A plethora of genetic and environmental factors fundamentally define a complex disease. Concurrently, identification and precise measurement of such contributing factors are challenging because effect of a single factor might be masked or confounded by other factors. Nonetheless, the genetic dissection of complex diseases can immensely be aided by distinctions between gene identification and gene effect characterization. My research is focused on investigating genetic underpinnings in disorders with neuronal defects. Specifically, I have two broad objectives; a) complex traits associated visual neurodegeneration and b) genetic heterogeneity in rare diseases with neuronal defects. I use an integrative approach that includes high throughput omics analyses amalgamated with appropriate functional investigations in cell and zebrafish. I believe this would lead to a deterministic path of genomic medicine and therefore be beneficial to patients suffering from these diseases.
One of the major focus of my lab is investigating biological relevance of GWAS findings which essentially includes investigating genomic regulatory elements, allele specific genomic activity and activity of the regulatory elements. This would be complemented with functional validation in zebrafish, which includes confirming the functionality of genes and regulatory elements underlying disease biology across a variety of complex human traits involving visual neurodegeneration with high efficiency and generation of relevant zebrafish model that uphold in-depth studies of disease mechanisms. Another major focus includes understanding genetic heterogeneity in rare disease spectrum, where the approach is performing functional investigation of genomic signatures causal or acting as genetic modifiers in rare neurodegenerative disease spectrum that includes developmental glaucoma, congenital neuromuscular disorders and congenital deafness using RNA-guided nuclease and antisense oligo technologies in zebrafish model.
A few of my externally funded projects include genome-wide association study (GWAS) on extreme phenotypes of angle closure glaucoma, functional genomics of rare eye diseases primarily focused on developmental glaucoma spectrum and genomic architecture of non-syndromic hearing loss.
|2007||Ph.D||Indian Institute of Chemical Biology/Jadavpur University|
|2001||M.Sc||Banaras Hindu University|
|1999||B.Sc||University of Calcutta|
Selected as member of Indian National Young Academy of Science (INYAS), an initiative of Indian National Science Academy (INSA) for the period of 2017-2021
Travel award from Department of Science & Technology, Govt. of India to attend the annual meeting of the Association of Research in Vision and Ophthalmology (ARVO) at Denver, USA
Travel award from Team to Prevent Blindness at the University of Alberta to attend the Translational Glaucoma Meeting.
Young Investigator platform presentation and Travel award from the International Society of Eye Research (ISER) .
Travel award from the Association of Research in Vision and Ophthalmology (ARVO)
|2009||Travel award from the organizers of Asia-ARVO 2009.|
1. Molecular Basis of Pathogenesis in Childhood Rare Eye Diseases (Co-Investigator, funded by Science & Engineering Research Board, DST, Govt. of India)
2. Towards understanding genetic architecture underlying hereditary non-syndromic hearing loss (NSHL), (Principal Investigator, funded by DBT, Govt. of India)
3. Investigating genomic signatures causal to rare congenital muscle disorders in Indian population. NIBMG intramural funding support to MA.
4. Functional annotation of CNTNAP5 variants in PACG (ICMR-SRF project of Mr. Sudipta Chakraborty, Supervisor: Dr. Moulinath Acharya)
1. Genome-wide association study of phenotypic extremes in primary angle closure glaucoma (Principal Investigator, funded by DBT, Govt. of India)
2. Disease-Phenotype Deconvolution in Genetic Eye Diseases Using OMIM Database
Post-Doctoral Researcher, Department of Biological Sciences and Centre for Prions and Protein Folding Diseases, University of Alberta, CANADA (March 2011-November 2011)
Area of research: Studying the mechanism of interaction between prion protein (PrP) and amyloid precursor protein (APP) from the perspective of their involvement in pathways leading to neuronal cell death.
Post-Doctoral Fellow, Department of Medical Genetics, University of Alberta, CANADA (May 2007-February 2011)
Area of research: A. Identification and characterization novel interacting protein/s for PITX2 transcription factor. B. Studying regulatory network of FOXC1 and PITX2 transcription factors involved in Axenfeld-Reiger syndrome and glaucoma.
