BIOGRAPHICAL SKETCH. Science

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1 BIOGRAPHICAL SKETCH NAME: DR. LUKE ELIZABETH HANNA era COMMONS USER NAME (credential, e.g., agency login): HANNALE POSITION TITLE: Scientist E EDUCATION/TRAINING INSTITUTION AND LOCATION DEGREE (if applicable) Completion Date MM/YYYY FIELD OF STUDY Stella Maris College (Autonomous), Madras University, Chennai Bachelor of Science Zoology Dr. ALM Post-graduate Institute of Basic Medical Sciences, Madras University, Chennai Master Science of Bio-medical Genetics National Institute for Research in Tuberculosis, The Tamilnadu Dr. MGR Medical University, Chennai Doctor of Philosophy Basic Medical Sciences Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York Postdoctoral Research Fellowship Molecular Virology A. Personal Statement I have a background in Immunology with more than 20 years of working experience in the broad area of immunopathogenesis of infectious diseases and have undertaken a number of research studies on host immune responses to pulmonary and extrapulmonary tuberculosis, HIV infection and HIV/TB coinfection. I have also been trained in molecular virology of HIV. My research interests include identification of cellular biomarkers for predicting TB disease progression and treatment response, identification of factors contributing to the increased risk of TB reactivation among HIV-infected individuals, understanding the unique molecular and biological characteristics of transmitted founder viruses and investigating factors and mechanisms that contribute to resistance to HIV infection among HIV-exposed seronegative individuals. I have had a number of collaborations with researchers from within and outside the country and have successfully administered several projects funded by National and International agencies. I am in charge of the ICMR Biomedical Informatics Division and Regional Reference Labs for molecular diagnosis for the National Early Infant Diagnosis Program and HIV-1 Viral load Testing for NACO at NIRT. I also co ordinate WHOResNet activities and in-country EQA program for cryopreservation of peripheral blood mononuclear cells at NIRT. I am a registered guide for Ph.D. program with the University of Madras and possess the expertise, training and motivation necessary to successfully carry out high quality research.

2 B. Positions and Honors Research Assistant, National Institute for Research in Tuberculosis, Chennai Scientist B, National Institute for Research in Tuberculosis, Chennai Scientist C, National Institute for Research in Tuberculosis, Chennai Scientist D, National Institute for Research in Tuberculosis, Chennai 2016-current Scientist E, National Institute for Research in Tuberculosis, Chennai C. Contribution to Science I have been actively involved in research aimed at understanding the host immune response to TB, and TB with HIV and helminth co-infections, and identification of biomarkers for disease progression and treatment response. The other aspect of my study focuses on characterizing the unique features of HIV- 1 subtype C isolates circulating in the Indian population. Some interesting observations have been made in this line and they have resulted in some recent publications. I have also been involved in the design and development of some clinically and scientifically relevant databases such as TB Drugs, Mycobacterium tuberculosis Structure Data base (MtbSD) and Database of drug targets for resistant pathogens (DDTRP). Publications during the last 5 years ( ) 1. The Role of N-Acetyl Transferases on Isoniazid Resistance from Mycobacterium tuberculosis and Human: An In Silico Approach. Unissa AN, Sukumar S, Hanna LE. Tuberc Respir Dis (Seoul) Jul;80(3): Analysis of interactions of clinical mutants of catalase-peroxidase (KatG) responsible for isoniazid resistance in Mycobacterium tuberculosis with derivatives of isoniazid. Unissa AN, Doss C GP, Kumar T, Swathi S, Lakshmi AR, Hanna LE. J Glob Antimicrob Resist Jul 22. pii: S (17) Molecular mechanisms of action, resistance, detection to the first-line anti tuberculosis drugs: Rifampicin and pyrazinamide in the post whole genome sequencing era. Nusrath Unissa A, Hanna LE. Tuberculosis (Edinb) Jul;105: Pathophysiology of CD4+ T-Cell Depletion in HIV-1 and HIV-2 Infections. Vidya Vijayan KK, Karthigeyan KP, Tripathi SP, Hanna LE. Front Immunol May 23;8: Differential Codon Usage Pattern of HIV-1 tat Gene in Those with Slower and Faster Rates of Disease Progression. Vidyavijayan KK, Anangi B, Banu B, Thiruvengadam K, Hassan S, Hanna LE. AIDS Res Hum Retroviruses Sep;33(9): Cheedarla N, Precilla KL, Babu H, Vijayan KKV, Ashokkumar M, Chandrasekaran P, Kailasam N, Sundaramurthi JC, Swaminathan S, Buddolla V, Vaniambadi SK, Ramanathan VD, Hanna LE. Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals. Sci Rep Apr 24;7: Ashokkumar M, Nesakumar M, Narayanaiah C, Kk VV, Hemalatha B, Tripathy SP, Hanna LE. Molecular characteristics of the envelope of vertically transmitted HIV-1 strains from infants with HIV infection. AIDS Res Hum Retroviruses Aug;33(8): Krishnamoorthy E, Hassan S, Hanna LE, Padmalayam I, Rajaram R, Vishwanathan V. Homology modeling of Homo sapiens Lipoic acid Synthase: substrate docking and insights on its binding mode. J Theor Biol Oct 4. pii: S (16) Unissa AN, Subbian S, Hanna LE, Selvakumar N. Overview on mechanisms of isoniazid action and resistance in Mycobacterium tuberculosis. Infect Genet Evol Sep 6. pii: S (16)

