Dr. Arnab Mukhopadhyay
Research Interest:
Summary of Research:Longevity, dietary restriction, diet-gene interactions, Insulin-IGF-1 signalling pathway, metabolism, stress response, germline development, reproductive aging, cell signaling, cross-tissue communications.
The primary focus of my lab is to understand the molecular mechanisms that determine the longevity of an organism. The main interests of the lab are:
- Diet-gene interactions that regulate longevity
- Regulation of the Insulin-IGF-1 signaling pathway
- Regulation of oogenesis and reproductive aging by nutrient-sensing pathways
- The biology of Dietary restriction
- Understanding molecular link between aging and innate immune pathways
- Screening for novel compounds that extend longevity
We use a combination of molecular biology, genomics, Next Generation sequencing and molecular genetics approaches in the lab. Caenorhabditis elegans is the system of choice for our studies due to its short and reproducible life span, low maintenance cost, amenability to high throughput molecular techniques as well as ease of genetic manipulation. Interestingly, the molecular makeup of the innate immune response pathways and those that regulate longevity are strikingly similar between vertebrates and invertebrates. Such conservations are a key to extrapolating the results obtained in our model system and validating them in mammals.
Group Members:
Umanshi Rautela, Sabnam Sahin Rahman, Simran Motwani, Jasleen Kaur, Sonu Gupta, Pankaj Mahto, Nitika Arora and Shreya Putatunda
Visiting students : Nafees Ansari, Animesh Kar, Nafees Ansari, Trishna Pani
Umanshi Rautela, Sabnam Sahin Rahman, Simran Motwani, