Alexandre Orthwein, MSc, PhD

Research Program

Cell and Molecular Biology
Phone Number

470-815-6983
Email Address

alexandre.orthwein@emory.edu

Biography

Alexandre Orthwein, MSc, PhD, is an assistant professor in the Department of Radiation Oncology at Emory University School of Medicine. Prior to joining Emory, Dr. Orthwein was an assistant professor in the Gerald Bronfman Department of Oncology at McGill University and a Principal Investigator at the Segal Cancer Centre within the Lady Davis Institute for Medical Research at the Jewish General Hospital, where he held the Canada Research Chair in genome stability and hematological malignancies.

Dr. Orthwein is member of the Cell and Molecular Biology Research Program at Winship Cancer Institute.

Education

Dr. Orthwein obtained his MSC and PhD from the Department of Microbiology and Immunology at the University of Montreal. There, he developed a strong interest in B-cell biology and hematological malignancies by studying a critical mutagenic enzyme called Activation Induced Deaminase in the laboratory of Dr. Javier M. Di Noia at the IRCM in Montreal, Canada.

He subsequently joined the laboratory of Dr. Daniel Durocher at the Lunenfeld-Tanenbaum Research Institute in Toronto, Canada for his postdoctoral training. There, he investigated the interplay between the cell cycle and the signaling/repair of DNA double-strand breaks, the most cytotoxic DNA lesions. In 2014, he became the recipient of the Young Canadian Cell Biologist of the Year awarded by the Canadian Society for Molecular Biosciences.

Titles & Roles

Assistant Professor, Department of Radiation Oncology

Emory University School of Medicine

Research

As a cancer biologist and molecular immunologist, Dr. Orthwein is primarily interested in understanding:

how DNA repair pathways are regulated in different physiological contexts, including antibody diversification during B-cell development;
how their dysregulation can lead to different pathologies, such as cancer and immunodeficiency syndromes;
how these pathways influence the response to radio- and chemotherapies and the risk of relapse/resistance, particularly for hematological cancers.
His research team uses cutting-edge technologies including genome editing technologies, proteomics and single-cell transcriptomic approaches to tackle these complex and significant knowledge gaps.

