Staff >> Faculty >> Dr. G. Jayandharan

Dr. G. Jayandharan, MSc, PhD

Associate Professor, Haematology

Career Interests

Gene therapy, Molecular haemostasis

Research Support

• Department of Biotechnology, Government of India
• Department of Science and Technology, Government of India
• Bayer Healthcare, USA

Research

Department of Biotechnology, Government of India
Department of Science and Technology, Government of India
Bayer Healthcare, USA

Molecular Haemostasis

We are studying the molecular basis of rare coagulation deficiencies such as factor (F) I, prothrombin, F5, F5+F8, F7, F10, F11 and F13 deficiency and establishing algorithms for the genetic diagnosis in these conditions. In addition we are also elucidating the role of various molecular regulators of blood induced joint damage in preclinical models of haemophilia.

Gene Therapy

The collective experience with Adeno-associated virus (AAV) vector mediated human gene therapy trials so far, have clearly pointed to the need for substantial improvement in the efficiency of AAV mediated transgene expression as well as the need to attenuate the capsid-or transgene specific innate or adaptive immune responses against these vectors to achieve successful long-term gene transfer. Thus the research in this sub-theme is focused on dissecting out the biology of AAV life-cycle by understanding the interactions between AAV and various host cellular proteins, use this knowledge to design strategies to either augment the efficiency of gene transfer or intervene with (immune response) processes which are detrimental to AAV’s survival, yet maintain the safety of these interventionist strategies to the host cellular environment. These strategies are being simultaneously tested for their efficacy and safety in therapeutic models (Figure).

Educations

Degree	Year
Post-doctoral Fellow - 2007-2009, Dr Arun Srivastava’s Laboratory, Powell Gene Therapy Center, University of Florida, Gainesville, USA.	2007-2009
PhD [Biomedical sciences/ Molecular Biology]-2008, T.N Dr. MGR Medical University, Chennai, India.	2003-2008
M.Sc [Microbiology]- 1999, Madras University, Chennai, India.	1997-1999

Professional Experience

Year	Professional Experience
2013	Associate Professor, Department of Hematology, Christian Medical College, Vellore,India
2012	Department of Hematology, Christian Medical College, Vellore, India
2010	Adjunct Scientist, Center for Stem Cell Research, Christian Medical College, Vellore,India
2008 - 2012	Lecturer/Assistant Professor, Department of Hematology, Christian Medical College, Vellore, India
2007 - 2009	Post Doctoral Associate, Department of Pediatrics, University of Florida, Gainesville, USA
2001-2008	Lecturer (MSc), Department of Hematology, Christian Medical College, Vellore, India

Awards

Year	Awards
2014-17	Senior Innovative Young Biotechnologist award, Department of Biotechnology, Government of India
2014	Young scientist award, YIM-MIT Boston, USA
2012	DST travel award to attend American Society for Haematology meeting.
2012	Swarnajayanti Fellowship award, Department of Science and Technology, Government of India
2011	Innovative Young Biotechnologist award, Department of Biotechnology, Government of India
2011	Eberhard Mammen Young Investigator award, Thieme Publishers.
2010	Bayer Hemophilia Early Career Investigator Award, Bayer Inc, USA
2009	Travel award, 12th American Society of Gene Therapy meeting, San Diego, USA
2006	Overseas associate fellowship, Department of Biotechnology, Government of India
2003	Aventis Travel grant, International Society of Thrombosis and Hemostasis XIX congress, Birmingham, U.K.
1999	First rank in Madras University during Masters in Microbiology

Recognitions

Year	Recognitions
2014-17	Invited Member, Hematology and immunology gene and cell therapy Committee, American Society of gene and Cell Therapy, Washington DC, USA.
2011 - Present	Invited Member, Laboratory Sciences Technical Committee, World Federation of Hemophilia, Montreal, Canada.