PhD : Title of the Thesis: Molecular Characterization of Primary Open Angle Glaucoma in Indian Patients.
35. Identification of a shared, common haplotype segregating with an SGCB c.544 T > G mutation in Indian patients affected with sarcoglycanopathy. Sanga S, Chakraborty S, Bardhan M, Polavarapu K, Kumar PV, Bhattacharyya C, Nashi S, Vengalil S, Thenral SG, Ramprasad VL, Nalini A, Basu A, ACHARYA M*. (2023) Scientific Reports 13, 15095. https://doi.org/10.1038/s41598-023-41487-6
34. A quantitative trait GWAS on lens thickness identifies novel risk loci on PTPRM in the narrow angle individuals susceptible to PACG. Chakraborty S., Sharma A., Pal S, Sharma A, Sihota R, Bhattacharjee S., ACHARYA M*. (2023) European Journal of Ophthalmology Mar 17:11206721231160988. doi: 10.1177/11206721231160988
33. Large Region of Homozygous (ROH) Identified in Indian Patients with Autosomal Recessive Limb-Girdle Muscular Dystrophy with p.Thr182Pro Variant in SGCB Gene. Manjunath. V, Thenral SG, Lakshmi BR, Nalini A, Bassi A, Karthikeyan KP, Piyusha K, Menon R, Malhotra A, Praveena LS, Anjanappa RM, Murugan SMS, Kiran Polavarapu K, Bardhan M, Preethish-Kumar V, Vengalil S, Nashi S, Sanga S, ACHARYA M, Raju R, Pai VR, Ramprasad VL, Gupta R. (2023) Human Mutation vol 2023 | Article ID 4362273 | https://doi.org/10.1155/2023/4362273
32. NOTCH pathway inactivation reprograms stem-like oral cancer cells to JAK-STAT dependent state and provides the opportunity of synthetic lethality. Ghosh S, Mitra P, Saha U, Nandi R, Jena S, Ghosh A, Saha Roy S, ACHARYA M, Biswas NK, Singh S. (2023) Translational Oncology Apr 11;32:101669. doi: 10.1016/j.tranon.2023.101669
31. A photoactive lysosome targeting Ru II complex downregulates stemness genes in oral squamous cell carcinoma. Roy S, Mitra P, Acharya S, Saha Roy S, Ghosh S, Maji M, Modak, N, Ghosh N, ACHARYA M, Singh S, Mukherjee A (2022) Inorganic Chemistry Frontiers, 9, 5840–5852
30. Clinical, genetic profile and disease progression of sarcoglycanopathies in a large cohort from India: high prevalence of SGCB c.544A > C. Bardhan M, Anjanappa RM, Polavarapu K, Preethish‑Kumar V , Vengalil S, Nashi S, Sanga S, Padmanabh H, Valasani RK, Nishadham V, Keerthipriya M, Geetha TS, Ramprasad V, Arunachal G, Thomas PT, ACHARYA M, Nalini A (2022) Neurogenetics, Apr 13. doi: 10.1007/s10048-022-00690-9
29. Cytotoxic Ruthenium(II) Complexes of Pyrazolylbenzimidazole Ligands That Inhibit VEGFR2 Phosphorylation. Chakraborty A, Roy S, Chakraborty MP, Saha Roy S, Purkait K, Koley TS, Das R, ACHARYA M, Mukherjee A (2021) Inorg. Chem. December 6;60(23):18379-18394.
28. A genome-wide association study on individuals with occludable angles identifies potential risk loci for intraocular pressure. Chakraborty S., Sharma A., Bagchi I., Pal S., Bhattacharyya C., Gupta V., Maitra A., Bhattacharjee S., Sharma A, Sihota R, ACHARYA M* (2021) J. Genet. October 100, 69.
27. A Haplotype-based genomic analysis reveals novel association of CNTNAP5 genic region with primary angle-closure glaucoma. Chakraborty S, Sharma A, Sharma Ar, Sihota R, Bhattacharjee S, ACHARYA M* (2021) J. Biosci. February 2021 46:15
26. Role of PRKC Apoptosis WT1 Regulator in Ocular Development and Diseases. Ahmed T, Mallick TR, Walter MA and ACHARYA M* (2021), Book Title: Tumor Suppressor Par-4: Role in Cancer and Other Diseases, Springer. In press.
25. Whole Exome Analysis of Congenital Muscular Dystrophy and Congenital Myopathy Patients from India Reveal a Wide Spectrum of Known and Novel Mutations. Sanga S, Ghosh A, Kumar K, Polavarapu K, Kumar PV, Vengalil S, Nashi S, Bardhan M, Arunachal G, Raju S, Gayathri N, Biswas NK, Chakrabarti S, Nalini A, Roy S, ACHARYA M* (2020). Eur. J.Neurol., October 2020:00:1-12
24. A “CRISPR” Overview of genome editing: potentials and challenges. Chakraborty S, ACHARYA M* (2017) Sci.Cult. July-August; 83(7-8):210-20.
23. Disease-Phenotype Deconvolution in Genetic Eye Diseases Using Online Mendelian Inheritance in Man. Pandey P, ACHARYA M* (2016) Invest. Ophthalmol.Vis. Sci.May 1; 57(6):2567-76.
22. Amyloid Beta precursor protein and prion protein have a conserved interaction affecting cell adhesion and CNS development. Kaiser DM#, ACHARYA M#, Leighton PL#, Wang H, Daude N, Wohlgemuth S, Shi B, Allison WT (2012) Plos One. 7(12):e51305. doi: 10.1371/journal.pone.0051305 # equal contribution.
21. Yeast two-hybrid analysis of a human trabecular meshwork cDNA library identified EFEMP2 as a novel PITX2 interacting protein. ACHARYA M, Sharp MW, Mirzayans F, Footz T, Huang L, Birdi C, Walter MA (2012) Mol.Vis. 18:2182-2189.
20. Molecular basis for involvement of CYP1B1 in MYOC upregulation and its potential implication in glaucoma pathogenesis. Mookherjee S, ACHARYA M, Banerjee D, Bhattacharjee A, Ray K (2012) Plos One. 7(9): e45077 doi:10.1371/journal.pone.0045077.
19. A complex regulatory network of transcription factors critical for ocular development and disease. ACHARYA M*, Huang L, Fleisch VF, Allison WT, Walter MA (2011) Hum. Mol. Genet. Apr 15; 20(8):1610-24 *corresponding author.
18. Molecular Genetics of Congenital and Juvenile Glaucoma. ACHARYA M and Walter MA (2010), Encyclopedia of the eye, Elsevier.
17. Human PRKC apoptosis WT1 regulator is a novel PITX2-interacting protein that regulates PITX2 transcriptional activity in ocular cells. ACHARYA M, Lingenfelter DJ, Huang L, Gage PJ, Walter MA (2009) J. Biol. Chem.Dec 11; 284(50): 34829-38.
16. Analysis of mutations of the PITX2 transcription factor found in Axenfeld-Rieger Syndrome patients. Footz T, Idrees F, ACHARYA M, Kozlowski K, Walter MA (2009) Invest. Ophthalmol.Vis.Sci. Jun; 50(6): 2599-606.
15. Complex genetics of glaucoma: Defects in CYP1B1, and not MYOC, cause pathogenesis in an early-onset POAG patient with double variants at both loci. ACHARYA M#, Mukhopadhyay A#, Bhattacharjee A, Thakur SKD, Bandyopadhyay AK, Ray K (2008) J.Genet. 87:3. 265-9. #equal contribution.
14. Leu432Val polymorphism in CYP1B1 as a susceptible factor towards predisposition to primary open-angle glaucoma. Bhattacharjee A, Banerjee D, Mookherjee S, ACHARYA M, Banerjee A, Ray A, Sen A, IGVS, Ray K (2008) Mol. Vis. 14, 841-50.
13. Genetic landscape of the people of India: a canvas for disease gene exploration. Indian Genome Variation Consortium (2008) J.Genet. 87:1. 3-20 Apr.
