Centre for Stem Cell Research
Christian Medical CollegeOffice: +91 416 228-5129
Lab: +91 416 228-5132
Fax: +91 416 228-5103
Email: cscrviro@cmcvellore.ac.in
Career Interests
Develop a robust pre-Adeno-associated virus gene therapy antibody screening method with high specificity and sensitivity using cell based and other serological methods for treatment of monogenetic disorders.
Education
- 2009: PhD, Department of Clinical Virology, CMC, Vellore, India.
- 2001: M.Sc Microbiology, Periyar University, Tamil Nadu, India.
Professional Experience
- 2014-till date : Consultant, National EQAS Program, Dept of Clinical Virology, CMC, India
- 2009-2013 : Postdoctoral Fellow, Dept of Pathology, Johns Hopkins School of Medicine
- 2008-2009 : Research Trainee, Dept of Pathology, Johns Hopkins School of Medicine
- 2001-2008 : Associate Research Officer, Dept of Clinical Virology, CMC, India.
Awards
- 2009 : IAMM Gold Medal for Best Published paper in Virology during the year 2009 in National Congress of Indian Association of Medical Microbiologists at Pune, India on Nov., 2009
- 2006 : IAMM Gold Medal for Best Published paper in Virology during the year 2006 in XXXI National Congress of Indian Association of Medical Microbiologists at Kasturba Medical College, Mangalore, India on Nov. 16 – 18, 2007.
Hemophilia is an X-linked blood clotting disorder caused by deficiency in the intrinsic coagulation cascade due to mutations in the hF8 or hF9 genes. Therapy for hemophilia includes administration of exogenous coagulation factors or blood transfusions. The short biological half-life of FVIII protein and development of antibodies against FVIII are serious complications of replacement therapy. On the other hand, gene therapy which is used for monogenetic disorders provides a functional copy of the mutated gene. Gene therapy using adeno-associated viral (AAV) vectors for hemophilia A and B has shown good success in preclinical and clinical studies.
AAV which belongs to the Parvoviridae family, genus Dependovirus is classified into 13 serotypes that differ in their structures of capsids. Their lack of pathogenicity, the persistent expression of the transgene, and the availability of many serotypes have made AAV an important gene therapy vector. However, the presence of anti-AAV antibodies due to natural infection or significant-reactivity between serotypes against the capsid antigen is a significant obstacle in using AAV as a gene therapy vector. Extremely low titers of neutralizing antibodies (NAb) can neutralize the vector and reduce the efficiency of the gene expression of the vector making gene therapy ineffective.
We study the humoral immune response against AAV which is classified into neutralizing and binding antibodies. We are working on developing practical and reproducible technologies for determining the titers of pre-existing AAV antibodies with assays that have good sensitivity and specificity. Widely used current techniques for the detection of anti-AAV antibodies are capsid ELISA and transduction inhibition assay (TIA). While TIA detects neutralizing antibody titer, capsid ELISA detects total antibodies (both neutralizing and non-neutralizing or capsid binding).
Joseph Joel N
Technician
E-mail:cscrviro@cmcvellore.ac.in
Research Interests:
Education: B.Sc - Medical Laboratory Technology, CMC, Vellore.
Farzana J
Technician
E-mail:cscrviro@cmcvellore.ac.in
Research Interests:
Education: B.Sc - Microbiology, Auxilium College, Vellore.
Selected Publications
Journal
- Ramachandran J, Eapen CE, Kang G, Abraham P, Hubert DD, Kurian G, Hephzibah J, Mukhopadhya A, Chandy GM. Hepatitis E superinfection produces severe decompensation in patients with chronic liver disease. J Gastroenterol Hepatol. 2004; 19: 134-8.
- 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: 51-6.
- 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; 31: 253-8.
- Daniel HD, Warier A, Abraham P, Sridharan G. Age-wise exposure rates to hepatitis e virus in a southern Indian patient population without liver disease. Am J Trop Med Hyg. 2004; 71: 675-8.
- Vivekanandan P, Abraham P, Sridharan G, Chandy G, Daniel D, Raghuraman S, Daniel HD, Subramaniam T. Distribution of hepatitis B virus genotypes in blood donors and chronically infected patients in a tertiary care hospital in southern India. Clin Infect Dis. 2004; 38(9): e81-6. Epub 2004 Apr 09.
- Raghuraman S, Abraham P, Daniel HD, Ramakrishna BS, Sridharan G.Characterization of soluble FAS, FAS ligand and tumour necrosis factor-alpha in patients with chronic HCV infection. J Clin Virol. 2005; 34: 63-70.
- Daniel HD, Abraham P, Raghuraman S, Vivekanandan P, Subramaniam T, Sridharan G. Evaluation of a rapid assay as an alternative to conventional enzyme immunoassays for detection of hepatitis C virus-specific antibodies. J Clin Microbiol. 2005; 43: 1977-8.
- Daniel HD, Vivekanandan P, Raghuraman S, Sridharan G, Chandy GM, Abraham P. Significance of the hepatitis C virus (HCV) core antigen as an alternative plasma marker of active HCV infection. Indian J Med Microbiol. 2007; 25: 37-42.
- Vivekanandan P, Bissett S, Ijaz S, Teo CG, Sridharan G, Raghuraman S, Daniel HD, Kavitha ML, Daniel D, Chandy GM, Abraham P. Correlation between hepatitis B genotypes, 1896 precore mutation, virus loads and liver dysfunction in an Indian population. Indian J Gastroenterol. 2008; 27: 142-7.
