Dr. Shaji R Velayudhan

Career Interests

Awards

• MSc: Marine Biotechnology Goa University (1991-1993).
• PhD: Christian Medical College, Vellore (1995-2001).
• Post Doctoral Research Fellowship:  St Jude Children's Research Hospital, Memphis (2004-2006).
• Post Doctoral Research Fellowship: University of Chicago, Chicago.

Disease Modelling Using Induced Pluripotent Stem Cells (iPSCs):

Our laboratory is involved in disease modeling using iPSCs for understanding the molecular basis of disease pathogenesis and for drug screening on the differentiated cells derived from disease-specific iPSCs. Recently, we generated iPSC lines from the fibroblasts of a patient with Fanconi anemia (FA) by nonintegrative methods, after complementing the defective gene with a normal gene using a doxycycline-inducible lentiviral vector. The iPSCs generated were completely characterized for their pluripotency and, in the absence of doxycycline, these cells showed the cellular phenotypes of FA including cell cycle arrest, lack of FANCD2 monoubiquitination and absence of co-localization of FANCD2 and gamma H2AX. Currently, we are using these iPSC lines to understand the molecular basis of Fanconi Anaemia disease pathogenesis. In addition to FA, using a similar approach, we are creating disease models for Congenital Dyserythropoietic Anaemia (CDA) and Diamond Blackfan Anaemia (DBA).

Fig 1: Establishment of IndC-FANCA-iPSC line that exhibits the FA cellular phenotypes. (A) Schematic of molecular diagnosis of FANCA deficiency and iPSC generation. (B) Morphology of iPSCs grown on feeder layers (upper figure) and feeder-free vitronectin coated plates (lower figure). (C) Immunofluorescence analysis of NANOG, OCT4, SOX2, SSEA-4, TRA-1-81 and TRA-1-60. (D) Real-time PCR analysis of mRNA levels of NANOG, OCT4, SOX2, GDF3 AND DNMT3B, relative to the BC1 control iPSC line (data represented as mean±SD). (E) H&E-staining of teratoma sections showing trilineage differentiation; hc-hyaline cartilage (mesoderm), ne-neuroepithelium (ectoderm) and ce-columnar epithelium (endoderm). (F) Chromosome analysis showing normal male karyotype. (G) Western blot analysis of the cells treated with Hydroxyurea showing the lack of FANCD2-monoubiquitination in the absence of DOX and FANCA expression. L and S indicate the larger monoubiquitinated and the smaller unmodified FANCD2 bands, respectively. (H) Immunofluorescence analysis showing nuclear foci formed by ?H2A.X and FANCD2. The nuclei are stained with DAPI (violet colour). In DOX+ cells, colocalization of the foci formed by ?H2A.X and FANCD2 are seen as yellow spots due to the merging of green spots of ?H2A.X foci and red spots of FANCD2 foci, and in DOX- cells, only green spots of ?H2A.X foci are seen. (I) EdU incorporation based cell cycle analysis showing a spontaneous progressive G2/M arrest in the absence of DOX and FANCA expression for two passages. (J) Alkaline phosphatase staining showing spontaneous progressive exhaustion of iPSCs in the absence of DOX and FANCA expression for two passages.

Induced pluripotent stem cells:

Introduction of four transcription factors Oct-4, Sox2, Klf4 and c-Myc into adult cells can covert them to pluripotent stem cells. These induced pluripotent stem cells (iPSCs) exhibit features characteristic of embryonic stem (ES) cells. These cells have exciting new prospects for biomedical research, drug discovery and for regenerative medicine. Our lab is interested in understanding the mechanism of the reprogramming process and the use of these cells to understand the pathophysiology of human diseases.

A. miPSCs exhibited mouse embryonic stem cell like morphology and high level of expression of alkaline phosphatase (AP). Expression of other pluripotency markers SSEA-1, Oct4 and Nanog were examined by immunofluorescence.

B. miPSCs formed embryoid bodies and could be differentiated into lineages from all three germ layers. Immunostaining for (i) alpha-fetoprotein (AFP; endoderm), smooth muscle actin (SMA; mesoderm) and b3 tubulin (ectoderm) are shown.

Mechanism of globin gene regulation

During human development, three different types of hemoglobins are produced; embryonic, fetal and adult hemoglobins. In this project we are trying to understand the roles of transcription factors and epigenetics in developmental stage specific regulation of globin genes. We are also trying to understand the regulatory sequences in the globin clusters that help in stage specific expression of these genes. We are carrying out ex-vivo differentiation of haematopoietic stem cells to erythroid lineage and studying interaction of proteins with the DNA sequences using chromatin immunoprecipitation followed by microarray (ChIP-chip) to understand the roles of transcription factors and epigenetic changes in the regulation of globin genes.

Selected Publications

• Prasad K, Devaraju N, George A, Ravi NS, Paul J, Mahalingam G, Rajendiran V, Panigrahi L, Venkatesan V, Lakhotiya K, Periyasami Y, Pai AA, Nakamura Y, Kurita R, Balasubramanian P, Thangavel S, Velayudhan SR, Newby GA, Marepally S, Srivastava A, Mohankumar KM. Precise correction of a spectrum of β-thalassemia mutations in coding and non-coding regions by base editors. Mol Ther Nucleic Acids. 2024 May 3;35(2):102205. doi: 10.1016/j.omtn.2024.102205. PMID: 38817682; PMCID: PMC11137594.
• Jebanesan DZP, Illangeswaran RSS, Rajamani BM, Vidhyadharan RT, Das S, Bijukumar NK, Balakrishnan B, Mathews V, Velayudhan SR, Balasubramanian P. Inhibition of NRF2 signaling overcomes acquired resistance to arsenic trioxide in FLT3-mutated Acute Myeloid Leukemia. Ann Hematol. 2024 Jun;103(6):1919-1929. doi: 10.1007/s00277-024-05742-8. Epub 2024 Apr 17. PMID: 38630133.
• Ijee S, Chambayil K, Chaudhury AD, Bagchi A, Modak K, Das S, Benjamin ESB, Rani S, Paul DZ, Nath A, Roy D, Palani D, Priyanka S, Ravichandran R, Kumary BK, Sivamani Y, S V, Babu D, Nakamura Y, Thamodaran V, Balasubramanian P, Velayudhan SR. Efficient deletion of microRNAs using CRISPR/Cas9 with dual guide RNAs. Front Mol Biosci. 2024 Apr 2;10:1295507. doi: 10.3389/fmolb.2023.1295507. PMID:38628442; PMCID: PMC11020096.
• Benjamin ESB, Vinod E, Illangeswaran RSS, Rajamani BM, Vidhyadharan RT,Bagchi A, Maity A, Mohan A, Parasuraman G, Amirtham SM, Abraham A, Velayudhan SR, Balasubramanian P. Immortalised chronic myeloid leukemia (CML) derived mesenchymal stromal cells (MSCs) line retains the immunomodulatory and chemoprotective properties of CML patient-derived MSCs. Cell Signal. 2024. Apr;116:111067. doi: 10.1016/j.cellsig.2024.111067. Epub 2024 Jan 27. PMID: 38281615.
• Rajendiran V, Devaraju N, Haddad M, Ravi NS, Panigrahi L, Paul J, Gopalakrishnan C, Wyman S, Ariudainambi K, Mahalingam G, Periyasami Y, Prasad K, George A, Sukumaran D, Gopinathan S, Pai AA, Nakamura Y, Balasubramanian P, Ramalingam R, Thangavel S, Velayudhan SR, Corn JE, Mackay JP, Marepally S, Srivastava A, Crossley M, Mohankumar KM. Base editing of key residues in the BCL11A-XL-specific zinc finger domains derepresses fetal globin expression. Mol Ther. 2024 Mar 6;32(3):663-677. doi: 10.1016/j.ymthe.2024.01.023. Epub 2024 Jan 24. PMID: 38273654; PMCID: PMC10928131.
• Nandy K, Babu D, Rani S, Joshi G, Ijee S, George A, Palani D, Premkumar C, Rajesh P, Vijayanand S, David E, Murugesan M, Velayudhan SR. Efficient gene editing in induced pluripotent stem cells enabled by an inducible adenine base editor with tunable expression. Sci Rep. 2023 Dec 11;13(1):21953. doi: 10.1038/s41598-023-42174-2. PMID: 38081875; PMCID: PMC10713686.
• Rani S, Thamodaran V, Nandy K, Fouzia NA, Maddali M, Rajesh P, Vijayanand S, David E, Velayudhan SR. Establishment and characterization of CSCRi006-A: an induced pluripotent stem cell line generated from a patient with Diamond-Blackfan Anemia (DBA) carrying ribosomal protein S19 (RPS19) mutation. Hum Cell. 2023 Nov;36(6):2204-2213. doi: 10.1007/s13577-023-00946-y. Epub 2023 Aug 21. PMID: 37603219.
• Raina K, Joshi G, Modak K, Premkumar C, Priyanka S, Rajesh P, Velayudhan SR, Thummer RP. Generation and characterization of induced pluripotent stem cell line IITGi001-A derived from adult human primary dermal fibroblasts. Stem Cell Res. 2023 Sep;71:103159. doi: 10.1016/j.scr.2023.103159. Epub 2023 Jun 28. PMID: 37392703.
• Rajamani BM, Illangeswaran RSS, Benjamin ESB, Balakrishnan B, Jebanesan DZP, Das S, Pai AA, Vidhyadharan RT, Mohan A, Karathedath S, Abraham A, Mathews V, Velayudhan SR, Balasubramanian P. Modulating retinoid-X-receptor alpha (RXRA) expression sensitizes chronic myeloid leukemia cells to imatinib <i>in vitro</i>and reduces disease burden <i>in vivo</i>. Front Pharmacol. 2023 May 31;14:1187066. doi: 10.3389/fphar.2023.1187066. PMID: 37324449; PMCID: PMC10264673.
• Illangeswaran RSS, Jebanesan DZP, Sivakumar KK, Vidhyadharan RT, Rajamani BM, Janet NB, David E, Velayudhan SR, Mathews V, Balasubramanian P. Corrigendum to "Chemotherapeutic drugs elicit stemness and metabolic alteration to mediate acquired drug-resistant phenotype in acute myeloid leukemia cell lines" [Leukemia Res. 128, 107054]. Leuk Res. 2023 Jul;130:107329. doi: 10.1016/j.leukres.2023.107329. Epub 2023 May 29. Erratum for: Leuk Res. 2023 May;128:107054. doi: 10.1016/j.leukres.2023.107054. PMID: 37258357.
• Venkatesan V, Christopher AC, Rhiel M, Azhagiri MKK, Babu P, Walavalkar K, Saravanan B, Andrieux G, Rangaraj S, Srinivasan S, Karuppusamy KV, Jacob A, Bagchi A, Pai AA, Nakamura Y, Kurita R, Balasubramanian P, Pai R, Marepally SK, Mohankumar KM, Velayudhan SR, Boerries M, Notani D, Cathomen T, Srivastava A, Thangavel S. Editing the core region in HPFH deletions alters fetal and adult globin expression for treatment of β-hemoglobinopathies. Mol Ther Nucleic Acids. 2023 Apr 26;32:671-688. doi: 10.1016/j.omtn.2023.04.024. PMID: 37215154; PMCID: PMC10197010.
• Illangeswaran RSS, Jebanesan DZP, Sivakumar KK, Vidhyadharan RT, Rajamani BM, Janet NB, David E, Velayudhan SR, Mathews V, Balasubramanian P. Chemotherapeutic drugs elicit stemness and metabolic alteration to mediate acquired drug-resistant phenotype in acute myeloid leukemia cell lines. Leuk Res. 2023 May;128:107054. doi: 10.1016/j.leukres.2023.107054. Epub 2023 Mar 3. Erratum in: Leuk Res. 2023 Jul;130:107329. doi: 10.1016/j.leukres.2023.107329. PMID: 36906941.
