Robaire, Dep’t of Pharmacology McGill University, Montreal

Dr. Brandon Pearson, Columbia University, New York

Dr. John Wise, University of Louisville, Kentucky

Lorem ipsum dolor sit amet consectetur adipisicing elit. Maxime mollitia, molestiae quas vel sint commodi repudiandae consequuntur voluptatum laborum numquam blanditiis harum quisquam eius sed odit fugiat iusto fuga praesentium optio, eaque rerum! Provident similique accusantium nemo autem. Veritatis obcaecati tenetur iure eius earum ut molestias architecto voluptate aliquam nihil, eveniet aliquid culpa officia aut! Impedit sit sunt quaerat, odit, tenetur error, harum nesciunt ipsum debitis quas aliquid. Reprehenderit, quia. Quo neque error repudiandae fuga? Ipsa laudantium molestias eos sapiente officiis modi at sunt excepturi expedita sint? Sed quibusdam recusandae alias error harum maxime adipisci amet laborum. Perspiciatis minima nesciunt dolorem! Officiis iure rerum voluptates a cumque velit quibusdam sed amet tempora. Sit laborum ab, eius fugit doloribus tenetur fugiat, temporibus enim commodi iusto libero magni deleniti quod quam consequuntur! 

  1. How iMALDI can improve clinical diagnostics. Popp, R., Basik, M., Spatz, A., Batist, G., Zahedi, R.P., Borchers, C.H., 2018. Analyst Clin. Chem. 64, 1271–1272. 143, 2197–2203.
  2. Immuno-MALDI-TOF-MS in the Clinic. Zahedi, R.P., Parker, C.E., Borchers, C.H., 2018.

Awards

Nivetha Subramaniam:

  • Dr. Morris Karmazyn Fellowship Award – 2022 and 2023
  • Poster award – Society of Toxicology, 2022 and 2023
  • Poster award – Conference on Metal Toxicity and Carcinogenesis 2022

Rowa Bakadlag:

  • Award – Society of Toxicology, 2023
  • Doctoral Training Scholarship – FRQS, 2022

Braeden Giles:

  • Centre for Research in Reproduction and Development Fellowship, 2023
  • 3 Minute Thesis – Pharmacology McGill, 2023

Andrew Little:

  • Master’s Training Scholarship – CIHR, 2022

Nikola Kukolj:

  • Undergraduate Student Research Awards – NSERC, 2023

Links

Titre

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Titre

Events

Dr. Wilson Miller, Lady Davis Institute, Montreal

Dr. Sonia del Rincon, Lady Davis Institute, Montreal

Dr. Carolyn Baglole, RI-MUHC, McGill University, Montreal

Dr. Jun Ding, RI-MUHC, McGill University, Montreal

Dr. Susan Gaskin, Dep’t of Chemical Engineering, McGill University, Montreal

Dr. Bernard Robaire, Dep’t of Pharmacology McGill University, Montreal

Dr. Brandon Pearson, Columbia University, New York

Dr. John Wise, University of Louisville, Kentucky

Lorem ipsum dolor sit amet consectetur adipisicing elit. Maxime mollitia, molestiae quas vel sint commodi repudiandae consequuntur voluptatum laborum numquam blanditiis harum quisquam eius sed odit fugiat iusto fuga praesentium optio, eaque rerum! Provident similique accusantium nemo autem. Veritatis obcaecati tenetur iure eius earum ut molestias architecto voluptate aliquam nihil, eveniet aliquid culpa officia aut! Impedit sit sunt quaerat, odit, tenetur error, harum nesciunt ipsum debitis quas aliquid. Reprehenderit, quia. Quo neque error repudiandae fuga? Ipsa laudantium molestias eos sapiente officiis modi at sunt excepturi expedita sint? Sed quibusdam recusandae alias error harum maxime adipisci amet laborum. Perspiciatis minima nesciunt dolorem! Officiis iure rerum voluptates a cumque velit quibusdam sed amet tempora. Sit laborum ab, eius fugit doloribus tenetur fugiat, temporibus enim commodi iusto libero magni deleniti quod quam consequuntur! 

  1. How iMALDI can improve clinical diagnostics. Popp, R., Basik, M., Spatz, A., Batist, G., Zahedi, R.P., Borchers, C.H., 2018. Analyst Clin. Chem. 64, 1271–1272. 143, 2197–2203.
  2. Immuno-MALDI-TOF-MS in the Clinic. Zahedi, R.P., Parker, C.E., Borchers, C.H., 2018.

Support

Dr. Wilson Miller, Lady Davis Institute, Montreal

Dr. Sonia del Rincon, Lady Davis Institute, Montreal

Dr. Carolyn Baglole, RI-MUHC, McGill University, Montreal

Dr. Jun Ding, RI-MUHC, McGill University, Montreal

Dr. Susan Gaskin, Dep’t of Chemical Engineering, McGill University, Montreal

Dr. Bernard Robaire, Dep’t of Pharmacology McGill University, Montreal

Dr. Brandon Pearson, Columbia University, New York

Dr. John Wise, University of Louisville, Kentucky

Contact

Lady Davis Institute for Medical Research, Jewish General Hospital

3755 Côte Ste-Catherine Road
Montreal, Quebec H3T 1E2

Location: F-202 and F-231

Email:

koren.mann@mcgill.ca

Reception:

(514) 340-8260

Office:

(514) 340-8222 ext. 22760

Lab:

(514) 340-8222 ext. 24257