Career Interests
- CAR-T cell Therapy for Haematological Malignancies
- Genome editing of T-cells
- Virus Specific T-cells
- CAR-T and NK cell Therapy for blood disorders
- Engineering T-regulatory cells for therapeutic applications
- Genome editing of T/NK-cells
Education
- Post-Doctoral Research Fellow (2017-2023): St. Jude Children’s Research Hospital, Memphis, TN, USA.
- PhD in Biochemistry and Biomedical sciences (2012-2017): Department of Haematology, Christian Medical College, Vellore, India.
- M. Phil in Endocrinology (2007-2008): PGIBMS, University of Madras, Chennai, India.
- MSc in Biochemistry (2005-2007):Thiruvalluvar University, Vellore, India.
Awards
- PM ANRF ECRG-2026
- DBT-Ramalingaswami re-entry fellowship (2023).
- Abstract Achievement Award Recipient, American Society of Hematology Annual Meeting (2013, 2015 and 2020), USA.
- Young scientist travel award from Department of Science and Technology, India (2015).
- Young scientist travel award from Department of Biotechnology, India (2013).
- Indian council for Medical Research (ICMR) Senior Research Fellowship (2014-2017).
- Silver medal in M.Sc. (Thiruvalluvar University).
Our laboratory focuses on developing next-generation, gene-edited immune cell therapies for the treatment of haematological malignancies and autoimmune diseases. We integrate advanced genome-editing technologies, cellular engineering and adoptive cell therapy approaches to develop effective, safe and scalable off-the-shelf allogeneic cellular therapeutics.
A major research focus is the development of universal allogeneic Chimeric Antigen Receptor (CAR) T cells using CRISPR-based cytosine base-editing technology. We employ multiplex editing of TRAC and B2M to reduce T-cell receptor (TCR) and HLA class I expression, respectively, with the aim of minimizing graft-versus-host disease and host-mediated immune rejection. Our laboratory has successfully optimized multiplex base editing in primary human T cells and generated gene-edited CD19 CAR-T cells that retain CAR expression, expansion, phenotype and anti-tumour functionality. Their therapeutic potential is being evaluated through in vitro functional assays and preclinical in vivo models.
Building on this platform, we are developing next-generation dual- and bispecific CAR-T cells targeting CD19/CD20 for B-cell malignancies and CD19/BCMA for systemic lupus erythematosus (SLE). These approaches aim to improve target coverage and explore the therapeutic potential of engineered cellular therapies beyond cancer.
Our broader research interests include the development of induced pluripotent stem cell (iPSC)-derived CAR-NK cells targeting CD33/CD123 for acute myeloid leukaemia (AML) and the engineering and expansion of regulatory T cells (Tregs) for immune modulation in aplastic anaemia. By combining genome editing, stem cell technology and immune cell engineering, our long-term goal is to develop innovative, reproducible and scalable cellular immunotherapies with the potential for broader clinical translation.
- Phillip A Doerfler, Yichao Li, Yu Yao, Ruopeng Feng, Thiyagaraj Mayuranathan, Jingjing Zhang, Emilia Kooienga, David L Cullins, Rohith Jesudas, Dillon C Williams, Jane S Hankins, Yong Cheng, David K Wood, Mitchell J Weiss. Single-cell transcriptomics reveals heterocellular γ-globin gene expression in Aγδβ-thalassemia. Blood Advances. 2026 Feb 24;10(4):1163-1167. 10.1182/bloodadvances.2025016755. [PMID 41351474].
- Henry W Bell, Ruopeng Feng, Manan Shah, Yu Yao, James Douglas, Phillip A Doerfler, Thiyagaraj Mayuranathan, Michael F O'Dea, Yichao Li, Yong-Dong Wang, Jingjing Zhang, Joel P Mackay, Yong Cheng, Kate G R Quinlan, Mitchell J Weiss, Merlin Crossley. Removal of promoter CpG methylation by epigenome editing reverses HBG silencing. Nature Communications. 2025 Jul 27;16(1):6919. 10.1038/s41467-025-62177-z. [PMID 40715076].
- Yoonjeong Jang, Ruopeng Feng, Lance E Palmer, Thiyagaraj Mayuranathan, Yu Yao, Kalin Mayberry, Sheng Zhou, Jian Xu, Jeffrey Michael Gossett, Guolian Kang, Yong Cheng, Jonathan S Yen, Mitchell J Weiss. BCL11A-deficient human erythropoiesis is impaired in vitro and after xenotransplantation into mice. Blood Advances. 2025 Feb 28:2024015574. 10.1182/bloodadvances.2024015574. [PMID 40020162].