Invited Talks

Year	Invited Talks
2014, Mar-17	National Seminar on Biotechnology, Pondicherry University, Pondicherry.
2014, Mar-14	School of Biological Sciences, Karunya University, Coimbatore
2014, Feb-28	Plenary lecture, National Seminar on Stem Cells and tissue engineering, Vels University, Chennai.
2014, Feb-25	School of Biotechnology and Technology, VIT University, Vellore
2014, Feb-20	Stem Cell biology Seminar series, NiRRH - Mumbai.
2014, Feb-19	NSF colloquium, TIFR-Mumbai
2014, Jan-16	School of Engineering, Biotechnology / Bioengineering seminar, IIT - Kanpur
2013, Dec-24	All India Cell Biology Conference, IISc, Bengaluru
2013, Sep-30	Seminar in Biotechnology, KSR College, Tiruchengode
2013, July-26	School of Biotechnology Research Seminar Series, VIT University
2013, May-24	National Seminar on Drug discovery, JSS College, Ooty
2013, May-18	National Seminar on Modern Biotechnology: concepts and practice, Madurai Kamaraj University
2013, Apr-19	Musculoskeletal Congress, World Federation of Hemophilia, Chicago
2013, Mar-27	Advanced School in Biomedical Nanotechnology, SASTRA University, Tanjore
2012, July-9	Invited Chair on Session on genetics, World Federation of Hemophilia, Congress, Paris
2012, Sep-10	Emerging trends in Cancer and Stem Cell biology, Bharathidasan University, Trichy
2011, Nov-4	European Society of Hematology Annual Highlights meeting, Bangalore
2011, Nov-11	Indian Society of Hematology and Blood Transfusion meeting, Chandigarh
2010, Mar-2	Harvard University-NCBS Stem Cell Initiative, Bangalore
2010, July 13	Hemophilia 2010 world congress, Buenos Aires
2010, Nov-18	Indian Society of Hematology and Blood Transfusion meeting, Kolkata
2006, May-21	Hemophilia 2006 world congress, Vancouver
2004, Oct-20	Hemophilia 2004 world congress, Bangkok

Honors

Year	Honors
2013	Oral presentation, International Society of Thrombosis and Hemostasis XXIV congress at Amsterdam, Netherlands
2011	Oral presentation, 14th American Society of Gene and Cell Therapy meeting, Seattle, USA.
2010	Oral presentation, 52nd Annual Meeting of the American Society of Hematology, Orlando, USA
2009	Abstract achievement award and Oral presentation, 12th American Society of Gene Therapy meeting, San Diego, USA
2008	Oral presentation, 11th Annual Meeting of the American Society of Gene Therapy, Boston, USA

Professional Membership

Year	Professional Membership
2011-present	Member, International Society for Thrombosis and Hemostasis
2010- present	Member, European Society for Gene and Cell Therapy
2010- present	Indian Society for Hematology and Transfusion Medicine
2007-present	Member, American Society for Gene and Cellular Therapy

Ad Hoc Reviewer

2010 - present

• Molecular Therapy
• Annals of Hematology
• Journal of Genetic Syndromes and Gene Therapy
• Thrombosis Research
• Haemophilia Journal
• Journal of Thrombosis and Haemostasis
• Gene Therapy
• FEBS journal

