My interests revolve around the genetics and biology of type III interferons (IFN). Type III IFNs, also known as IFN-lambda (IFNL or IFN-λ), are a recently discovered family of IFNs that are thought to be critical players at the host-environment interface involving the epithelial surfaces. In humans, they are even more interesting because certain genetic polymorphisms determine their expression and also show strong evidence of selection. I am interested to understand the association and the molecular mechanism behind the association of these polymorphisms with various infectious and inflammatory diseases affecting humans. I use genetic, epidemiological, molecular, and biochemical approaches in my work and draw inferences from suitable model systems.
De M, Sukla S, Bharatiya S, Keshri S, Roy DG, Roy S, Dutta D, Saha S, Ejazi SA, Ravichandiran V, Ali N, Chatterjee M, Chinnaswamy S. IFN-λ3 is induced by Leishmania donovani and can inhibit parasite growth in cell line models but not in the mouse model while it shows significant association with leishmaniasis in humans. Infect Immun. 2024 Jan 9:e0050423. doi: 10.1128/iai.00504-23. Epub ahead of print. PMID: 38193711.
Monocytes differentiated into macrophages and dendritic
cells in the presence of human IFN-λ3 or IFN-λ4 show distinct phenotypes. De M,
Bhushan A, Chinnaswamy S. J Leukoc Biol. 2020 Nov 17. doi:
10.1002/JLB.3A0120-001RRR. Online ahead of print. PMID: 33205487
SARS-CoV-2 infection in India bucks the trend: Trained innate immunity? Chinnaswamy S. Am J Hum Biol. 2020 Sep 23:e23504. doi: 10.1002/ajhb.23504. Online ahead of print. PMID: 32965717
Identifying causal variants at the interferon lambda locus in case-control studies: Utilizing non-synonymous variant rs117648444 to probe the role of IFN-λ4. Bhushan A, Chinnaswamy S. Gene. 2018 Jul 20;664:168-180. doi: 10.1016/j.gene.2018.04.076. Epub 2018 Apr 27. PMID: 29705128
The type III Interferon (IFN) locus also called as IFN-lambda (IFNL or IFN-λ) locus has four genes (IFNL1,2, 3 and 4) on human chromosome 19. IFNL1, 2 and 3 were discovered in 2003 (they were initially referred to as interleukins (IL) - IL29, IL28A and IL28B respectively) while IFNL4 (IFN-λ4) was only discovered in 2013. The expression of IFN-λ4 is genetically controlled; only those individuals carrying a ΔG allele but not a TT allele at rs368234815 (now merged into rs11322783) can express 179 amino acids containing protein with full antiviral activity. The ΔG allele frequency varies widely with ethnicity and geography, with maximal frequency seen in the African population. Even though IFN-λ4 was discovered in the context of hepatitis C virus (HCV) infections, it may have relevance in several infectious and inflammatory diseases of humans. This project has the objective of deciphering the functions of IFN-λ4 beyond its role as an antiviral cytokine and its significance in human health and disease. With an expected ΔG allele frequency of 0.35 or more, the Indian population has significant number of individuals that carry the potential to express IFN-λ4 and it is pertinent to study this novel cytokine especially in the context of increasing incidence of viral infections and the already prevalent inflammatory diseases in the country.
Under a Wellcome Trust/DBT India Alliance funded project I seek to answer the broader question: What is the function of IFN-λ4 in human health and disease. In this project I am interested to better define the functions of IFN-λ4 as an immunomodulatory cytokine, and seek to answer the questions: what other cellular proteins it interacts with? How does the potential to express a functional IFN-λ4 affect the basal antiviral states in healthy individuals? What is the molecular mechanism behind the association of the functional IFN-λ4-generating polymorphism with some of the common inflammatory diseases like asthma, COPD? Does IFN-λ4 genetically associate with common viral infections like dengue and COVID-19?
In another project (intramurally funded) I am interested to know the relationship between type III IFNs and an important intracellular protozoan parasite Leishmania donovani.
