Academic Qualifications

Ph.D. (2009) – Dept. of Biochemistry, Indian Institute of Science, Bangalore.

M.Sc. Medical Biochemistry (2003) – JIPMER, Pondicherry University.

B.Sc. Biochemistry (2000) – Sri Sankara Arts and Science College, Madras University.

Professional Experience

Scientist-D (Nov 2015 Onwards) – Institute of Life Sciences, Bhubaneswar, India.

Ramanujan Fellow (Nov 2010 – Oct 2015) – Centre for Infectious Disease Research & Department of Biochemistry, IISc, Bangalore, India.

Postdoctoral Research Fellow (Jan 2010 – Sep 2010) – School of Biological Sciences, Nanyang Technological University, Singapore.

Research Associate (Sep 2009 – Dec 2009) – School of Biological Sciences, Nanyang Technological University, Singapore.

Research Interest

Malaria remains as one among the top five infectious diseases in the world leading to enormous morbidity and mortality. This devastating disease caused by Plasmodium species of phylum apicomplexa is transmitted by the bites of female Anopheles mosquitoes. The absence of an effective vaccine together with widespread and emerging resistance against frontline antimalarials including the most promising arteminsinin-based combination therapies has made malaria eradication daunting. For the past several decades, the malaria research has been focused mainly on asexual (blood) stages which are directly associated with disease pathogenesis, and the molecular aspects related to the transmission stages remained a black box.

Recently, it has been realized that besides targeting the blood stages, effective transmission blocking strategies are key for malaria eradication and this has been included as one of the prime agenda in WHO portfolio for malaria eradication. My research interest is mainly focused on gaining insights into the fascinating biology of Plasmodium transmission stages, and understanding the molecular and biochemical aspects that are crucial for the development of sexual stages in mosquitoes and liver stages in vertebrate hosts. Delineating these aspects and designing strategies to interfere with the homeostasis of host-parasite networks can be explored for new therapeutic approaches to prevent malaria transmission. I am also collaborating with industries to develop novel high-sensitive platforms for malaria diagnosis.

Awards & Honors

Received NAVDB Award for Outstanding Contribution on Molecular Biology from National Academy of Vector Borne Diseases, February 2017.

Global Health Travel Award funded by the Bill and Melinda Gates Foundation to attend Keystone Symposia on “The Science of Malaria Eradication” held at Mexico in February, 2014.

Awarded Ramanujan Fellowship for the year 2010 by Department of Science & Technology, Govt. of India.

Prof. Giri Memorial Medal, Institute of science, Bangalore for the Best Ph.D. Thesis of the year 2009-2010, Dept. of Biochemistry, Indian Institute of science, Bangalore.

Dr. A. S. Perumal Award, Indian Institute of science, Bangalore for the Best Performance in Research Training Program, Dept. of Biochemistry, Indian Institute of science, Bangalore.

Sathya Bhama Award, JIPMER, Pondicherry University for the Best Outgoing Student (2003).

Best Outgoing Student Award (2000), Sri Sankara Arts and Science College, Madras University

Other Recognitions

Reviewer for BIRAC’s Biotechnology Ignition Grant (BIG) scheme

Invited Reviewer for Nature Scientific Reports, Journal of Bacteriology & Parasitology, Molecular Biotechnology, Experimental Parasitology & Infection and Immunity

Member of Doctoral Advisory Committee, Manipal University (2013-2015)

MEDIA Coverage

1) “Indigenous malaria vaccine shows promise in mice studies”, S&T, The Hindu, April 17, 2014. http://www.thehindu.com/sci-tech/health/medicine-and-research/indigenous-malaria-vaccine-shows-promise-in-mice-studies/article5918997.ece

2) “Knocking down the malaria causing parasite”, S&T, The Hindu, August 22, 2013. http://www.thehindu.com/sci-tech/health/knocking-down-the-malaria-causing-parasite/article5045356.ece

3) Malaria Parasite-synthesized Heme is Essential in the Mosquito and Liver Stages and Complements Host Heme in the Blood Stages of Infection. Recommended in F1000 Microbiology for new finding and novel drug target. http://f1000.com/prime/718071268

Industrial Collaborations

Jigsaw Biosolutions Pvt Ltd, Bangalore to develop a novel PCR kit for Malaria detection based on unique IMR sequences in the parasite genome.