3 10. Vidya V, Hassan S, Precilla LK, Manickam A, Chandrasekeran P, Swaminathan S, Hanna LE. Biased nucleotide composition and differential codon usage pattern in HIV-1 and HIV-2. AIDS Res Hum Retroviruses Sep Sundaramurthi JC, Hanna LE, Selvaraju S, Brindha S, Joel Gnanadoss J, Vincent S, Singh H, Swaminathan S. TBDRUGS - Database of drugs for tuberculosis. Tuberculosis (Edinb) Sep;100: Aralaguppe SG, Siddik AB, Manickam A, Ambikan AT, Kumar MM, Fernandes SJ, Amogne W, Bangaruswamy DK, Hanna LE, Sonnerborg A, Neogi U. Multiplexed next-generation sequencing and de novo assembly to obtain near full-length HIV-1 genome from plasma virus. J Virol Methods Oct;236: Saadhali SA, Hassan S, Hanna LE, Ranganathan UD, Kumar V. Homology modeling, substrate docking, and molecular simulation studies of mycobacteriophage Che12 lysin A. J Mol Model Aug;22(8): Ashokkumar M, Tripathy SP, Hanna LE. Variability in V1V2 and PNGs in pediatric HIV-1 viral variants transmitted through vertical route. AIDS Res Hum Retroviruses 2016 Oct/Nov;32(10-11): Nusrath Unissa A, Hassan S, Indira Kumari V, Revathy R, Hanna LE. Insights into RpoB clinical mutants in mediating rifampicin resistance in Mycobacterium tuberculosis. J Mol Graph Model Jun;67: Gupte A, Padmapriyadarsini C, Mave V, Kadam D, Suryavanshi N, Shivakumar SV, Kohli R, Gupte N, Thiruvengadam K, Kagal A, Meshram S, Bharadwaj R, Khadse S, Ramachandran G, Hanna LE, Pradhan N, Gomathy NS, DeLuca A, Gupta A, Swaminathan S; CTRIUMPH Study Team. Cohort for Tuberculosis Research by the Indo-US Medical Partnership (CTRIUMPH): protocol for a multicentric prospective observational study. BMJ Open Feb 25;6(2):e Nusrath Unissa A, Hanna LE, Swaminathan S. A Note on Derivatives of Isoniazid, Rifampicin, and Pyrazinamide Showing Activity Against Resistant Mycobacterium tuberculosis. Chem Biol Drug Des Apr;87(4): Dinesh S, Menon T, Hanna LE, Suresh V, Sathuvan M, Manikannan M. In vitro anti-hiv-1 activity of fucoidan from Sargassum swartzii. Int J Biol Macromol Jan;82: Hassan S, Thangam M, Vasudevan P, Kumar GR, Unni R, Devi PK, Hanna LE. A userfriendly web portal for analyzing conformational changes in structures of Mycobacterium tuberculosis. J Mol Model Oct;21(10): Prabu A, Hassan S, Prabuseenivasan, Shainaba AS, Hanna LE, Kumar V. Andrographolide: A potent antituberculosis compound that targets Aminoglycoside 2'-N-acetyltransferase in Mycobacterium tuberculosis. J Mol Graph Model Sep;61: Hanna LE, Siromany VA, Annamalai M, Karunaianantham R, Swaminathan S. Challenges in the Early Diagnosis of HIV Infection in Infants: Experience from Tamil Nadu, India. Indian Pediatr Apr;52(4): Unissa AN, Selvakumar N, Narayanan S, Suganthi C, Hanna LE. Investigation of Ser315 Substitutions within katg Gene in Isoniazid-Resistant Clinical Isolates of Mycobacterium tuberculosis from South India. Biomed Res Int. 2015;2015: George PJ, Kumar NP, Sridhar R, Hanna LE, Nair D, Banurekha VV, Nutman TB, Babu S. Coincident helminth infection modulates systemic inflammation and immune activation in active pulmonary tuberculosis. PLoS Negl Trop Dis Nov 6;8(11):e Kumar NP, Sridhar R, Hanna LE, Banurekha VV, Nutman TB, Babu S. Decreased frequencies of circulating CD4+ T follicular helper cells associated with diminished plasma IL-21 in active pulmonary tuberculosis. PLoS One Oct 24;9(10):e