Current Projects (as PI):
1) Title: Functional interrogation of interferon lambda 4 (IFN-L4) in human health and disease; Funding Agency: DBT-Wellcome Trust India Alliance; Duration: 2018- 2022
2) Title: Characterization of lambda interferons in Leishmania infection; Funding Agency: NIBMG intramural; Duration: 2019-current.
| Year | Degree | University |
|---|---|---|
| 2010 | Ph.D | Texas A&M University at College Station, TX, USA |
| 2005 | MS | New Mexico State University at Las Cruces, NM, USA |
| 2003 | MVSc | Indian Veterinary Research Institute, UP, India |
| 1999 | BVSc&AH | Veterinary College, Bangalore, Karnataka, India |
Intermediate Fellow; DBT-Wellcome India Alliance; 2017
Visiting Scientist; Healthy Ageing Research Centre, Dept. of Immunology, Rheumatology and Allergy, Medical University of Lodz, Poland; 2015
Visiting Fellow; Jawaharlal Nehru Canter for Advanced Scientific Research, 2012
Member, Infectious Disease Biology Task Force; DBT, Govt. of India; 2014
2018
Dean’s List; New Mexico State University, Las Cruces, NM, USA; 2005
Junior Research Fellowship; ICAR for pursuing MVSc degree; 2000
Calcutta Consortium for Human Genetics
Indian Society of Human Genetics
Soceity of Leukocyte Biology
1) December 3, 2010: “Chronic Viral Hepatitis Research in India – Status and Future directions” a workshop conducted by the Liver Foundation of West Bengal at School of Digestive and Liver Diseases, IPGME&R, Kolkata. Title of talk: HCV and Innate Immunity.
2) December 3, 2010: 3rd Kolkata Liver meeting organized by the Liver Foundation of West Bengal at Vivekananda Institute of Medical Sciences, Kolkata.
3) II Healthy Ageing Research Centre conference on translational research on healthy ageing, 2016, Lodz, Poland (Plenary talk)
4) Transcription assembly meeting Bose Institute, Kolkata; 8th Novemeber 2016.
5) Second annual meeting of veterinary biochemists and biotechnologists of India, veterinary college, Bengaluru 2nd-3rd June 2017.
6) Mahatma Gandhi University, Kottayam, Kerala at the Euro-India International Conference on Experimental and Clinical Medicine (ICECM-2017), 10th Nov 2017.
7) World Congress on Genetics Genomics and Personalized Medicine held on 15th Nov 2017, J. N. Tata Auditorium, Indian Institute of Science, Bangalore.
8) 86th Annual Conference of Society of Biological Chemists (India), held at Jawaharlal Nehru University, Delhi, India, on 17th November, 2017.
9) Plenary talk at 18th All India Congress of Cytology and Genetics & International Symposium on “Translating Genes and Genomes” jointly organized by CSIR-Indian Institute of Chemical Biology and Archana Sharma Foundation of Calcutta on the 31st January 2018.
10) 20th Transcription Assembly Meeting 2018 held at CDFD, Hyderabad from 25th-27th July 2018.
11) 24th of October 2018 at Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Maryland, USA.
12) Sri Ramachandra Institute of Higher Education and Research, Chennai on 3rd April 2019.
13) Recent Advances in Molecular Diagnostics Hands-on Workshop for Laboratory Medicine Practitioners at NIBMG, Kalyani; Date: December 17, 2019
14) Calcutta University for the ‘UGC-HRDC refresher course in Life Science’ on Jan 4th, 2020, Department of Botany, Ballygunge Science College Campus, Calcutta University, Kolkata.
15) “IFNL4 has immunomodulatory functions” at the IFNL zoom meeting to international IFNL community on 25th Jan 2021
16)"LEISHMANIA DONOVANI INFECTION INDUCES IFN-L3 IN CELLS, MICE, AND HUMANS" at the Interferon Lambda 2022, satellite hybrid meeting of the International Cytokine and Interferon Society held on 24-25th Sep 2022 at Hawaii, USA
1) Cloning, expression and characterization of antiviral activity of IFN-lambdas. DST-SERB; 05/2012-04/2015
2) Genetic and functional characterization of IL28B gene variation in chronic HCV patients from India. DBT; 10-2014-10-2017
3) A pilot study on genetic and functional analysis of Type III interferons in Asthma: understanding molecular pathology by an infection-associated inflammation perspective. NIBMG; 08/2015-08/2017
IFN-λ3 is induced
by Leishmania donovani and can inhibit parasite growth in cell
line models but not in the mouse model while it shows significant association
with leishmaniasis in humans. De M, Sukla S, Bharatiya S, Keshri S, Roy DG, Roy
S, Dutta D, Saha S, Ejazi SA, Ravichandiran V, Ali N, Chatterjee M, Chinnaswamy
S.