Omix Research & Diagnostic Laboratories Pvt Ltd, Bangalore to develop a novel Malaria point-of-care diagnostic test

Research Description

Parasitism relies on the successful exploitation of host cell resources through a wide range of crosstalk accomplished between host and parasite metabolic networks. Given the complexity of Plasmodium life cycle that alternates between vertebrate (human) and invertebrate (mosquito) hosts, the ease with which the malaria parasite contends different host environments remain astounding. While many studies have revealed these aspects in the asexual stages residing in human RBCs, the host-parasite interactions in the sexual and liver stages are yet to be explored in detail. Interestingly, the host niches of sexual and liver stages differ significantly from metabolically inert RBCs circulating in nutrient-rich plasma. Also, the molecular events underlying the parasite development and differentiation in the mosquito and liver stages are poorly understood.

Our laboratory is interested in understanding the molecular events that are involved in the sexual and liver stage development of Plasmodium using P. falciparum (human malaria parasite) as an in vitro model and P. berghei (rodent malaria parasite) as an in vivo model to study the entire life cycle of malaria parasite. We combine genetic, biochemical and molecular biological approaches to decipher the significance of metabolic pathways and metabolic adaptability of Plasmodium in the sexual and liver stages thereby, identifying the limiting metabolites and nutrients that become essential for the survival of parasite.

Our studies on heme and amino acid pathways of malaria parasite have revealed the existence of unique requirements in the sexual and liver stages that are critical for parasite development and therefore, disease transmission. Further, PbALAS (first enzyme in heme-biosynthetic pathway) knockout sporozoites could be explored as a potential genetically-attenuated vaccine candidate for liver stages in mouse model. Also, we are trying to understand the physiological relevance of transporters in the malaria parasite. To summarize, understanding host-parasite interactions at the level of nutritional requirements together with the transport mechanisms that are involved in the host-parasite interplay would help to identify the essential components required for parasite survival and give insights into basic parasite biology. The depletion of these essential components and prevention of their uptake would provide novel intervention strategies and new targets to interfere with disease progression and transmission. Of late, we have also started examining the molecular re-programming events occurring in Plasmodium that are responsible for disease virulence.

PUBLICATIONS

1) Raju, L.S., Kamath, S., Shetty, M.C., Satpathi, S., Mohanty, A.K., Ghosh, S.K., Kolluri, N., Klapperich, C.M., Cabodi, M., Padmanaban, G. and Nagaraj, V.A. (2019). Genome Mining-Based Identification of Identical Multi-Repeat Sequences (IMRS) in Plasmodium falciparum Genome for Highly Sensitive qPCR Assay and its Application in Malaria Diagnosis. J. Mol. Diagn. doi: 10.1016/j.jmoldx.2019.04.004.

2) Dende, C., Meena, J., Nagarajan, P., Nagaraj, V.A., Panda, A.K. and Padmanaban, G. (2017). Nanocurcumin is superior to native curcumin in preventing degenerative changes in Experimental Cerebral Malaria. Sci. Rep. 7(1):10062. doi: 10.1038/s41598-017-10672-9.

3) Nagaraj, V.A. and Padmanaban, G. (2017). Insights on heme synthesis in malaria parasite. Trends in Parasitol. 33, 583-586.

4) Padmanaban, G. and Nagaraj, V.A. (2017). Curcumin May Defy Medicinal Chemists. ACS Med. Chem. Lett. 8, 274.

5) Nagaraj, V.A., Mukhi, D., Sathishkumar, V., Subramani, P.A., Ghosh, S.K., Pandey, R.R., Shetty, M.C. and Padmanaban, G. (2015). Asparagine requirement in Plasmodium berghei as a target to prevent malaria transmission and liver infections. Nat. Commun. 6:8775. doi: 10.1038/ncomms9775.

6) Varadarajan, N.M., Sundaram, B., Subramani, P.A., Kalappa, D.M., Ghosh, S.K. and Nagaraj, V.A. (2014). Plasmodium berghei glycine cleavage system T-protein is non-essential for parasite survival in vertebrate and invertebrate hosts. Mol Biochem Parasitol. 197, 50-55.