Publications

Title/Journal	Authors	Publication Date
Combination radiation and αPD-L1 enhance tumor control by stimulating CD8+ PD-1+ TCF-1+ T cells in the tumor-draining lymph node. Nature communications	Y Shen, E Connolly, M Aiello, C Zhou, P Chappa, H Song, P Tippitak, T Clark, M Cardenas, N Prokhnevska, A Mariniello, I De Bruyker, MS Pagadala, VR Dhere, S Rafiq, AH Kesarwala, A Orthwein, SN Thomas, SL Zhang, MK Khan, JB Dixon, GB Lesinski, MC Lowe, H Kissick, DS Yu, CM Paulos, NC Schmitt, ZS Buchwald	04/14/2025
Editorial Expression of Concern: 53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark. Nature	A Fradet-Turcotte, MD Canny, C Escribano-Díaz, A Orthwein, CCY Leung, H Huang, MC Landry, J Kitevski-LeBlanc, SM Noordermeer, F Sicheri, D Durocher	02/01/2025
The Neurodevelopmental Protein POGZ Suppresses Metastasis in Triple-Negative Breast Cancer by Attenuating TGFβ Signaling. Cancer research	J Heath, C Mirabelli, MG Annis, V Sabourin, S Hebert, S Findlay, H Kim, M Witcher, CL Kleinman, PM Siegel, A Orthwein, J Ursini-Siegel	11/15/2024
The E3 ubiquitin ligase Herc1 modulates the response to nucleoside analogs in acute myeloid leukemia. Blood advances	M Jankovic, WWL Poon, C Gonzales-Losada, GG Vazquez, B Sharif-Askari, Y Ding, C Craplet-Desombre, A Ilie, J Shi, Y Wang, AK Jayavelu, A Orthwein, FÉ Mercier	10/22/2024
An E3 ubiquitin ligase localization screen uncovers DTX2 as a novel ADP-ribosylation-dependent regulator of DNA double-strand break repair. The Journal of biological chemistry	B Djerir, I Marois, JC Dubois, S Findlay, T Morin, I Senoussi, L Cappadocia, A Orthwein, A Maréchal	08/01/2024
Radiation and anti-PD-L1 synergize by stimulating a stem-like T cell population in the tumor-draining lymph node. Research square	Y Shen, E Connolly, M Aiello, C Zhou, P Chappa, H Song, P Tippitak, T Clark, M Cardenas, N Prokhnevska, A Mariniello, MS Pagadala, VR Dhere, S Rafiq, AH Kesarwala, A Orthwein, SN Thomas, MK Khan, J Brandon Dixon, GB Lesinski, MC Lowe, H Kissick, DS Yu, CM Paulos, NC Schmitt, ZS Buchwald	03/06/2024
The Deubiquitylase Otub1 Regulates the Chemotactic Response of Splenic B Cells by Modulating the Stability of the γ-Subunit Gng2. Molecular and cellular biology	VM Luo, C Shen, S Worme, A Bhagrath, E Simo-Cheyou, S Findlay, S Hébert, W Wai Lam Poon, Z Aryanpour, T Zhang, RP Zahedi, J Boulais, ZS Buchwald, CH Borchers, JF Côté, CL Kleinman, JN Mandl, A Orthwein	01/01/2024
FIRRM cooperates with FIGNL1 to promote RAD51 disassembly during DNA repair. Science advances	E Pinedo-Carpio, J Dessapt, A Beneyton, L Sacre, MA Bérubé, R Villot, EG Lavoie, Y Coulombe, A Blondeau, J Boulais, A Malina, VM Luo, AM Lazaratos, JF Côté, FA Mallette, A Guarné, JY Masson, A Fradet-Turcotte, A Orthwein	08/09/2023
The mitochondrial pyruvate carrier complex potentiates the efficacy of proteasome inhibitors in multiple myeloma. Blood advances	S Findlay, R Nair, RA Merrill, Z Kaiser, A Cajelot, Z Aryanpour, J Heath, C St-Louis, D Papadopoli, I Topisirovic, J St-Pierre, M Sebag, AH Kesarwala, L Hulea, EB Taylor, M Shanmugam, A Orthwein	07/25/2023
B cell-specific knockout of AID protects against atherosclerosis. Scientific reports	T Ebrahimian, F Dierick, V Ta, M Kotsiopriftis, J O'Connor Miranda, KK Mann, A Orthwein, S Lehoux	05/30/2023
EIF4A inhibition targets bioenergetic homeostasis in AML MOLM-14 cells in vitro and in vivo and synergizes with cytarabine and venetoclax. Journal of experimental & clinical cancer research : CR	K Fooks, G Galicia-Vazquez, V Gife, A Schcolnik-Cabrera, Z Nouhi, WWL Poon, V Luo, RN Rys, R Aloyz, A Orthwein, NA Johnson, L Hulea, FE Mercier	12/09/2022
Systematic proximal mapping of the classical RAD51 paralogs unravel functionally and clinically relevant interactors for genome stability. PLoS genetics	E Simo Cheyou, J Boni, J Boulais, E Pinedo-Carpio, A Malina, D Sherill-Rofe, VM Luo, C Goncalves, H Bagci, A Maters, R Cuella-Martin, Y Tabach, S Del Rincon, JF Côté, B Rivera, A Orthwein	11/01/2022
In vivo genome-wide CRISPR screening in murine acute myeloid leukemia uncovers microenvironmental dependencies. Blood advances	FE Mercier, J Shi, DB Sykes, T Oki, M Jankovic, CH Man, YS Kfoury, E Miller, S He, A Zhu, R Vasic, J Doench, A Orthwein, F Michor, DT Scadden	09/13/2022