Contact Details

Dr. G. Jayandharan, MSc, PhD Associate Professor

Email: [email protected]
Phone: +91 416 2284118/3562

Publications

• Sen D, Balakrishnan B, Jayandharan GR. Cellular unfolded protein response against viruses used in gene therapy. Front Microbiol 2014; in press
• Selot R, Hareendran S, Jayandharan GR. Developing immunologically inert adeno-associated virus (AAV) vectors for gene therapy: possibilities and limitations. Curr Pharm Biotechnol 2014; in press.
• Balakrishnan B, Jayandharan GR. Basic biology of Adeno-associated virus (AAV) vectors used in gene therapy. Curr Gene Ther 2014; in press.
• Ramesh B. Batchu, Oksana V. Gruzdyna, Amberly M. Moreno-Bost, Susann Szmania, Jayandharan GR, Arun Srivastava, Bala K. Kolli, Donald W. Weaver, Frits van Rhee, Scott A. Gruber. Efficient lysis of epithelial ovarian cancer cells by MAGE-A3-induced cytotoxic T lymphocytes using rAAV-6 capsid mutant vector. Vaccine 6 January 2014 [Epub ahead of print].
• Jain R, T L, Chandran J, Jayandharan GR, Palle A, Moses PD. A novel mutation c.1048A>T at codon 350(Lys>Stop) in PROC gene causing neonatal purpura fulminans. Blood Coagul Fibrinolysis. 2013; 24:890-2.
• Devi GS, Arora N, Rajkumar SV, Edison ES, Srivastava A, Jayandharan GR*. Fluorescent PCR-based gene dose analysis for detection of deletion mutations in carriers of haemophilia. Haemophilia. 2013 Jul 16. doi: 10.1111/hae.12233.
• Sangeetha H, Balakrishnan B, Sen D, Kumar S, Srivastava A, Jayandharan GR*. Adeno-associated virus (AAV) vectors in gene therapy: Immune challenges and strategies to circumvent them. Rev Med Virol; 2013, in press.
• Sen D, Balakrishnan B, Gabriel N, Agrawal P, Roshini V, Samuel R, Srivastava A, Jayandharan GR. Improved adeno-associated virus (AAV) serotype 1 and 5 vectors for gene therapy. Sci Rep; 2013, 3: 1832. DOI: 10.1038/srep01832.
• Song L, Kauss MA, Kopin E, Chandra M, Ul-Hasan T, Miller E, Jayandharan GR,Rivers AE, Aslanidi GV, Ling C, Li B, Ma W, Li X, Andino LA, Zhong L, Tarantal AF, Yoder MC, Wong KK, Jr, Tan M, Chatterjee S, Srivastava A. Optimizing the transduction efficiency of human hematopoietic stem cells using capsid-modified AAV6 vectors in vitro and in a xenograft mouse model in vivo. Cytotherapy 2013, in press.
• Sumitha E, Jayandharan GR, Neeraj A, David S, Sankari Devi G, ShenbagaPriya P, Nair SC, George B, Viswabandya A, Mathews V, Chandy M, Srivastava A. Molecular basis of fibrinogen deficiency in 25 patients from India. Haemophilia2013, in press.
• Sen D, Gadkari RA, Sudha G, Gabriel N, Sathish Kumar Y, Selot R, Samuel R, Rajalingam S, Ramya V, Nair SC,Srinivasan N, Srivastava A, Jayandharan GR. Targeted modifications in adeno-associated virus (AAV) serotype -8 capsid improves its hepatic gene transfer efficiency in vivo. Hum Gene Ther Methods2013; in press.
• Gabriel N, Hareendran S, Sen D, Gadkari RA, Govindarajan S, Hussain M, Duraiswamy R, Samuel R, Srinivasan N, Srivastava A, Jayandharan GR. Bio-Engineering of Adeno-Associated Virus Serotype (AAV)-2 Capsid at Serine/Threonine/Lysine Residues Improves Its Transduction Efficiency Both In Vitro and In Vivo. Hum Gene Ther Methods 2013; in press.
• Balakrishnan B, Sen D, David S, Srivastava A, Srivastava A, Jayandharan GR. Activation of the Cellular Unfolded Protein Response by Recombinant Adeno-Associated Virus Vectors. PLoS ONE 2013; 8(1): e53845. doi:10.1371/journal.pone.0053845.
• Sen D, Chapla A, Walter N, Daniel V, Srivastava A, Jayandharan GR. Nuclear Factor (NF)-κB is a major regulator of blood induced joint damage in a murine model of hemophilia. J Thromb Haemost 2013, 11: 293-306.
• Song L, Li X, Jayandharan GR, Wang Y, Aslanidi GV, Ling C, Zhong L, Gao G, Yoder MC, Ling C, Tan M, Srivastava A. High-efficiency transduction of primary human hematopoietic stem cells and erythroid lineage-restricted expression by optimized AAV6 serotype vectors in vitro and in a murine xenograft model in vivo. PLoS ONE 2013; in press.
• Goodeve AC, Perry DJ, Cumming T, Hill M, Jennings I, Kitchen S, Walker I, Gray E, Jayandharan G, Tuddenham E. Genetics of Haemostasis. Haemophilia 2012; 18: S4, 73-80.
