Qualification: 
Ph.D
lalithabiswas@aims.amrita.edu

Dr. Lalitha Biswas joined as Assistant Professor at Amrita Institute of Medical Sciences in Jan 2010. She obtained her Ph.D from the University of Tuebingen, Germany. Her postdoctoral training was at University of Tuebingen, Germany and Purdue University, Indiana, USA. She was a member of the Graduate College Infection Biology (GKI-685), German Research Foundation and Sonder Forshungs Bereich (SFB). A couple of research projects on which she is currently working on is concentrated on molecular biology and Infection biology which is funded by DST and ICMR.

She adds to her achievements the author and co - author of nearly 11 publications in various reputed journals like journal of immunology, journal of Bacteriology etc. She qualified CSIR - NET in the year 2000. Apart from these she owned the DFG fellowship from 2002 - 2006 and also received the fellowship from German Sonder Forshungs Bereich for the year 2007 - 2009.

Currently, Dr. Biswas also heads the Molecular biology diagnostic laboratory, which provides diagnostic services under various categories such as histocompatability & immunogenetics, gene testing, pharmacogenomics, cancer genetics and molecular basis of infectious diseases.

Publications

Publication Type: Journal Article

Year of Publication Title

2017

P. S. Panicker, Melge, A. R., Dr. Lalitha Biswas, Keechilat, P., and Mohan, C. G., “Epidermal Growth Factor Receptor (EGFR) Structure-based Bioactive Pharmacophore Models for Identifying Next-generation Inhibitors Against Clinically relevant EGFR Mutations”, Chemical Biology & Drug Design, vol. 90, pp. 629-636, 2017.[Abstract]


Present work elucidates identification of next generation inhibitors for clinically relevant mutations of epidermal growth factor receptor (EGFR) using structure-based bioactive pharmacophore modeling followed by virtual screening (VS) techniques. Three-dimensional (3D) pharmacophore models of EGFR and its different mutants were generated. This includes seven 3D pharmacophoric points with three different chemical features (descriptors), that is, one hydrogen bond donor, three hydrogen bond acceptors and three aromatic rings. Pharmacophore models were validated using decoy dataset, Receiver operating characteristic plot, and external dataset compounds. The robust, bioactive 3D e-pharmacophore models were then used for VS of four different small compound databases: FDA approved, investigational, anticancer, and bioactive compounds collections of Selleck Chemicals. CUDC101 a multitargeted kinase inhibitor showed highest binding free energy and 3D pharmacophore fit value than the well known EGFR inhibitors, Gefitinib and Erlotinib. Further, we obtained ML167 as the second best hit on VS from bioactive database showing high binding energy and pharmacophore fit value with respect to EGFR receptor and its mutants. Optimistically, presented drug discovery based on the computational study serves as a foundation in identifying and designing of more potent EGFR next-generation kinase inhibitors and warrants further experimental studies to fight against lung cancer.

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2017

Dr. Lalitha Biswas, CG, N., M, B., Pradeep Jacob, Riju R. Menon, AK, R., and K, N., “Lack of Association of B-type Raf Kinase V600E Mutation with High-risk Tumor Features and Adverse Outcome in Conventional and Follicular Variants of Papillary Thyroid Carcinoma”, Indian Journal of Endocrinol Metab, vol. 21, no. 2, pp. 329-333, 2017.[Abstract]


INTRODUCTION:
Somatic B-type Raf kinase (BRAF) V600E mutation in exon 15 was frequently found in high frequencies associated with papillary thyroid cancer (PTC). The phenotype of these cancers expressed aggressive clinical and pathological features. The present study aimed to assess the prevalence of BRAF V600E mutation among conventional and follicular variants of PTC and its association with aggressive tumor factors and outcome.

STUDY DESIGN:
Patients who were operated and received further treatment for PTC during 2012 were included in the study. BRAF V600E mutation analysis was done by extracting genomic DNA from tumor tissue.

RESULTS:
Of the 59 patients included in the study, 51% harbored BRAF V600E mutation, but the mutation status was not associated with aggressive tumor factors and adverse outcome.

CONCLUSION:
BRAF V600E mutation was not significant predictor of aggressive tumor behavior in conventional and follicular variants of PTC.