• Joshi G, Arthur NBJ, Geetha TS, Datari PVR, Modak K, Roy D, Chaudhury AD, Sundaraganesan P, Priyanka S, Na F, Ramprasad V, Abraham A, Srivastava VM, Srivastava A, Kulkarni UP, George B, Velayudhan SR. Comprehensive laboratory diagnosis of Fanconi anaemia: comparison of cellular and molecular analysis. J Med Genet. 2023 Aug;60(8):801-809. doi: 10.1136/jmg-2022-108714. Epub 2023 Mar 9. PMID: 36894310; PMCID: PMC10423531.
• George A, Ravi NS, Prasad K, Panigrahi L, Koikkara S, Rajendiran V, Devaraju N, Paul J, Pai AA, Nakamura Y, Kurita R, Balasubramanian P, Thangavel S, Marepally S, Velayudhan SR, Srivastava A, Mohankumar KM. Efficient and error-free correction of sickle mutation in human erythroid cells using prime editor-2. Front Genome Ed. 2022 Dec 20;4:1085111. doi: 10.3389/fgeed.2022.1085111. PMID: 36605051; PMCID: PMC9808041.
• Dahariya S, Raghuwanshi S, Thamodaran V, Velayudhan SR, Gutti RK. Role of Long Non-Coding RNAs in Human-Induced Pluripotent Stem Cells Derived Megakaryocytes: A p53, HOX Antisense Intergenic RNA Myeloid 1, and miR-125b Interaction Study. J Pharmacol Exp Ther. 2023 Jan;384(1):92-101. doi: 10.1124/jpet.121.001095. Epub 2022 Oct 15. PMID: 36243404.
• Bagchi A, Devaraju N, Chambayil K, Rajendiran V, Venkatesan V, Sayed N, Pai AA, Nath A, David E, Nakamura Y, Balasubramanian P, Srivastava A, Thangavel S, Mohankumar KM, Velayudhan SR. Erythroid lineage-specific lentiviral RNAi vectors suitable for molecular functional studies and therapeutic applications. Sci Rep. 2022 Aug 18;12(1):14033. doi: 10.1038/s41598-022-13783-0. PMID: 35982069; PMCID: PMC9388678.
• Das S, Stallon Illangeswaran RS, Ijee S, Kumar S, Velayudhan SR, Balasubramanian P. Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype. J Vis Exp. 2022 Jun 17;(184):10.3791/63383. doi: 10.3791/63383. PMID: 35786700; PMCID: PMC7614927.
• Mahalingam G, Rachamalla HK, Arjunan P, Periyasami Y, M S, Thangavel S, Mohankumar KM, Moorthy M, Velayudhan SR, Srivastava A, Marepally S. Optimization of SARS-CoV-2 Pseudovirion Production in Lentivirus Backbone With a Novel Liposomal System. Front Pharmacol. 2022 Mar 25;13:840727. doi: 10.3389/fphar.2022.840727. PMID: 35401169; PMCID: PMC8990231.
• Ravi NS, Wienert B, Wyman SK, Bell HW, George A, Mahalingam G, Vu JT, Prasad K, Bandlamudi BP, Devaraju N, Rajendiran V, Syedbasha N, Pai AA, Nakamura Y, Kurita R, Narayanasamy M, Balasubramanian P, Thangavel S, Marepally S, Velayudhan SR, Srivastava A, DeWitt MA, Crossley M, Corn JE, Mohankumar KM. Identification of novel HPFH-like mutations by CRISPR base editing that elevate the expression of fetal hemoglobin. Elife. 2022 Feb 11;11:e65421. doi: 10.7554/eLife.65421. PMID: 35147495; PMCID: PMC8865852.
• Nath A, Rayabaram J, Ijee S, Bagchi A, Chaudhury AD, Roy D, Chambayil K, Singh J, Nakamura Y, Velayudhan SR. Comprehensive Analysis of microRNAs in Human Adult Erythropoiesis. Cells. 2021 Nov 4;10(11):3018. doi: 10.3390/cells10113018. PMID: 34831239; PMCID: PMC8616439.
• Christopher AC, Venkatesan V, Karuppusamy KV, Srinivasan S, Babu P, Azhagiri MKK, Chambayil K, Bagchi A, Rajendiran V, Ravi NS, Kumar S, Marepally SK, Mohankumar KM, Srivastava A, Velayudhan SR, Thangavel S. Preferential Expansion of Human CD34⁺CD133⁺CD90⁺ Hematopoietic Stem Cells Enhances Gene-Modified Cell Frequency for Gene Therapy. Hum Gene Ther. 2022 Feb;33(3-4):188-201. doi: 10.1089/hum.2021.089. Epub 2022 Jan 7. PMID: 34486377.
• Singh G, Manian KV, Premkumar C, Srivastava A, Daniel D, Velayudhan SR. Derivation of Clinical-Grade Induced Pluripotent Stem Cell Lines from Erythroid Progenitor Cells in Xenofree Conditions. Methods Mol Biol. 2022;2454:775-789. doi: 10.1007/7651_2021_349. PMID: 33950379.
• Thamodaran V, Rani S, Velayudhan SR. Gene Editing in Human Induced Pluripotent Stem Cells Using Doxycycline-Inducible CRISPR-Cas9 System. Methods Mol Biol. 2022;2454:755-773. doi: 10.1007/7651_2021_348. PMID: 33830454; PMCID: PMC7612904.
• Bagchi A, Nath A, Thamodaran V, Ijee S, Palani D, Rajendiran V, Venkatesan V, Datari P, Pai AA, Janet NB, Balasubramanian P, Nakamura Y, Srivastava A, Mohankumar KM, Thangavel S, Velayudhan SR. Direct Generation of Immortalized Erythroid Progenitor Cell Lines from Peripheral Blood Mononuclear Cells. Cells. 2021 Mar 1;10(3):523. doi: 10.3390/cells10030523. PMID: 33804564; PMCID: PMC7999632.
• Ravindra N, Athiyarath R, S E, S S, Kulkarni U, N A F, Korula A, Shaji RV, George B, Edison ES. Novel frameshift variant (c.409dupG) in <i>SLC25A38</i> is a common cause of congenital sideroblastic anaemia in the Indian subcontinent. J Clin Pathol. 2021 Mar;74(3):157-162. doi: 10.1136/jclinpath-2020-206647. Epub 2020 Jun 30. PMID: 32605921.
• Benjamin ESB, Ravindra N, Rajamani BM, Anandan S, Kausalya B, Veldore V, Mathews V, Velayudhan SR, Balasubramanian P. <i>BCR-ABL1</i> kinase domain mutation analysis by next generation sequencing detected additional mutations in chronic myeloid leukemia patients with suboptimal response to imatinib. Leuk Lymphoma. 2021 Jun;62(6):1528-1531. doi: 10.1080/10428194.2021.1872074. Epub 2021 Jan 22. PMID: 33478278; PMCID: PMC7611165.