- Senthil Velan Bhoopalan, Thiyagaraj Mayuranathan, Nana Liu, Kalin Mayberry, Yu Yao, Jingjing Zhang, Jean-Yves Métais, Koon-Kiu Yan, Robert E. Throm, Steven R Ellis, Yan Ju, Lei Han1, Shruthi Suryaprakash, Lance E. Palmer, Sheng Zhou, Jiyang Yu, Yong Cheng, Jonathan S. Yen, Stephen Gottschalk, Mitchell J. Weiss. Preclinical development of lentiviral vector gene therapy for Diamond-Blackfan anemia syndrome. Molecular Therapy. 2024 Dec 12:S1525-0016(24)00819-0. doi: 10.1016/j.ymthe.2024.12.020. [PMID 39673126].
- Thiyagaraj Mayuranathan, Gregory A. Newby, Ruopeng Feng, Yu Yao, Kalin D. Mayberry, Cicera R. Lazzarotto, Yichao Li, Rachel M. Levine, Nikitha Nimmagadda, Erin A. D. Dempsey, Guolian Kang, Shaina N. Porter, Phillip A. Doerfler, Jingjing Zhang, Yoonjeong Jang, Jingjing Chen, Henry W. Bell, Merlin Crossley, Senthil Velan Bhoopalan, Akshay Sharma, John F. Tisdale, Shondra M. Pruett-Miller, Yong Cheng, Shengdar Q. Tsai, David R. Liu, Mitchell J. Weiss, Jonathan S. Yen. Potent and uniform fetal hemoglobin induction via base editing. Nature Genetics. 2023 Jul;55(7):1210-1220. doi: 10.1038/s41588-023-01434-7 [PMID 37400614].
- Christophe Lechauve, Julia Keith, Alfonso G Fernandez, Eugene Khandros, Kalin Mayberry, Thiyagaraj Mayuranathan, Lance E Palmer, Xiaohui Qiu, Heather Sheppard, Rahul Telange, Hans-Martin Herz, Mitchell J Weiss. Ancestral β-globin gene haplotypes modify β-thalassemia severity in a mouse model. Blood Advances. 2024 Mar 27:bloodadvances.2024012681. doi: 10.1182/bloodadvances. [PMID 38536944]
- Kelcee A. Everette , Gregory A. Newby, Rachel M. Levine, Kalin Mayberry, Yoonjeong Jang, Thiyagaraj Mayuranathan, Nikitha Nimmagadda, Erin Dempsey, Yichao Li, Senthil Velan Bhoopalan, Xiong Liu, Jessie R. Davis, Andrew T. Nelson, Peter J. Chen, Alexander A. Sousa1, Yong Cheng, John F. Tisdale, Mitchell J. Weiss , Jonathan S. Yen 4 & David R. Liu. Ex vivo prime editing of patient haematopoietic stem cells rescues sickle-cell disease phenotypes after engraftment in mice. Nature Biomedical Engineering. 2023 Apr 17. doi: 10.1038/s41551-023-01026-0. [PMID 37069266].
- Florence Borot, Olivier Humbert, Gregory A Newby, Emily Fields, Sajeev Kohli, Stefan Radtke, George S Laszlo, Thiyagaraj Mayuranathan, Abdullah Mahmood Ali, Mitchell J Weiss, Jonathan S Yen, Roland B Walter, David R Liu, Siddhartha Mukherjee, Hans-Peter Kiem. Multiplex Base Editing to Protect from CD33-Directed Therapy: Implications for Immune and Gene Therapy. bioRxiv. 2023 Feb 23;2023.02.23.529353. [PMID: 36865281].
- Ruopeng Feng, Thiyagaraj Mayuranathan, Peng Huang, Phillip A Doerfler, Yichao Li, Yu Yao, Jingjing Zhang, Lance E Palmer, Kalin Mayberry, Georgios E Christakopoulos, Peng Xu, Chunliang Li, Yong Cheng, Gerd A Blobel, M Celeste Simon, Mitchell J Weiss. Activation of γ-globin expression by hypoxia-inducible factor 1α. Nature. 2022 Oct;610(7933):783-790. [PMID: 36224385].
- Senthil Velan Bhoopalan, Jonathan S Yen, Thiyagaraj Mayuranathan, Kalin D Mayberry, Yu Yao, Maria Angeles Lillo Osuna, Yoonjeong Jang, Janaka Ss Liyange, Lionel Blanc, Steven R Ellis, Marcin W Wlodarski, Mitchell J Weiss. An RPS19-edited model for Diamond-Blackfan anemia reveals TP53-dependent impairment of hematopoietic stem cell activity. JCI insight. 2022 Nov 22;e161810. [PMID 36413407].