7) Sundaram, B., Varadarajan, N.M., Subramani, P.A., Ghosh, S.K. and Nagaraj, V.A. (2014). Purification of a recombinant histidine-tagged lactate dehydrogenase from the malaria parasite, Plasmodium vivax, and characterization of its properties. Biotechnol Lett. 36, 2473-2480.

8) Nagaraj, V.A., Sundaram, B., Varadarajan, N.M., Subramani, P.A., Kalappa, D.M., Ghosh, S.K. and Padmanaban G. (2013). Malaria Parasite-synthesized Heme is Essential in the Mosquito and Liver Stages and Complements Host Heme in the Blood Stages of Infection. PLoS Pathogens 9(8):e1003522. doi: 10.1371/journal.ppat.1003522.

Recommended in F1000 Microbiology for new finding and novel drug target.

This work was also covered in the following newspaper articles.

“Knocking down the malaria causing parasite”, S&T, The Hindu, August 22, 2013. http://www.thehindu.com/sci-tech/health/knocking-down-the-malaria-causing-parasite/article5045356.ece

“Indigenous malaria vaccine shows promise in mice studies”, S&T, The Hindu, April 17, 2014. http://www.thehindu.com/sci-tech/health/medicine-and-research/indigenous-malaria-vaccine-shows-promise-in-mice-studies/article5918997.ece

9) Padmanaban, G., Nagaraj, V.A. and Rangarajan, P.N. (2012). Artemisinin-based combination with curcumin adds a new dimension to malaria therapy. Curr. Sci. 102, 704-711.

10) Vathsala, P.G., Dende, C., Nagaraj, V.A., Bhattacharya, D., Das, G., Rangarajan, P.N. and Padmanaban, G. (2012). Curcumin-arteether combination therapy of Plasmodium berghei-infected mice prevents recrudescence through immunomodulation. PLoS One. 7, e29442.

11) Nagaraj, V.A., Arumugam, R., Prasad, D., Rangarajan, P.N. and Padmanaban, G. (2010) Protoporphyrinogen IX oxidase from Plasmodium falciparum is anaerobic and is localized to the mitochondrion. Mol. Biochem. Parasitol. 174, 44-52.

12) Nagaraj, V.A., Prasad, D., Arumugam, R., Rangarajan, P.N. and Padmanaban, G. (2010). Characterization of coproporphyrinogen III oxidase in Plasmodium falciparum cytosol. Parasitol Int. 59, 121-127.

13) Nagaraj, V.A., Prasad, D., Rangarajan, P.N. and Padmanaban, G. (2009). Mitochondrial localization of functional ferrochelatase from Plasmodium falciparum. Mol. Biochem. Parasitol. 168, 109-112.

14) Nagaraj, V.A., Arumugam, R., Chandra, N.R., Prasad, D., Rangarajan, P.N. and Padmanaban, G. (2009). Localization of Plasmodium falciparum uroporphyrinogen III decarboxylase of the heme-biosynthetic pathway in the apicoplast and characterization of its catalytic properties. Int. J. Parasitol. 39, 559-568.

15) Nagaraj, V.A., Arumugam, R., Gopalakrishnan, B., Jyothsna, Y.S., Rangarajan, P.N. and Padmanaban, G. (2008). Unique properties of parasite genome-coded porphobilinogen deaminase from Plasmodium falciparum. J. Biol. Chem. 283, 437-444.

16) Padmanaban, G., Nagaraj, V.A. and Rangarajan, P.N. (2007). An alternative model for heme synthesis in the malarial parasite. Trends Biochem. Sci. 32, 443-449.

17) Padmanaban, G., Nagaraj, V.A. and Rangarajan, P.N. (2007). Drugs and drug targets against malaria. Curr. Sci. 92, 1545-1555.

18) Nandakumar, D.N., Nagaraj, V.A., Vathsala, P.G., Rangarajan, P.N. and Padmanaban, G. (2006). Curcumin – Artemisinin combination therapy for malaria. Antimicrob. Agents Chemother. 50, 1859-1860.