• Arunachalam AK, Suresh H, Edison ES, Korula A, Aboobacker FN, George B, Shaji RV, Mathews V, Balasubramanian P. Screening of genetic variants in <i>ELANE</i>mutation negative congenital neutropenia by next generation sequencing. J Clin Pathol. 2020 Jun;73(6):322-327. doi: 10.1136/jclinpath-2019-206306. Epub 2019 Nov 15. PMID: 31732620.
• Sullivan S, Stacey GN, Akazawa C, Aoyama N, Baptista R, Bedford P, Bennaceur Griscelli A, Chandra A, Elwood N, Girard M, Kawamata S, Hanatani T, Latsis T, Lin S, Ludwig TE, Malygina T, Mack A, Mountford JC, Noggle S, Pereira LV, Price J, Sheldon M, Srivastava A, Stachelscheid H, Velayudhan SR, Ward NJ, Turner ML, Barry J, Song J. Quality control guidelines for clinical-grade human induced pluripotent stem cell lines. Regen Med. 2018 Oct;13(7):859-866. doi: 10.2217/rme-2018-0095. Epub 2018 Sep 12. PMID: 30205750.
• Manian KV, Bharathan SP, Maddali M, Srivastava VM, Srivastava A, Velayudhan SR. Generation of an integration-free iPSC line (CSCRi005-A) from erythroid progenitor cells of a healthy Indian male individual. Stem Cell Res. 2018 May;29:148-151. doi: 10.1016/j.scr.2018.03.020. Epub 2018 Apr 3. PMID: 29665501.
• Dharmalingam P, Marrapu B, Voshavar C, Nadella R, Rangasami VK, Shaji RV, Abbas S, Prasad RBN, Kaki SS, Marepally S. An anti-oxidant, α-lipoic acid conjugated oleoyl-sn-phosphatidylcholineas a helper lipid in cationic liposomal formulations. Colloids Surf B Biointerfaces. 2017 Apr 1;152:133-142. doi: 10.1016/j.colsurfb.2017.01.013. Epub 2017 Jan 10. PMID: 28103530.
• Fouzia NA, Edison ES, Lakshmi KM, Korula A, Velayudhan SR, Balasubramanian P, Abraham A, Viswabandya A, George B, Mathews V, Srivastava A. Long-term outcome of mixed chimerism after stem cell transplantation for thalassemia major conditioned with busulfan and cyclophosphamide. Bone Marrow Transplant. 2018 Feb;53(2):169-174. doi: 10.1038/bmt.2017.231. Epub 2017 Oct 16. PMID: 29035392.
• Karathedath S, Rajamani BM, Musheer Aalam SM, Abraham A, Varatharajan S, Krishnamurthy P, Mathews V, Velayudhan SR, Balasubramanian P. Role of NF-E2 related factor 2 (Nrf2) on chemotherapy resistance in acute myeloid leukemia (AML) and the effect of pharmacological inhibition of Nrf2. PLoS One. 2017 May 15;12(5):e0177227. doi: 10.1371/journal.pone.0177227. PMID: 28505160; PMCID: PMC5432104.
• Bharathan SP, Nandy K, Palani D, Janet A NB, Natarajan K, George B, Srivastava A, Velayudhan SR. Generation of an induced pluripotent stem cell line that mimics the disease phenotypes from a patient with Fanconi anemia by conditional complementation. Stem Cell Res. 2017 Apr;20:54-57. doi: 10.1016/j.scr.2017.02.006. Epub 2017 Feb 22. PMID: 28395741.
• Srivastava A, Shaji RV. Cure for thalassemia major - from allogeneic hematopoietic stem cell transplantation to gene therapy. Haematologica. 2017 Feb;102(2):214-223. doi: 10.3324/haematol.2015.141200. Epub 2016 Dec 1. PMID: 27909215; PMCID: PMC5286930.
• Bharathan SP, Manian KV, Aalam SM, Palani D, Deshpande PA, Pratheesh MD, Srivastava A, Velayudhan SR. Systematic evaluation of markers used for the identification of human induced pluripotent stem cells. Biol Open. 2017 Jan 15;6(1):100-108. doi: 10.1242/bio.022111. PMID: 28089995; PMCID: PMC5278432.
• Aalam SM, Manian KV, Bharathan SP, Mayuranathan T, Velayudhan SR. Identification of Stable OCT4⁺NANOG^- State in Somatic Cell Reprogramming. Cell Reprogram. 2016 Nov;18(6):367-368. doi: 10.1089/cell.2016.0018. Epub 2016 Sep 13. PMID: 27622636.
• Jayasree D, Shaji RV, George B, Mathews V, Srivastava A, Edison ES. Clinical, Hematological and Molecular Analysis of Homozygous Hb E (HBB: c.79G > A) in the Indian Population. Hemoglobin. 2016;40(1):16-9. doi: 10.3109/03630269.2015.1086880. Epub 2015 Nov 11. PMID: 26554862.
• Kamath MS, Pradhan S, Edison ES, Velayudhan SR, Antonisamy B, Karthikeyan M, Mangalaraj AM, Kunjummen A, George K. Chorionic villous sampling through transvaginal ultrasound approach: A retrospective analysis of 1138 cases. J Obstet Gynaecol Res. 2016 Oct;42(10):1229-1235. doi: 10.1111/jog.13070. Epub 2016 Jun 29. PMID: 27352773.
• Pal R, Mariappan I, Velayudhan SR. Editorial: Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells: Ushering of a New Era in Personalized Cell Therapies. Curr Stem Cell Res Ther. 2016;11(2):97-8. doi: 10.2174/1574888x1102160107174225. PMID: 26592539.
• Deshpande P, Kathirvel K, Alex AA, Korula A, George B, Shaji RV, Mathews V. Leukocyte Adhesion Deficiency-I: Clinical and Molecular Characterization in an Indian Population. Indian J Pediatr. 2016 Aug;83(8):799-804. doi: 10.1007/s12098-016-2051-0. Epub 2016 Feb 29. PMID: 26924654.
• Deshpande P, Kamalanathan N, Sampath E, George B, Shaji RV, Edison ES. Characterization of Clinical and Laboratory Profiles of the Deletional α2-Globin Gene Polyadenylation Signal Sequence (AATAAA > AATA- -) in an Indian Population. Hemoglobin. 2015;39(6):415-8. doi: 10.3109/03630269.2015.1079785. Epub 2015 Sep 12. PMID: 26365411.
• Manian KV, Aalam SM, Bharathan SP, Srivastava A, Velayudhan SR. Understanding the Molecular Basis of Heterogeneity in Induced Pluripotent Stem Cells. Cell Reprogram. 2015 Dec;17(6):427-40. doi: 10.1089/cell.2015.0013. Epub 2015 Nov 12. PMID: 26562626.