4 25. Ameeruddin NU, Luke Elizabeth H. Impact of isoniazid resistance on virulence of global and south Indian clinical isolates of Mycobacterium tuberculosis. Tuberculosis (Edinb) Dec;94(6): Kumar NP, Sridhar R, Hanna LE, Banurekha VV, Jawahar MS, NutmanTB, Babu S. Altered CD8+ T cell frequency and function in tuberculous lymphadenitis. Tuberculosis 2014 Jul 1, pii: S (14) Anuradha R, George PJ, Hanna LE and Kumaran P. Expansion of parasite-specific CD4+ and CD8+ T cells expressing IL-10 superfamily cytokine members and their regulation in human lymphatic filariasis. Chandrasekaran V, Nutman TB, Babu S. PLoS Negl Trop Dis Apr 3;8(4):e Anuradha R, George PJ, Hanna LE, Chandrasekaran V, Kumaran PP, Nutman TB, Babu S. Parasite-antigen driven expansion of IL-5(-) and IL-5(+) Th2 human subpopulations in lymphatic filariasis and their differential dependence on IL-10 and TGFβ. PLoS Negl Trop Dis Jan 30;8(1):e Parandhaman DK, Hanna LE, Narayanan S. PknE, a serine/threonine protein kinase of Mycobacterium tuberculosis initiates survival crosstalk that also impacts HIV coinfection. PLoS One Jan 8;9(1):e Hanna LE, Neogi U, Ranga U, Swaminathan S, Prasad VR. Phylogenetic Characterization of Six Full-Length HIV-1 Subtype C Molecular Clones from Three Patients: Identification of Rare Subtype C Strains Containing Two NF-κB Motifs in the Long Terminal Repeat. AIDS Res Hum Retroviruses Jun;30(6): Anuradha R, George PJ, Hanna LE, Chandrasekaran V, Kumaran P, Nutman TB, Babu S. IL- 4-, TGF-β-, and IL-1-dependent expansion of parasite antigen-specific Th9 cells is associated with clinical pathology in human lymphatic filariasis. J Immunol Sep 1;191(5): Selvaraj A, Pilakka-Kanthikeel S, Bhavani PK, Hanna LE, Pahwa S, Swaminathan S. Defective dendritic cell response to Toll-like receptor 7/8 agonists in perinatally HIV-infected children. Pathog Dis Dec;69(3): Damodharan S, Gujar R, Pattabiraman S, Nesakumar M, Hanna LE, Vadakkuppattu RD, Usha R. Expression and immunological characterization of cardamom mosaic virus coat protein displaying HIV gp41 epitopes. Microbiol Immunol May;57(5): Kumar NP, Gopinath V, Sridhar R, Hanna LE, Banurekha VV, Jawahar MS, Nutman TB, Babu S. IL-10 dependent suppression of type 1, type 2 and type 17 cytokines in active pulmonary tuberculosis. PLoS One. 2013;8(3):e Sundaramurthi JC, Ramanathan VD, Hanna LE. HLA-B*27:05-specific cytotoxic T lymphocyte epitopes in Indian HIV type 1C. AIDS Res Hum Retroviruses Jan;29(1): Sundaramurthi JC, Swaminathan S and Hanna LE. Resistance-associated epitopes of HIV-1C highly probable candidates for a multi-epitope vaccine. Immunogenetics 2012 Oct; 64(10): Hassan S, Debnath A, Mahalingam V and Hanna LE. Computational structural analysis of proteins of Mycobacterium tuberculosis and a resource for identifying off-targets. J Mol Model, 2012 Aug; 18(8): Sundaramurthi JC, Brindha S, Shobitha SR, Swathi A, Ramanandan P and Hanna LE. In silico identification of potential antigenic proteins and promiscuous CTL epitopes in Mycobacterium tuberculosis. Infect Genet Evol, 2012, 12(6): Jagadish C Sundaramurthi1 and Luke Elizabeth Hanna. HLA-A*0201-specific epitopes of Indian HIV-1C as candidates for vaccine design. BMC Infectious Diseases (2012) 12(Suppl 1):O15.