BOOK CHAPTERS

1) Padmanaban, G. and Nagaraj, V.A. (2017). Curcumin from turmeric as an adjunct drug? In: Studies in Natural Products Chemistry, Bioactive Natural Products. Edited by Atta-ur-Rahman. Volume 57, 2018, Pages 179-202.

2) Nagaraj, V.A., Rangarajan, P.N. and Padmanaban, G. (2014). Porphyrin Metabolism. Encyclopedia of Malaria. Springer, Edited by Hommel, M. and Kremsner. P.G. 1-11.

3) Padmanaban, G., Nagaraj, V.A. and Rangarajan, P.N. (2013). Unique Features of heme biosynthesis in the malaria parasite. Handbook of Porphyrin Science. With Applications to Chemistry, Physics, Materials Science, Engineering, Biology and Medicine. World Scientific Publishers, Edited by Kadish, K.M., Smith, K.M., Guilard,  R. and Ferreira, G.C. 27, 168-205.

LIST OF PATENTS GRANTED/FILED:

1) Indian Patent Application No. 1612/CHE/2005 (7.11.2005). A combination antimalarial drug therapy with curcumin and artemisinin. Nandakumar, D.N., Nagaraj. V.A., Vathsala, P.G., Rangarajan, P.N. and Padmanaban, G.

2) U.S. Patent No.  US 7,776,911 B2 dtd. August 17, 2010. Antimalarial Drug Containing Synergistic Combination of Curcumin and Artemisinin, Padmanaban, G., Bangalore (IN), Rangarajan, P.N., Bangalore, (IN), Vathsala, P. G. Bangalore, (IN), Nagaraj, V.A. Bangalore, (IN) and Nandakumar, D.N. Bangalore, (IN).

3) Nucleotide sequence, A method and kit thereof. Srinivasa R.L., Shwetha, K.U., Nagaraj, V.A. and Raji, M. Indian Patent Application no: 893/CHE/2013.

Aditya Anand

DST-Inspire Fellow

Sourav Ghosh

Junior Research Fellow

Chandana Shetty

Junior Research Fellow

P.M. Vaishalli

Junior Research Fellow

Subhashree Beura

Lab Technician

Research Grants

1) Amino acid requirements in the sexual and liver stages of malaria parasite – An immutable and versatile target for malaria transmission. DST-SERB. 2017-2020 (Principal Investigator)

2) Malaria Parasite Biology – An Avenue to Discover New Drug Targets. DBT. 2016-2020. (Principal Investigator for ILS; In collaboration with Indian Institute of Science, Bangalore & Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore)

2) An Innovative Algorithm-Based Detection of  Identical Multi-Repeat Sequences (IMRS) in the Genome of Plasmodium and its Validation in Malaria Diagnostics. BIRAC. 2014-2016. (In collaboration with Jigsaw Biosolutions, Bangalore)

3) Exploring the New Facets of Plasmodium Biology to Identify Potential Drug Targets. DST Ramanujan Fellowship. 2010-2015.

4) Generation of Prototype Lateral Flow Assay Kit using Antigen Specific Hybridomas to Develop Rapid Diagnostic Test for Clinical Diagnosis of Malaria. DBT-SBIRI. 2012-2015. (In collaboration with Indian Immunologicals, Hyderabad)

5) Deciphering the Functional Significance of Rab-mediated Vesicular Trafficking Processes in Malaria Parasite. DST-FAST TRACK. 2012-2015.

Also, there is Intramural Support from ILS.

At present, our laboratory is looking for enthusiastic Post-doctoral fellows and Junior Research Fellows who are willing to work on the fascinating biology of malaria parasite and make a significant contribution towards understanding the developmental aspects of Plasmodium transmission stages, transmission biology, disease virulence etc. For Post-doctoral positions, those who are having fellowships may email their resume to arun@ils.res.in.  Candidates willing to apply for post-doctoral fellowships of various funding agencies may also email their research interest on Plasmodium biology. Preference will be given to those who are having immunology/molecular parasitology/vector biology background. For JRF positions, candidates can look at ILS website for advertisements related to current openings.