• Abraham A, Varatharajan S, Karathedath S, Philip C, Lakshmi KM, Jayavelu AK, Mohanan E, Janet NB, Srivastava VM, Shaji RV, Zhang W, Abraham A, Viswabandya A, George B, Chandy M, Srivastava A, Mathews V, Balasubramanian P. RNA expression of genes involved in cytarabine metabolism and transport predicts cytarabine response in acute myeloid leukemia. Pharmacogenomics. 2015 Jul;16(8):877-90. doi: 10.2217/pgs.15.44. Epub 2015 Jun 17. PMID: 26083014; PMCID: PMC7115907.
• Mayuranathan T, Rayabaram J, Das R, Arora N, Edison ES, Chandy M, Srivastava A, Velayudhan SR. Identification of rare and novel deletions that cause (δβ)0-thalassaemia and hereditary persistence of foetal haemoglobin in Indian population. Eur J Haematol. 2014 Jun;92(6):514-20. doi: 10.1111/ejh.12276. Epub 2014 Mar 15. PMID: 24471888.
• Edison ES, Sathya M, Rajkumar SV, Nair SC, Srivastava A, Shaji RV. A novel β-globin gene mutation HBB.c.22 G>C produces a hemoglobin variant (Hb Vellore) mimicking HbS in HPLC. Int J Lab Hematol. 2012 Oct;34(5):556-8. doi: 10.1111/j.1751-553X.2012.01418.x. Epub 2012 Apr 4. PMID: 22471768.
• Edison ES, Venkatesan RS, Govindanattar SD, George B, Shaji RV. A novel 26 bp deletion [HBB: c.20_45del26bp] in exon 1 of the β-globin gene causing β-thalassemia major. Hemoglobin. 2012;36(1):98-102. doi: 10.3109/03630269.2011.641135. PMID: 22233277.
• Jain S, Edison ES, Mathews V, Shaji RV. A novel δ-globin gene mutation (HBD: c.323G>A) masking the diagnosis of β-thalassemia: a first report from India. Int J Hematol. 2012 May;95(5):570-2. doi: 10.1007/s12185-012-1032-y. Epub 2012 Apr 4. PMID: 22477537.
• David S, Jayandharan GR, Abraham A, Jacob RR, Devi GS, Patkar N, Shaji RV, Nair SC, Viswabandya A, Ahmed R, George B, Mathews V, Chandy M, Srivastava A. Molecular basis of Wiskott-Aldrich syndrome in patients from India. Eur J Haematol. 2012 Oct;89(4):356-60. doi: 10.1111/j.1600-0609.2012.01818.x. Epub 2012 Jul 14. PMID: 22679904.
• Abraham A, Varatharajan S, Abbas S, Zhang W, Shaji RV, Ahmed R, Abraham A, George B, Srivastava A, Chandy M, Mathews V, Balasubramanian P. Cytidine deaminase genetic variants influence RNA expression and cytarabine cytotoxicity in acute myeloid leukemia. Pharmacogenomics. 2012 Feb;13(3):269-82. doi: 10.2217/pgs.11.149. PMID: 22304580.
• Varatharajan S, Abraham A, Zhang W, Shaji RV, Ahmed R, Abraham A, George B, Srivastava A, Chandy M, Mathews V, Balasubramanian P. Carbonyl reductase 1 expression influences daunorubicin metabolism in acute myeloid leukemia. Eur J Clin Pharmacol. 2012 Dec;68(12):1577-86. doi: 10.1007/s00228-012-1291-9. Epub 2012 May 5. PMID: 22562609.
• Mayuranathan T, Rayabaram J, Edison ES, Srivastava A, Velayudhan SR. A novel deletion of β-globin promoter causing high HbA2 in an Indian population. Haematologica. 2012 Sep;97(9):1445-7. doi: 10.3324/haematol.2012.062299. Epub 2012 May 11. PMID: 22581004; PMCID: PMC3436249.
• Edison ES, Shaji RV, Chandy M, Srivastava A. Interaction of hemoglobin E with other abnormal hemoglobins. Acta Haematol. 2011;126(4):246-8. doi: 10.1159/000329904. Epub 2011 Oct 4. PMID: 21986214.
• Mathews V, George B, Chendamarai E, Lakshmi KM, Desire S, Balasubramanian P, Viswabandya A, Thirugnanam R, Abraham A, Shaji RV, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol. 2010 Aug 20;28(24):3866-71. doi: 10.1200/JCO.2010.28.5031. Epub 2010 Jul 19. PMID: 20644086.
• Markose P, Chendamarai E, Balasubramanian P, Velayudhan SR, Srivastava VM, Mathews V, George B, Viswabandya A, Srivastava A, Chandy M. Spectrum of BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia from India with suspected resistance to imatinib-mutations are rare and have different distributions. Leuk Lymphoma. 2009 Dec;50(12):2092-5. doi: 10.3109/10428190903332486. PMID: 19925053.
• Jayandharan GR, Nair SC, Poonnoose PM, Thomas R, John J, Keshav SK, Cherian RS, Devadarishini M, Lakshmi KM, Shaji RV, Viswabandya A, George B, Mathews V, Chandy M, Srivastava A. Polymorphism in factor VII gene modifies phenotype of severe haemophilia. Haemophilia. 2009 Nov;15(6):1228-36. doi:10.1111/j.1365-2516.2009.02080.x. Epub 2009 Aug 16. PMID: 19686262.
• Vivekanandan P, Daniel HD, Raghuraman S, Daniel D, Shaji RV, Sridharan G, Chandy G, Abraham P. Novel digestion patterns with hepatitis B virus strains from the Indian subcontinent detected using restriction fragment length polymorphism. Indian J Med Microbiol. 2008 Jan-Mar;26(1):96-7. doi: 10.4103/0255-0857.38878. PMID: 18227618.
• Santhosh S, Shaji RV, Eapen CE, Jayanthi V, Malathi S, Finny P, Thomas N, Chandy M, Kurian G, Chandy GM. Genotype phenotype correlation in Wilson's disease within families--a report on four south Indian families. World J Gastroenterol. 2008 Aug 7;14(29):4672-6. doi: 10.3748/wjg.14.4672. PMID: 18698682; PMCID: PMC2738792.
• Edison ES, Shaji RV, Devi SG, Moses A, Viswabandhya A, Mathews V, George B, Srivastava A, Chandy M. Analysis of beta globin mutations in the Indian population: presence of rare and novel mutations and region-wise heterogeneity. Clin Genet. 2008 Apr;73(4):331-7. doi: 10.1111/j.1399-0004.2008.00973.x. Epub 2008 Feb 20. PMID: 18294253.