Gender-dependent
multiple cross-phenotype association of interferon lambda genetic variants with
peripheral blood profiles in healthy individuals. Roy DG, Singh L,
Chaturvedi HK, Chinnaswamy S. Mol Genet Genomic Med. 2024;12:e2292. PMID: 37795763.
A Novel
Inactive Isoform with a Restored Reading Frame Is Expressed from the Human
Interferon Lambda 4 TT Allele at rs368234815. Bharatiya S, Agarwal A, Chinnaswamy
S. J Interferon Cytokine Res. 2023;43(9):370–378; doi:
10.1089/jir.2022.0199. PMID: 36880961.
Distinct
molecular phenotypes involving several human diseases are induced by IFN-λ3 and
IFN-λ4 in monocyte-derived macrophages. De M, Bhushan A, Grubbe WS, Roy S,
Mendoza JL, Chinnaswamy S. 2022. Genes Immun. 23: 73–84 PMID: 35115664 PMID: 35115664.
Understanding
the devastating second wave of COVID-19 pandemic in India. Chinnaswamy S. American
Journal of Human Biology. 2021, 33(6). e23671. doi.org/10.1002/ajhb.23671,
PMID: 34469036
Functional
genetic variants of the IFN-λ3 (IL28B) gene and transcription factor
interactions on its promoter. Roy S, Roy DG, Bhushan A, Bharatiya
S, Chinnaswamy S. Cytokine, 2021, 142,
155491.PMID: 33725487
Monocytes
differentiated into macrophages and dendritic cells in the presence of human
IFN-λ3 or IFN-λ4 show distinct phenotypes. De M, Bhushan A, Chinnaswamy
S. J Leukoc Biol. 2021, 110(2): 357-374. PMID:
33205487
SARS-CoV-2
infection in India bucks the trend: Trained innate immunity? Chinnaswamy S. Am
J Hum Biol. 2021, 33(6). e23504. doi: 10.1002/ajhb.23504. PMID: 32965717
Mutations
in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for
the ongoing outbreak in India and impact on viral structure and host
susceptibility. Maitra A, Sarkar MC, Raheja H, Biswas NK, Chakraborti S,
Singh AK, Ghosh S, Sarkar S, Patra S, Mondal RK, Ghosh T, Chatterjee A, Banu H,
Majumdar A, Chinnaswamy S, Srinivasan N, Dutta S, DAS S. J Biosci. 2020;45(1):76.
doi: 10.1007/s12038-020-00046-1. PMID: 32515358
The Genetic
Association of IFN-λs with Human Inflammatory Disorders Remains a
Conundrum. Chinnaswamy S, Kowalski ML. J Interferon Cytokine Res. 2019
Oct;39(10):594-598. doi: 10.1089/jir.2019.0009. Epub 2019 Jun 4. PMID: 31161954
Identifying
causal variants at the interferon lambda locus in case-control studies:
Utilizing non-synonymous variant rs117648444 to probe the role of
IFN-λ4. Bhushan A, Chinnaswamy S. Gene. 2018 Jul
20;664:168-180. doi: 10.1016/j.gene.2018.04.076. Epub 2018 Apr 27 PMID:
29705128
A
functional IFN-λ4-generating DNA polymorphism could protect older asthmatic
women from aeroallergen sensitization and associate with clinical features of
asthma. Chinnaswamy S, Wardzynska A, Pawelczyk M, Makowska J, Skaaby T,
Mercader JM, Ahluwalia TS, Grarup N, Guindo-Martinez M, Bisgaard H, Torrents D,
Linneberg A, Bønnelykke K, Kowalski ML. Sci Rep. 2017 Sep
5;7(1):10500. doi: 10.1038/s41598-017-10467-y. PMID: 28874741
Confounding
by Single Nucleotide Polymorphism rs117648444 (P70S) Affects the Association of
Interferon Lambda Locus Variants with Response to Interferon-α-Ribavirin
Therapy in Patients with Chronic Genotype 3 Hepatitis C Virus Infection.