• David S, Jayandharan GR*, Abraham A, Rr J, 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 doi: 10.1111/j.1600-0609.2012.01818.
• Jayandharan GR*, Srivastava A, Srivastava A. Application of molecular genetics in haemophilia: from diagnoses to therapy. Sem Thromb Haemost 2012; in press.
• Jayandharan GR*, Srivastava A. Hemophilia: genetics, diagnosis and management. J Genet Syndr Gene Ther; 2012, doi:10.4172/2157-7412.S1-005.
• Zhong L, Jayandharan GR, Aslanidi GV, Zolotukhin S, Herzog RW, Srivastava A. Development of novel recombinant AAV Vectors and strategies for the potential gene therapy of hemophilia. J Genet Syndr Gene Ther; 2012, doi.org/10.4172/2157-7412.S1-008.
• Aslanidi GV, Rivers AE, Ortiz L, Govindasamy L, Ling C, Jayandharan GR, Zolotukhin S, Agbandje-McKenna M, Srivastava A. High-efficiency transduction of human monocyte-derived dendritic cells by capsid-modified recombinant AAV2 vectors. Vaccine. 2012; in press.
• Jayandharan GR, Aslanidi G, Martino AT, Jahn SC, Perrin GQ, Herzog RW, Srivastava A. Activation of the NF-kB pathway by AAV vectors and its implications in immune response and gene therapy Proc Natl Acad Sci USA 2011; 108: 3743-8.
• Rogers GL, Martino AT, Aslanidi G, Jayandharan GR, Srivastava A, Herzog RW. Innate immune responses to AAV vectors. Front Microbiol, 2011; 2: e194.
• Sumitha E, Jayandharan GR*, David S, Jacob RR, Sankari Devi G, Nair SC, George B, Viswabandya A, Mathews V, Chandy M, Srivastava A. Molecular basis of Bernard Soulier syndrome in 27 unrelated patients in India: Identification of four common ancestral mutations and their genotype-phenotype correlations. J Thromb Haemost 2011; 9: 1590-8.
• Chapla A, Jayandharan GR*, Sumitha E, Sankari Devi G, Nair SC, George B, Mathews V, Chandy M, Srivastava A. Genotype-phenotype correlation of hereditary factor V deficiency in India: Thromb Haemost 2011; 105:1120-3.
• Ma W, Li B, Ling C, Jayandharan GR, Srivastava A, Byrne BJ. A simple method to increase the transduction efficiency of single-stranded AAV vectors in vitro and in vivo. Hum Gene Ther 2011; 22: 633-40.
• Petrs-Silva H, Dinculescu A, Li Q, Deng WT, Pang JJ, Min SH, Chiodo V, Neeley AW, Govindasamy L, Bennett A, Agbandje-McKenna M, Zhong L, Li B, Jayandharan GR, Srivastava A, Lewin AS, Hauswirth WW. Novel Properties of Tyrosine-mutant AAV2 Vectors in the Mouse Retina. Mol Ther 2011; 19: 293-301.
• Jayandharan GR, Zhong L, Sack BK, Rivers AE, Li M, Li B, Herzog RW, Srivastava A. Optimized AAV-protein phosphatase 5 helper-viruses for efficient transduction by single-stranded AAV vectors: Therapeutic expression of Factor IX at reduced vector doses. Hum Gene Ther 2010; 21: 271-83.
• Preston FE, Lippi G, Favaloro EJ, Jayandharan GR, Edison ES, Srivastava A. Quality issues in laboratory haemostasis. Haemophilia 2010; Suppl 5:93-9.
• Markusic DM, Herzog RW, Aslanidi GV, Hoffman BE, Li B, Li M, Jayandharan GR, Ling C, Zolotukhin I, Ma W, Zolotukhin S, Srivastava A, Zhong L. High-efficiency transduction and correction of murine hemophilia B using AAV2 vectors devoid of multiple surface-exposed tyrosines. Mol Ther 2010; 18: 2048-56.
• Ling C, Lu Y, Kelsi JK, Jayandharan GR, Li B, Ma W, Cheng B, Gee SW, McGoogan KE, Govindasamy L, Agbandje-McKenna M, Zhong L, Srivastava A. Human Hepatocyte Growth Factor Receptor is a cellular Co-Receptor for AAV3. Hum Gene Ther 2010; 21:1741-7.
• Qiao C, Zhang W, Yuan Z, Shin JH, Li J, Jayandharan GR, Zhong L, Srivastava A, Xiao X, Duan D. AAV6 capsid tyrosine to phenylalanine mutations improve gene transfer to skeletal muscle. Hum Gene Ther 2010; 21: 1343-8.
• Li M, Jayandharan GR, Li B, Chen L, Ma W, Srivastava A, Zhong L. High-Efficiency transduction of fibroblasts and mesenchymal Stem Cells by tyrosine-Mutant AAV2 vectors for their potential use in cellular therapy. Hum Gene Ther 2010; 21: 1527-43.
• Jayandharan GR, Nair SC, Poonoose P, Thomas R, John J, Keshav, SK, Cherian RS, Devadharshini 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; 15: 1228-36.
• Lin IJ, Zhou Z, Crusselle-Davis VJ, Moghimi B, Gandhi K, Anantharaman A, Pantic D, Huang S, Jayandharan G, Zhong L, Srivastava A, Bungert J. Calpeptin increases the activity of USF and induces high-level globin gene expression in erythroid cells. J Biol Chem 2009; 284: 20130-5.
• Zhong L, Li B, Jayandharan GR, Mah CS, Govindasamy L, Agbandje-McKenna M, Cooper M, Herzog RW, Zolotukhin I, Warrington KH Jr, Weigel-Van Aken KA, Hobbs JA, Zolotukhin S,Muzyczka N, Srivastava A. Tyrosine phosphorylation of AAV2 vectors and its consequences on viral intracellular trafficking and transgene expression. Virology 2008; 381: 194-202.
• Jayandharan GR, Zhong L, Li B, Kachniarz B, Srivastava A. Strategies for improving the transduction efficiency of single-stranded adenoassociated virus vectors in vitro and in vivo. Gene Ther 2008; 15: 1287-93.
• Jayandharan GR, Srivastava A. Phenotypic heterogeneity in severe hemophilia. Semin Thromb Haemost 2008; 34:128-41.
• Jayandharan G, Spreafico M, Viswabandya A, Chandy M, Srivastava A, Peyvandi F. Mutations in the MCFD2 gene are predominant among patients with hereditary combined FV and FVIII deficiency (F5F8D) in India. Haemophilia 2007, 13: 413-9.
• Jayandharan G, Viswabandya A, Nair SC, Chandy M, Srivastava A. Molecular basis of hereditary factor VII deficiency in India: Five novel mutations including a double missense mutation (Ala191Glu; Trp364Cys) in 11 unrelated patients. Haematologica 2007; 92: 1002-3.
• Jayandharan G, Nelson EJR, Baidya S, Chandy M, Srivastava A. A new multiplex PCR and Conformation Sensitive Gel Electrophoresis strategy for mutation detection in the platelet glycoprotein aIIbb3 genes. J Thromb Haemost 2007; 5: 206-9.
• Thomas M, Jayandharan G, Chandy M. Molecular screening of the neutrophil elastase gene in congenital neutropenia. Indian Pediatr. 2006; 43: 1081-4.
• Peyvandi F, Jayandharan G, Chandy M, Srivastava A, Nakaya SM, Johnson MJ, Thompson AR, Goodeve AC, Garagiola I, Lavoretano S, Menegatti M, Palla R, Spreafico M, Tagliabue L, Asselta R, Duga S, Mannucci PM. Genetic diagnosis of haemophilia and other inherited bleeding disorders. Haemophilia 2006; 12: 82–9.
• Mathews V, Desire S, George B, Lakshmi KM, Rao JG, Viswabandya A, Bajel A, Srivastava VM, Srivastava A, Chandy M. Hepatotoxicity profile of single agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia, its impact on clinical outcome and the effect of genetic polymorphisms on the incidence of hepatotoxicity. Leukemia 2006; 20: 881-3.
• Jayandharan GR, Viswabandya A, Baidya S, Nair SC, George B, Mathews V, Chandy M, Srivastava A. Mutations in coagulation factor XIII A gene in eight unrelated Indians: Five novel mutations identified by a novel PCR-CSGE approach. Thromb Haemost 2006; 95: 551-56.
• Jayandharan GR, Shaji R.V, Baidya S, Nair SC, Chandy M, Srivastava. Molecular characterization of factor IX gene mutations in 53 patients with haemophilia B in India. Thromb Haemost 2005; 94: 883-6.
• 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; 11: 481-91.
• 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; 3: 1482-7.
• Jayandharan GR, Srivastava A, Srivastava A. Application of molecular genetics in haemophilia: from diagnoses to therapy. Sem Thromb Haemost 2012; 38: 64-78.
• Jayandharan GR, Srivastava A. Hemophilia: disease, diagnosis and management. J Genet Syndr Gene Ther; 2012. doi: 10.4172/2157-7412.S1-005.
• Zhong L, Jayandharan GR, Aslanidi G, Zolutukin S, Herzog RW, Srivastava A. Development of Novel Recombinant AAV Vectors and Strategies for the Potential Gene Therapy of Hemophilia J Genet Syndr Gene Ther; 2012. doi: 10.4172/2157-7412.S1-008.
• David S, Jayandharan GR, Abraham A, Rr J, 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 doi: 10.1111/j.1600-0609.2012.01818.
• 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; 3: 1446-53.
• 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; 3: 808–811.
• Jayandharan G, Shaji RV, George B, Chandy M, Srivastava A. Informativeness of linkage analysis for genetic diagnosis of haemophilia A in India. Haemophilia 2004; 10: 553-9.
• Srivastava A, Usher S, Nelson EJR, Jayandharan G, Shaji RV, Chandy M, Seligsohn U, Peretz H. Prenatal diagnosis of Glanzmann thrombasthenia - first report from India. Natl Med J India 2003; 16: 207-8.
• 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; 1: 2051-4.