• Sundaresan S, Eapen CE, Shaji RV, Chandy M, Kurian G, Chandy G. Screening for mutations in ATP7B gene using conformation-sensitive gel electrophoresis in a family with Wilson's disease. Med Sci Monit. 2007 Mar;13(3):CS38-40. PMID: 17325640.
• Sellathamby S, Balasubramanian P, Sivalingam S, Shaji RV, Mathews V, George B, Viswabandya A, Srivastava A, Chandy M. Developing an algorithm of informative markers for evaluation of chimerism after allogeneic bone marrow transplantation. Bone Marrow Transplant. 2006 Apr;37(8):751-5. doi:10.1038/sj.bmt.1705317. PMID: 16518431.
• Santhosh S, Shaji RV, Eapen CE, Jayanthi V, Malathi S, Chandy M, Stanley M, Selvi S, Kurian G, Chandy GM. ATP7B mutations in families in a predominantly Southern Indian cohort of Wilson's disease patients. Indian J Gastroenterol. 2006 Nov-Dec;25(6):277-82. PMID: 17264425.
• Das R, Garewal G, Shaji RV, Ahluwalia J, Bali HK, Varma S. Investigation of persistent hypochromic microcytosis unmasks hemoglobin Evanston [alpha 14 (A12) Try--> Arg] in a patient of cyclic thrombocytopenia preceding Takayasu's disease. Hematology. 2005 Oct;10(5):427-9. doi: 10.1080/10245330500214148. PMID: 16273737.
• George B, Mathews V, Shaji RV, Srivastava V, Srivastava A, Chandy M. Fludarabine-based conditioning for allogeneic stem cell transplantation for multiply transfused patients with Fanconi's anemia. Bone Marrow Transplant. 2005 Feb;35(4):341-3. doi: 10.1038/sj.bmt.1704785. PMID: 15640819.
• Jayandharan GR, Shaji RV, Baidya S, Nair SC, Chandy M, Srivastava A. Molecular characterization of factor IX gene mutations in 53 patients with haemophilia B in India. Thromb Haemost. 2005 Oct;94(4):883-6. PMID: 16270648.
• Jayandharan G, Shaji RV, Baidya S, Nair SC, Chandy M, Srivastava A. Identification of factor VIII gene mutations in 101 patients with haemophilia A: mutation analysis by inversion screening and multiplex PCR and CSGE and molecular modelling of 10 novel missense substitutions. Haemophilia. 2005 Sep;11(5):481-91. doi: 10.1111/j.1365-2516.2005.01121.x. PMID: 16128892.
• Jayandharan G, Viswabandya A, Baidya S, Nair SC, Shaji RV, George B, Chandy M, Srivastava A. Six novel mutations including triple heterozygosity for Phe31Ser, 514delT and 516T-->G factor X gene mutations are responsible for congenital factor X deficiency in patients of Nepali and Indian origin. J Thromb Haemost. 2005 Jul;3(7):1482-7. doi: 10.1111/j.1538-7836.2005.01339.x. Epub 2005 May 9. PMID: 15892863.
• Jayandharan G, Viswabandya A, Baidya S, Nair SC, Shaji RV, Chandy M, Srivastava A. Molecular genetics of hereditary prothrombin deficiency in Indian patients: identification of a novel Ala362 --> Thr (Prothrombin Vellore 1) mutation. J Thromb Haemost. 2005 Jul;3(7):1446-53. doi: 10.1111/j.1538-7836.2005.01402.x. PMID: 15892853.
• Jayandharan G, Shaji RV, Nair SC, Chandy M, Srivastava A. Novel missense mutations in two patients with factor XI deficiency (Val271Leu and Tyr351Ser) and one patient with combined factor XI and factor IX deficiency (Phe349Val). J Thromb Haemost. 2005 Apr;3(4):808-11. doi: 10.1111/j.1538-7836.2005.01230.x. PMID: 15842381.
• Edison ES, Shaji RV, Srivastava A, Chandy M. Compound heterozygosity for Hb E and Hb Lepore-Hollandia in India; first report and potential diagnostic pitfalls. Hemoglobin. 2005;29(3):221-4. doi: 10.1081/hem-200066327. PMID: 16114186.
• Edison ES, Shaji RV, Srivastava A, Chandy M. Hyperbilirubinemia in homozygous HbE disease is associated with the UGT1A1 gene polymorphism. Hemoglobin. 2005;29(3):189-95. doi: 10.1081/hem-200066314. PMID: 16114182.
• Edison ES, Shaji RV, Devi SG, Kumar SS, Srivastava A, Chandy M. Hb Showa-Yakushiji [beta110(G12)Leu-->Pro] in four unrelated patients from west Bengal. Hemoglobin. 2005;29(1):19-25. PMID: 15768552.
• Raghuraman S, Abraham P, Sridharan G, Daniel HD, Ramakrishna BS, Shaji RV. HCV genotype 4--an emerging threat as a cause of chronic liver disease in Indian (south) patients. J Clin Virol. 2004 Dec;31(4):253-8. doi:10.1016/j.jcv.2004.03.019. PMID: 15494265.
• Sathish N, Abraham P, Peedicayil A, Sridharan G, Shaji RV, Chandy G. E2 sequence variations of HPV 16 among patients with cervical neoplasia seen in the Indian subcontinent. Gynecol Oncol. 2004 Nov;95(2):363-9. doi: 10.1016/j.ygyno.2004.08.025. PMID: 15491758.
• Sathish N, Abraham P, Peedicayil A, Sridharan G, John S, Shaji RV, Chandy G. HPV DNA in plasma of patients with cervical carcinoma. J Clin Virol. 2004 Nov;31(3):204-9. doi: 10.1016/j.jcv.2004.03.013. PMID: 15465413.
• Vivekanandan P, Abraham P, Sridharan G, Chandy G, Shaji RV, Daniel D, Raghuraman S, Daniel HD, Subramaniam T. High frequency of the 1896 precore mutation in patients and blood donors with hepatitis B virus infection from the Indian subcontinent. Mol Diagn. 2004;8(1):51-6. doi: 10.1007/BF03260047. PMID: 15230642.Srivastava A, Poonkuzhali B, Shaji RV, George B, Mathews V, Chandy M, Krishnamoorthy R. Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation. Blood. 2004 Sep 1;104(5):1574-7. doi: 10.1182/blood-2003-11-3778. Epub 2004 May 13. PMID: 15142875.
• Venkatraman A, Ramakrishna BS, Shaji RV, Kumar NS, Pulimood A, Patra S. Amelioration of dextran sulfate colitis by butyrate: role of heat shock protein 70 and NF-kappaB. Am J Physiol Gastrointest Liver Physiol. 2003 Jul;285(1):G177-84. doi: 10.1152/ajpgi.00307.2002. Epub 2003 Mar 13. PMID: 12637250.