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2017

G. Baranwal, Mohammad, M., Jarneborn, A., Reddy, B. Raghunath, Golla, A., Chakravarty, S., Dr. Lalitha Biswas, Götz, F., Shankarappa, S., Jin, T., and Raja Biswas, “Impact of Cell Wall Peptidoglycan O-acetylation on the Pathogenesis of Staphylococcus Aureus in Septic Arthritis”, International Journal of Medical Microbiology, vol. 307, pp. 388 - 397, 2017.[Abstract]


Staphylococcus aureus (S. aureus) is one of the most common pathogen causing septic arthritis. To colonize the joints and establish septic arthritis this bacterium needs to resist the host innate immune responses. Lysozyme secreted by neutrophils and macrophages is an important defense protein present in the joint synovial fluids. S. aureus is known to be resistant to lysozyme due to its peptidoglycan modification by O-acetylation of N-acetyl muramic acid. In this study we have investigated the role of O-acetylated peptidoglycan in septic arthritis. Using mouse models for both local and hematogenous S. aureus arthritis we compared the onset and progress of the disease induced by O-acetyl transferase mutant and the parenteral wild type SA113 strain. The disease progression was assessed by observing the clinical parameters including body weight, arthritis, and functionality of the affected limbs. Further X-ray and histopathological examinations were performed to monitor the synovitis and bone damage. In local S. aureus arthritis model, mice inoculated with the ΔoatA strain developed milder disease (in terms of knee swelling, motor and movement functionality) compared to mice inoculated with the wild type SA113 strain. X-ray and histopathological data revealed that ΔoatA infected mice knee joints had significantly lesser joint destruction, which was accompanied by reduced bacterial load in knee joints. Similarly, in hematogenous S. aureus arthritis model, ΔoatA mutant strain induced significantly less severe clinical septic arthritis compared to its parental strain, which is in accordance with radiological findings. Our data indicate that peptidoglycan O-acetylation plays an important role in S. aureus mediated septic arthritis.

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2017

Dr. Lalitha Biswas, S, I., M, S., P, K., J, M., R, J., R, R., A, W., ,, SM, C. Mali, V, V., A, C., S, D., A, O., G, K., R, N., A, M., Z, P., and M, E., “First Two Bilateral Hand Transplantations in India (Part 4): Immediate Post-operative Care, Immunosuppression Protocol and Monitoring”, Indian J Plast Surg, vol. 50, no. 2, pp. 168-172, 2017.[Abstract]


Being able to counter immune-mediated rejection has for decades been the single largest obstacle for the progress of vascular composite allotransplantation (VCA). The human immune system performs the key role of differentiating the 'self ' from the 'non-self '. This, although is quintessential to eliminate or resist infections, also resists the acceptance of an allograft which it promptly recognises as 'non-self'.

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2016

C. S. Keechilot, Shenoy, V., Kumar, A., Dr. Lalitha Biswas, Vijayrajratnam, S., Dinesh, K., and Dr. Prem Kumar Nair, “Detection of Occult Hepatitis B and Window Period Infection Among Blood Donors by Individual donation Nucleic Acid Testing in a Tertiary Care Center in South India”, Pathogens and Global Health, pp. 1-5, 2016.[Abstract]


With the introduction of highly sensitive hepatitis B surface antigen immunoassay, transfusion associated HBV infection have reduced drastically but they still tend to occur due to blood donors with occult hepatitis B infection (OBI) and window period (WP) infection. Sera from, 24338 healthy voluntary blood donors were screened for HBsAg, HIV and HCV antibody using Vitros Enhanced Chemiluminescent Immunoassay. The median age of the donor population was 30 (range 18–54) with male preponderance (98%). All serologically negative samples were screened by nucleic acid testing (NAT) for viral DNA and RNA. NAT-positive samples were subjected to discriminatory NAT for HBV, HCV, and HIV and all samples positive for HBV DNA were tested for anti-HBc, anti-HBs, HBeAg. Viral load was determined using artus HBV RG PCR Kit. Of the 24,338 donors screened, 99.81% (24292/24338) were HBsAg negative of which NAT was positive for HBV DNA in 0.0205% (5/24292) donors. Four NAT positive donors had viral load of <200 IU/ml making them true cases of OBI. One NAT positive donor was negative for all antibodies making it a case of WP infection. Among OBI donors, 75% (3/4) were immune and all were negative for HBeAg. Precise HBV viral load could not be determined in all (5/5) NAT positive donors due to viral loads below the detection limit of the artus HBV RG PCR Kit. The overall incidence of OBI and WP infections was found to be low at 1 in 6503 and 1 in 24214 donations, respectively. More studies are needed to determine the actual burden of WP infections in Indian blood donors.