Bhushan A, Ghosh S, Bhattacharjee S, Chinnaswamy S. J Interferon
Cytokine Res. 2017 Aug;37(8):369-382. doi: 10.1089/jir.2017.0002. Epub
2017 Jul 20. PMID: 28727946
Gene-disease
association with human IFNL locus polymorphisms extends beyond hepatitis C
virus infections. Chinnaswamy S. Genes Immun. 2016
Jul;17(5):265-75. doi: 10.1038/gene.2016.24. Epub 2016 Jun 9. PMID: 27278127
Roles for
Transcription Factors Sp1, NF-κB, IRF3, and IRF7 in Expression of the Human
IFNL4 Gene. Chinnaswamy S, Bhushan A, Behera AK, Ghosh S, Rampurkar V,
Chandra V, Pandit B, Kundu TK. Viral Immunol. 2016
Jan-Feb;29(1):49-63. doi: 10.1089/vim.2015.0076. Epub 2015 Dec 18. PMID:
26684959
Association
of IL28B single nucleotide polymorphism rs8099917 with response to treatment in
genotype 3 HCV-infected patients from India. Chinnaswamy S, Das K,
Bairagya BB, Bhattacharyya C, Shalimar, Duseja A, Amarapurkar D, Rosangluaia,
Chowdhury S, Konar A, Majumder PP, Chowdhury A. Trop Gastroenterol. 2014
Apr-Jun;35(2):96-102. doi: 10.7869/tg.187. PMID: 25470871
A single
nucleotide polymorphism associated with hepatitis C virus infections located in
the distal region of the IL28B promoter influences NF-κB-mediated gene
transcription. Chinnaswamy S, Chatterjee S, Boopathi R, Mukherjee S,
Bhattacharjee S, Kundu TK. PLoS One. 2013 Oct 8;8(10):e75495.
doi: 10.1371/journal.pone.0075495. eCollection 2013. PMID: 24116050
The
adenine-rich tract in the 5ʹ-end of the hepatitis C virus ORF encodes a peptide
regulating the binding of the C protein to RNA. Chinnaswamy S, Lott
WB. Acta Virol. 2012;56(3):217-26. doi:
10.4149/av_2012_03_217. PMID: 23043601
Assays for
RNA synthesis and replication by the hepatitis C virus Kao CC, Fan B, Chinnaswamy
S, Cai H, Ranjith-Kumar CT, Deval J Frontiers in Biology. 2012; 7
(3), 233-245.
Conformations
of the monomeric hepatitis C virus RNA-dependent RNA polymerase. Chinnaswamy
S#, Ayaluru M#, Yi G, Cai H, Palaninathan S and Kao CC. Virus
Adaptation And Treatment, 2010; 2:21-39. (#equal contributions).
An update
on the small molecule inhibitors of the HCV NS5B polymerase: effects on RNA
synthesis in vitro, on cultured cells and potential resistance in viral
quasispecies. Chinnaswamy S, Cai H and Kao CC. Virus Adaptation
And Treatment, 2010; 2:73-89.
Regulation
of de novo-initiated RNA synthesis in hepatitis C virus RNA-dependent RNA
polymerase by intermolecular interactions. Chinnaswamy S, Murali A, Li P,
Fujisaki K, Kao CC. J Virol. 2010 Jun;84(12):5923-35. doi:
10.1128/JVI.02446-09. Epub 2010 Apr 7. PMID: 20375156
Mutations
in the hepatitis C virus polymerase that increase RNA binding can confer
resistance to cyclosporine A.Liu Z, Robida JM, Chinnaswamy S, Yi G,
Robotham JM, Nelson HB, Irsigler A, Kao CC, Tang H. Hepatology. 2009
Jul;50(1):25-33. doi: 10.1002/hep.22987. PMID: 19489073
Impaired
replication of hepatitis C virus containing mutations in a conserved NS5B
retinoblastoma protein-binding motif. McGivern DR, Villanueva RA, Chinnaswamy
S, Kao CC, Lemon SM. J Virol. 2009 Aug;83(15):7422-33. doi:
10.1128/JVI.00262-09. Epub 2009 May 20.PMID: 19458004
A locking
mechanism regulates RNA synthesis and host protein interaction by the hepatitis
C virus polymerase. Chinnaswamy S, Yarbrough I, Palaninathan S, Kumar CT,
Vijayaraghavan V, Demeler B, Lemon SM, Sacchettini JC, Kao CC. J Biol
Chem. 2008 Jul 18;283(29):20535-46. doi: 10.1074/jbc.M801490200. Epub
2008 Apr 28. PMID: 18442978
Post-doctoral fellows:
Dr. Manjarika De PhD (Jadavpur University/IICB, Kolkata)
PhD students:
Seema Bharatiya,
Debarati Guha-Roy,
Integrated MS-PhD students:
Sagar Keshri,
Aditya Agarwal