• Shaji RV, Edison ES, Krishnamoorthy R, Chandy M, Srivastava A. Hb Lepore in the Indian population. Hemoglobin. 2003 Feb;27(1):7-14. doi: 10.1081/hem-120018431. PMID: 12603088.
• Kannangai R, Shaji RV, Ramalingam S, Jesudason MV, Abraham OC, George R, Shanmugam AP, Schwartz DH, Sridharan G. HIV-2 subtype circulating in India (south). J Acquir Immune Defic Syndr. 2003 Jun 1;33(2):219-22. doi: 10.1097/00126334-200306010-00017. PMID: 12794558.
• Shaji RV, Edison ES, Poonkuzhali B, Srivastava A, Chandy M. Rapid detection of beta-globin gene mutations and polymorphisms by temporal temperature gradient gel electrophoresis. Clin Chem. 2003 May;49(5):777-81. doi: 10.1373/49.5.777. PMID: 12709369.
• Gajra B, Bandyopadhyay D, Chakrabarti S, Sengupta B, De M, Shaji RV, Talukder G. Thalassemia beta0 due to an identical frameshift mutation, codon 15 (-T) in both parents. Am J Hematol. 2004 Feb;75(2):117. doi: 10.1002/ajh.10461. PMID: 14755384.
• Jayandharan G, Shaji RV, George B, Chandy M, Srivastava A. Informativeness of linkage analysis for genetic diagnosis of haemophilia A in India. Haemophilia. 2004 Sep;10(5):553-9. doi: 10.1111/j.1365-2516.2004.00908.x. PMID: 15357783.
• Shaji RV, Eunice SE, Baidya S, Srivastava A, Chandy M. Determination of the breakpoint and molecular diagnosis of a common alpha-thalassaemia-1 deletion in the Indian population. Br J Haematol. 2003 Dec;123(5):942-7. doi: 10.1046/j.1365-141.2003.04704.x. PMID: 14632787.
• Jayandharan G, Shaji RV, Chandy M, Srivastava A. Identification of factor IX gene defects using a multiplex PCR and CSGE strategy-a first report. J Thromb Haemost. 2003 Sep;1(9):2051-4. doi: 10.1046/j.1538-7836.2003.00347.x. PMID: 12941051.
• Srivastava A, Usher S, Nelson EJ, Jayandharan G, Shaji RV, Chandy M, Seligsohn U, Peretz H. Prenatal diagnosis of Glanzmann thrombasthenia. Natl Med J India. 2003 Jul-Aug;16(4):207-8. PMID: 14606769.
• Shaji RV, Edison ES, Poonkuzhali B, Srivastava A, Chandy M. Rapid detection of beta-globin gene mutations and polymorphisms by temporal temperature gradient gel electrophoresis. Clin Chem. 2003 May;49(5):777-81. doi: 10.1373/49.5.777. PMID: 12709369.
• Shaji RV, Edison ES, Krishnamoorthy R, Chandy M, Srivastava A. Hb Lepore in the Indian population. Hemoglobin. 2003 Feb;27(1):7-14. doi: 10.1081/hem-120018431. PMID: 12603088.
• Shaji RV, Srivastava A, Krishnamoorthy R, Chandy M. Coexistence of a novel beta-globin gene deletion (codons 81-87) with the codon 30 (G-->C) mutation in an Indian patient with beta0-thalassemia. Hemoglobin. 2002 Aug;26(3):237-43. doi: 10.1081/hem-120015027. PMID: 12403488.
• Shaji RV, Gerard N, Krishnamoorthy R, Srivastava A, Chandy M. A novel beta-thalassemia mutation in an Asian Indian. Hemoglobin. 2002 Feb;26(1):49-57. doi: 10.1081/hem-120002940. PMID: 11939512.
• Manayani DJ, Shaji RV, Fletcher GJ, Cherian T, Murali N, Sathish N, Solomon T, Gnanamuthu C, Sridharan G. Comparison of molecular and conventional methods for typing of enteroviral isolates. J Clin Microbiol. 2002 Mar;40(3):1069-70. doi: 10.1128/JCM.40.3.1069-1070.2002. PMID: 11880442; PMCID: PMC120247.
• Mathews V, Balasubramanian P, Shaji RV, George B, Chandy M, Srivastava A. Central nervous system relapse in a patient with acute promyelocytic leukaemia treated with arsenic tri-oxide. Br J Haematol. 2001 Apr;113(1):257-8. doi: 10.1046/j.1365-2141.2001.02673-4.x. PMID: 11360894.
• Shaji RV, Srivastava A, Krishnamoorthy R, Chandy M. Coexistence of a novel beta-globin gene deletion (codons 81-87) with the codon 30 (G-->C) mutation in an Indian patient with beta0-thalassemia. Hemoglobin. 2002 Aug;26(3):237-43. doi: 10.1081/hem-120015027. PMID: 12403488.
• Mathews V, Balasubramanian P, Shaji RV, George B, Chandy M, Srivastava A. Arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: a single center experience. Am J Hematol. 2002 Aug;70(4):292-9. doi: 10.1002/ajh.10138. PMID: 12210810.
• Shaji RV, Gerard N, Krishnamoorthy R, Srivastava A, Chandy M. A novel beta- thalassemia mutation in an Asian Indian. Hemoglobin. 2002 Feb;26(1):49-57. doi: 10.1081/hem-120002940. PMID: 11939512.
• Mathews V, Balasubramanian P, Shaji RV, George B, Chandy M, Srivastava A. Central nervous system relapse in a patient with acute promyelocytic leukaemia treated with arsenic tri-oxide. Br J Haematol. 2001 Apr;113(1):257-8. doi: 10.1046/j.1365-2141.2001.02673-4.x. PMID: 11360894.
• Shaji RV, Srivastava A, Chandy M, Krishnamoorthy R. A single tube multiplex PCR method to detect the common alpha+ thalassemia alleles. Blood. 2000 Mar 1;95(5):1879-80. PMID: 10744390.
• George K, George SS, James C, Fernandes HA, Shaji RV, Srivastava A, Chandy M. Transvaginal chorionic villus sampling-an alternative approach. Aust N Z J Obstet Gynaecol. 1999 Nov;39(4):487-9. doi: 10.1111/j.1479-828x.1999.tb03140.x. PMID: 10687771.
• Muralitharan S, Srivastava A, Shaji RV, Mathai M, Srivastava VM, Dennison D, Lu CY, Krishnamoorthy R. Prenatal diagnosis of beta-thalassaemia mutations using the reverse dot blot technique. Natl Med J India. 1996 Mar-Apr;9(2):70-1. Erratum in: Natl Med J India 1996 May-Jun;9(3):150. PMID: 8857041.