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2015

N. Nair, Vinod, V., Suresh, M. K., Vijayrajratnam, S., Dr. Lalitha Biswas, Peethambaran, R., Vasudevan, A. K., and Dr. Raja Biswas, “Amidase, a Cell Wall Hydrolase, Elicits Protective Immunity Against Staphylococcus Aureus and S. Epidermidis”, International Journal of Biological Macromolecules, vol. 77, pp. 314-321, 2015.[Abstract]


The morbidity and the mortality associated with Staphylococcus aureus and S. epidermidis infections have greatly increased due to the rapid emergence of highly virulent and antibiotic resistant strains. Development of a vaccine-based therapy is greatly desired. However, no staphylococcal vaccine is available till date. In this study, we have identified Major amidase (Atl-AM) as a prime candidate for future vaccine design against these pathogens. Atl-AM is a multi-functional non-covalently cell wall associated protein which is involved in staphylococcal cell separation after cell division, host extracellular matrix adhesion and biofilm formation. Atl-AM is present on the surface of diverse S. aureus and S. epidermidis strains. When used in combination with Freund's adjuvant, Atl-AM generated a mixed Th1 and Th2 mediated immune response which is skewed more toward Th1; and showed increased production of opsonophagocytic IgG2a and IgG2b antibodies. Significant protective immune response was observed when vaccinated mice were challenged with S. aureus or S. epidermidis. Vaccination prevented the systemic dissemination of both organisms. Our results demonstrate the remarkable efficacy of Atl-AM as a vaccine candidate against both of these pathogens. © 2015 Elsevier B.V.

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2014

N. Nair, Biswas, R., Götz, F., and Dr. Lalitha Biswas, “Impact of Staphylococcus aureus on Pathogenesis in Polymicrobial Infections”, Infection and Immunity, vol. 82, pp. 2162–2169, 2014.[Abstract]


Polymicrobial infections involving Staphylococcus aureus exhibit enhanced disease severity and morbidity. We reviewed the nature of polymicrobial interactions between S. aureus and other bacterial, fungal, and viral cocolonizers. Microbes that were frequently recovered from the infection site with S. aureus are Haemophilus influenzae, Enterococcus faecalis, Pseudomonas aeruginosa, Streptococcus pneumoniae, Corynebacterium sp., Lactobacillus sp., Candida albicans, and influenza virus. Detailed analyses of several in vitro and in vivo observations demonstrate that S. aureus exhibits cooperative relations with C. albicans, E. faecalis, H. influenzae, and influenza virus and competitive relations with P. aeruginosa, Streptococcus pneumoniae, Lactobacillus sp., and Corynebacterium sp. Interactions of both types influence changes in S. aureus that alter its characteristics in terms of colony formation, protein expression, pathogenicity, and antibiotic susceptibility.

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2014

A. Kumar, Sreehari, S., Velayudhan, K., Dr. Lalitha Biswas, Babu, R., Ahmed, S., Sharma, N., Kurupath, V. P., Jojo, A., Dinesh, K. R., Karim, S., and Biswas, R., “Autochthonous Blastomycosis of the Adrenal: First Case Report from Asia”, The American Journal of Tropical Medicine and Hygiene, vol. 90, 2014.

2013

Va Sukhithasri, Nisha, Na, Dr. Lalitha Biswas, Kumar, VbAnil, and Dr. Raja Biswas, “Innate immune recognition of microbial cell wall components and microbial strategies to evade such recognitions”, Microbiological Research, vol. 168, pp. 396-406, 2013.[Abstract]


The innate immune system constitutes the first line of defence against invading microbes. The basis of this defence resides in the recognition of defined structural motifs of the microbes called "Microbial associated molecular patterns" that are absent in the host. Cell wall, the outer layer of both bacterial and fungal cells, a unique structure that is absent in the host and is recognized by the germ line encoded host receptors. Nucleotide oligomerization domain proteins, peptidoglycan recognition proteins and C-type lectins are host receptors that are involved in the recognition of bacterial cell wall (usually called peptidoglycan), whereas fungal cell wall components (N- and O-linked mannans, β-glucans etc.) are recognized by host receptors like C-type lectins (Dectin-1, Dectin-2, mannose receptor, DC-SIGN), Toll like receptors-2 and -4 (TLR-2 and TLR-4). These recognitions lead to activation of a variety of host signaling cascades and ultimate production of anti-microbial compounds including phospholipase A2, antimicrobial peptides, lysozyme, reactive oxygen and nitrogen species. These molecules act in cohort against the invading microbes to eradicate infections. Additionally pathogen recognition leads to the production of cytokines, which further activate the adaptive immune system. Both pathogenic and commensal bacteria and fungus use numerous strategies to subvert the host defence. These strategies include bacterial peptidoglycan glycan backbone modifications by O-acetylation, N-deacetylation, N-glycolylation and stem peptide modifications by amidation of meso-Diaminopimelic acid; fungal cell wall modifications by shielding the β-glucan layer with mannoproteins and α-1,3 glucan. This review focuses on the recent advances in understanding the role of bacterial and fungal cell wall in their innate immune recognition and evasion strategies. © 2013 Elsevier GmbH.

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