5 Complete List of Published Work in My Bibliography: Link to My Bibliography maintained by the US NLM: D. Research Support Ongoing Research Support: BIC/12(13)/2013 (ICMR Task Force) 04/ /2018 ICMR-Biomedical Informatics Centers, Second Phase The major goals include capture of valuable clinical/biomedical data generated by the medical professionals, initiate and support Genome-Wide Association Studies using high-throughput technologies for identification of disease-associated loci in Indian population, introduce latest technological advances for developing solutions for controlling pathogens causing diseases of national interest such as tuberculosis, malaria, AIDS, etc, and support large-scale collaborative projects through task-forces on modern biology such as metabolomics, metagenomics and systems modeling. NIH-CRDF Funding 03/ /2018 Establishment of an in-country PBMC EQAS Program. NIH Grant No. 1R21AI Role of Myeloid Derived Suppressor Cells in Mycobacterium tuberculosis reactivation in HIV- Mtb co infected individuals. This study will explore the role of a newly identified subset of monocytes called myeloid derived suppressor cells in reactivation of tuberculosis in HIV and tuberculosis co-infected individuals. CRDF Global Funding (through NIH/NIAID) Biomarkers for Tuberculosis Diagnosis and Treatment Response. The study involves identification of cellular biomarkers for predicting TB disease progression and treatment response. 4481/ART/AIDS/A-6/2009 (NACO) 10/2009 onwards Early diagnosis of HIV infection in children The goal of this project is to test all children born to HIV-infected women to identify the HIV-infected child early, prior to the development of clinical disease during the first months of life so as to start them on life-saving antiretroviral therapy. BT/PR12195/MED/15/118/2014 (DBT, GOI) 12/ /2017 Establishment of National TB Biorepository for RePORT India study. Completed Research Support (Last 5 years): USAID GRANT NO (IAVI through USAID) 01/ /2016 Analysis of protective humoral and cell mediated immunity in HIV vaccinated individuals

6 The study involves detailed profiling of the immunogenicity of a HIV-1 subtype C vaccine tested in a prime boost regimen in a Phase I trial at NIRT previously by characterization of HIV-specific humoral and cell mediated immune responses elicited in vaccinated individuals. BT/PR4847/MED/29/376/2012 (DBT-ICMR, GOI) 04/ /2016 Structure-based rational design and synthesis of inhibitors for various enzymes of HIV The goal of this research is target-based design, synthesis and evaluation of inhibitors for HIV enzymes like Reverse transcriptase and Integrase. 1R03AI (NIH-R03) 11/ /2013 Attenuated HIV/TB Vaccine for India The major goal of this project was to test whether a safe ramtb-hiv -1 subtype C prime and rmva- HIVC boost vaccination strategy engenders long lasting central memory responses after neonatal immunization. Estt/BMI/TRC (ICMR Task Force) 04/ /2012 ICMR-Biomedical Informatics Centers, First Phase The goals of this project included the establishment of a state of the art bioinformatics facility at the host institute to enhance ongoing research in the field of tuberculosis and HIV/AIDS using computational approaches and to impart skills in bioinformatics to medical and biomedical researchers within the state.

BIO DATA OF THE INVESTIGATOR(S) 1. Name (Dr./Kum./Smt./Shri) : Sujatha Narayanan First Name(s) Surname. 6. Discipline : Immunology & Molecular Biology

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