Pre-clinical lentiviral gene therapy

Dr. Alok Srivastava, Centre for Stem Cell Research, CMC, Vellore.

Disease modelling of haematological disorders using iPSCs

Dr. Biju George, Department of Haematology, CMC, Vellore.

Dr. Poonkuzhali Balasubramanian, Department of Haematology, CMC, Vellore.

• Kannan V Manian

  PhD Student (2009-2017)

  Current position: Post Doctoral Fellow

  Ocular Genomics Institute, Harvard Medical School

  Boston, Massachusetts, USA.

• Janakiram Rayabaram

  PhD Student (2009-2015)

  Current position: Scientist - I, Aurigene Discovery Technologies Limited, Bangalore.

• Nancy Beryl Janette

  PhD Student (2009-2015)

  Current position: Lecturer, Department of Haematology, Christian Medical College, Vellore.

• Syed Mohammed Musheer Aalam

  PhD Student (2009-2016)

  Current position: Post doctoral research fellow, Mayo clinic, Rochester.

• Thiyagaraj M

  PhD Student (2009-2016)

  Current position: Post doctoral research fellow, St Jude Children's research hospital, Memphis.

• Sumitha Prameela Bharathan

  PhD Student (2009-2016)

  Current position:Post Doctoral Research Fellow

  Ophthalmology, Children’s Hospital Los Angeles

  Los Angeles, California, USA.

• Aneesha Nath

  PhD Student (2014-2020)

  Current position: Post Doctoral Fellow

  Department of Pediatrics, University of Florida.

• Vasanth Thamodaran

  Post-Doctoral Research (2017-2020)

  Current position: Senior Scientist

  Tata Institute for Genetics and Society

  NCBS, Bengaluru, India.

• Abhirup Bagchi

  PhD Student (2017-2023)

  Current position: Post-Doctoral Research

  Department of Paediatrics

  Perelman School of Medicine

  University of Pennsylvania, US

"Contents will be updated soon."