- Kunhua Qin , Peng Huang, Ruopeng Feng, Cheryl A Keller , Scott A Peslak, Eugene Khandros, Megan S Saari, Xianjiang Lan, Thiyagaraj Mayuranathan, Phillip A Doerfler, Osheiza Abdulmalik , Belinda Giardine, Stella T Chou , Junwei Shi, Ross C Hardison, Mitchell J Weiss , Gerd A Blobel. Dual function NFI factors control fetal hemoglobin silencing in adult erythroid cells. Nature Genetics. 2022
Jun;54(6):874-884. [PMID: 35618846]. - Gregory Newby*, Jonathan Yen*, Kaitly Woodard*, Thiyagaraj Mayuranathan*, Cicera Lazzarotto, Yichao Li, Heather Tillman, Shaina Porter, Yu Yao, Kalin Mayberry, Kelcee Everette, Elizabeth Thaman, Christope Lechauve, Akshay Sharma, Jordana Henderson, Michelle Richter, Kevin Zhao, Shannon Miller, Tina Wang, Luke Koblan, Anton McCaffrey, John Tisdale, Theodosia Kalfa, Shondra Pruett-Miller, Shengdar Tsai, Mitchell Weiss, David R Liu. Base editing rescues sickle cell disease in human hematopoietic stem cells and in mice. Nature. 2021 Jul;595 (7866):295-302. [PMID 34079130]. (* Equal Contribution).
- Xianjiang Lan, Ren Ren, Ruopeng Feng, Lana C Ly, Yemin Lan, Zhe Zhang, Nicholas Aboreden, Kunhua Qin, John R Horton, Jeremy D Grevet, Thiyagaraj Mayuranathan, Osheiza Abdulmalik, Cheryl A Keller, Belinda Giardine, Ross C Hardison, Merlin Crossley, Mitchell J Weiss, Xiaodong Cheng, Junwei Shi, Gerd A Blobel. ZNF410 Uniquely Activates the NuRD Component CHD4 to Silence Fetal Hemoglobin Expression. Molecular Cell. 2020 Dec 1; S1097-2765(20)30784-X. [PMID 33301730].
- Jean-Yves Metais*, Phillip A Doerfler*, Thiyagaraj Mayuranathan*, Daniel E Bauer, Stephanie C Fowler, Matthew M Hsieh, Varun Katta, Sagar Keriwala, Cicera R Lazzarotto, Kevin Luk, Michael D Neel, S Scott Perry, Samuel T Peters, Shaina N Porter, Byoung Y Ryu, Akshay Sharma, Devlin Shea, John F Tisdale, Naoya Uchida, Scot A Wolfe, Kaitly J Woodard, Yuxuan Wu, Yu Yao, Jing Zeng, Shondra Pruett-Miller, Shengdar Q Tsai, Mitchell J Weiss. Genome editing of HBG1 and HBG2 to induce fetal hemoglobin. Blood advances. 2019 Nov 12;3(21):3379-3392. [PMID 31698466]. (*Equal Contribution).
- Syed Mohammed Musheer Aalam, Kannan Vrindavan Manian, Sumitha Prameela Bharathan, Thiyagaraj Mayuranathan, Shaji Ramachandran Velayudhan. Identification of Stable OCT4+ NANOG− State in Somatic Cell Reprogramming. Cellular Reprogramming. 2016 Nov;18(6):367-368. [PMID 27622636].
- Thiyagaraj Mayuranathan, Janakiram Rayabaram, Reena Das, Neeraj Arora, Eunice S Edison, Mammen Chandy, Alok Srivastava, Shaji R Velayudhan. Identification of rare and novel deletions that cause (δβ) 0‐thalassaemia and hereditary persistence of foetal haemoglobin in Indian population. European Journal of Haematology. 2014 Jun;92(6):514-20. [24471888].
- Thiyagaraj Mayuranathan, Janakiram Rayabaram, Eunice Sindhuvi Edison, Alok Srivastava, Shaji R Velayudhan. A novel deletion of β-globin promoter causing high HbA2 in Indian population. Haematologica. 2012 Sep;97(9):1445-7. [PMID: 22581004].
- Sukyee Kwok, Susan R Rittling, Nicola C Partridge, Chellakkan S Benson, Mayuranathan Thiyagaraj, Narasimhan Srinivasan, Nagarajan Selvamurugan. Transforming growth factor‐beta1 regulation of ATF‐3 and identification of ATF‐3 target genes in breast cancer cells. Journal of Cellular Biochemistry. 2009 Oct 1;108(2):408- 14. [PMID: 19582787].
-
Systems and methods for base editing of HBG1/2 gene promoter and fetal hemoglobin induction. (SJ 20-0020, Status-pending).
- Dr Alok Srivastava CSCR/CMC
- Dr Mohankumar KM, CSCR
- Dr. Shaji RV, CSCR
- Dr. Uday Kulkarni, CMC
- Dr. Poonkuzhali, CMC
- Dr. Ruchika Goel, CMC
- Dr. Nihal Thomas, CSCR
- Dr. Mohankumar Murugesan, CSCR
- Dr. Biju George, CMC
- Dr. Diya Katrina, CMC