12. Evaluation of the Opticin gene in primary open angle glaucoma: functional significance of a silent change. ACHARYA M, Mookherjee S, Bhattacharjee A, Thakur SKD, Bandyopadhyay AK, Sen A, Chakrabarti S, Ray K (2007) BMC Mol. Biol., 8:21.
11.Myocilin variants in Indian open angle glaucoma patients. Bhattacharjee A, ACHARYA M, Mukhopadhyay A, Mookherjee S, Banerjee D, Bandyopadhyay AK, Thakur SKD, Sen A, Ray K (2007) Arch.Ophthalmol. 125(6): 823-9.
10. Primary role of CYP1B1 in Indian juvenile-onset POAG patients. ACHARYA M, Mookherjee S, Bhattacharjee A, Bandyopadhyay AK, Thakur SKD, Bhaduri G, Sen A, Ray K (2006) Mol.Vis. 12, 399-404.
9. Role of myocilin in glaucoma: Molecular defects and possible functional aberrations leading to pathogenesis Bhattacharjee A, ACHARYA M, Mookherjee S, Banerjee S, Mukhopadhyay A, Bandyopadhyay AK, Thakur SKD, Sen A, Ray K (2006) Asian J.Experiment. Sci. 20, 97-112.
8. Evaluation of Optineurin as a candidate gene in Indian patients with primary open angle glaucoma. Mukhopadhyay A#, Komatireddy S#, ACHARYA M, Bhattacharjee A, Mandal AK, Thakur SKD, Chandrasekhar G, Bandyopadhyay AK, Thomas R, Chakrabarti S, Ray K (2005), Mol. Vis. 11, 792-97 #equal contribution.
7. Gln48His is the prevalent myocilin mutation in primary open angle and primary congenital glaucoma phenotypes in India. Chakrabarti S, Kaur K, Komatireddy S, ACHARYA M, Devi KR, Mukhopadhyay A, Mandal AK, Hasnain SE, Chandrasekhar G, Thomas R, Ray K (2005), Mol. Vis. 11, 111-13.
6. The Indian Genome Variation database (IGVdb): a project overview. Indian Genome Variation Consortium (2005) Hum. Genet. 118: 1. 1-11 Oct.
5. Genetics and bioinformatics of primary open angle glaucoma: an Indian perspective. Ray K, Thakur SKD, Bandyopadhyay AK, Mukhopadhyay A, ACHARYA M, Bhattacharjee A, Sen A, Bhaduri G (2004), J. Ind. Med. Assoc. 102 (12): 708-12.
4. Myocilin mutation 1109 C>T (Pro 370 Leu) is the most common gene defect causing early onset primary open angle glaucoma. Mukhopadhyay A, ACHARYA M, Ray J, Khan M, Sarkar K, Banerjee AR, Ray K (2003), Ind. J.Ophthalmol. 51 (3), 279-81.
3. Recent Advances in Molecular Genetics of Glaucoma. Ray K, Mukhopadhyay A, ACHARYA M (2003), Mol.Cell. Biochem. 253: 223-31.
2. Mutations in MYOC gene of Indian primary open angle glaucoma patients. Mukhopadhyay A, ACHARYA M, Mukherjee S, Ray J, Choudhury S, Khan M, Ray K (2002), Mol. Vis. 8, 442-48.
1. Distribution of p53 codon 72 polymorphism in Indian primary open angle glaucoma patients. ACHARYA M#, Mitra S#, Mukhopadhyay A, Khan M, Roychoudhury S, Ray K (2002), Mol. Vis.8, 367-71. #equal contribution.
Ms. Shamita Sanga (thesis submitted)
Mr. Sudipta Chakraborty, SRF
Mr. Tahseen Ahmed, SRF
Ms. Sukanya Mitra, SRF
Mr. Jyotishman Sarma, JRF
Ms. Puspita Saha, JRF (jointly with Dr. Mahua Maulik)
Integrated MS-PhD student
Mr. Arun Kumar Mishra
Mr. Shantanu Saha Roy