- Kannangai R, Kandathil AJ, Daniel HD, Prasannakumar S, Lionel J, Abraham P. An unusual seroconversion profile in a pregnant woman infected with the human immunodeficiency virus-1: need for using later generations HIV screening assays. Indian J Med Microbiol. 2008; 26: 390-2.
- Moorthy M, Daniel HD, Kurien G, Abraham P. An evaluation of saliva as an alternative to plasma for the detection of hepatitis C virus antibodies. Indian J Med Microbiol. 2008; 26: 327-32.
- Daniel HD, David J, Grant PR, Garson JA, Chandy GM, Abraham P. Whole blood as an alternative to plasma for detection of hepatitis C virus RNA. J Clin Microbiol. 2008; 46: 3791-4.
- Daniel HD, Grant PR, Garson JA, Tedder RS, Chandy GM, Abraham P. Quantitation of hepatitis C virus using an in-house real-time reverse transcriptase polymerase chain reaction in plasma samples. Diagn Microbiol Infect Dis. 2008; 61: 415-20.
- Vivekanandan P, Daniel HD, Raghuraman S, Daniel D, Shaji RV, Sridharan G, Chandy G, Abraham P. Novel digestion patterns with hepatitis B virus (HBV) strains from the Indian subcontinent detected using restriction fragment length polymorphism. Indian J Med Microbiol. 2008; 26: 96-7.
- Abraham R, Ramakrishna B, Balekuduru A, Daniel HD, Abraham P, Eapen CE, Kurian G. Clinicopathological features and genotype distribution in patients with hepatitis C virus chronic liver disease. Indian J Gastroenterol. 2009; 28: 53-8.
- Sachithanandham J, Ramamurthy M, Kannangai R, Daniel HD, Abraham OC, Rupali P, Pulimood SA, Abraham AM, Sridharan G. Detection of opportunistic DNA viral infections by multiplex PCR among HIV infected individuals receiving care at a tertiary care hospital in South India. Indian J Med Microbiol. 2009; 27: 210-6.
- Daniel HD, Fletcher JG, Chandy GM, Abraham P. Quantitation of hepatitis B virus in plasma using a sensitive cost-effective “in-house” real-time PCR assay. Indian J Med Microbiol. 2009; 27: 111-5.
- Yeh MM, Daniel HD, Torbenson M. Hepatitis C-associated hepatocellular carcinomas in non-cirrhotic livers. Mod Pathol. 2010; 23: 276-83.
- David J, Rajasekar A, Daniel HD, Ngui SL, Ramakrishna B, Zachariah UG, Eapen CE, Abraham P. Infection with hepatitis C virus genotype 3--experience of a tertiary health care centre in south India. Indian J Med Microbiol. 2010; 28: 155-7.
- Vivekanandan P, Daniel HD, Kannangai R, Martinez-Murillo F, Torbenson M. Hepatitis B virus replication induces methylation of both host and viral DNA. J Virol. 2010; 84: 4321-9.
- Vivekanandan P, Daniel H, Yeh MM, Torbenson M. Mitochondrial mutations in hepatocellular carcinomas and fibrolamellar carcinomas. Mod Pathol.2010; 23: 790-8.
- Ross HM, Daniel HD, Vivekanandan P, Kannangai R, Yeh MM, Wu TT, Makhlouf HR, Torbenson M. Fibrolamellar carcinomas are positive for CD68. Mod Pathol. 2011; 24: 390-5.
- Li M, Zhao H, Zhang X, Wood LD, Anders RA, Choti MA, Pawlik TM, Daniel HD, Kannangai R, Offerhaus GJ, Velculescu VE, Wang L, Zhou S, Vogelstein B, Hruban RH, Papadopoulos N, Cai J, Torbenson MS, Kinzler KW. Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma. Nat Genet. 2011; 43: 828-29.
- Wood LD, Heaphy CM, Daniel HD, Naini BV, Lassman CR, Arroyo MR, Kamel IR, Cosgrove DP, Boitnottophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features. Mod Pathol. 2013 May 3. [Epub ahead of print].
- Karagkounis G, Torbenson MS, Daniel HD, Azad NS, Diaz LA Jr, Donehower RC, Hirose K, Ahuja N, Pawlik TM, Choti MA. Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases. Cancer. 2013; 119: 4137-44.
- Daniel HD, & Torbenson M. Transgenic hepatitis B: a new model of HBV infection. Scientific reports. 2017; 7(1), 2610. https://doi.org/10.1038/s41598-017-02862-2.
- Daniel HD, David J, Raghuraman S, Gnanamony M, Chandy GM, Sridharan G, Abraham P. Comparison of Three Different Hepatitis C Virus Genotyping Methods: 5'NCR PCR-RFLP, Core Type-Specific PCR, and NS5b Sequencing in a Tertiary Care Hospital in South India. J Clin Lab Anal. 2017;3:e22045. doi: 10.1002/jcla.22045.
- Daniel HDJ, Kumar S, Kannangai R, Lakshmi KM, Agbandje-McKenna M, Coleman KE, Srivastava A, Srivastava A, Abraham AM. Prevalence of AAV3 capsid binding and neutralizing antibodies in healthy and individuals with hemophilia B from India. Hum Gene Ther. 2020 Nov 18. doi: 10.1089/hum.2020.258. Epub ahead of print. PMID: 33207962.'
Patent
- Torbenson M., Daniel HD. 2015 Transgenic Hepatitis B Virus (HBV): A new model of HBV infection identifies UQCR10 as a viral replication factor. WO 2015/057919 A1.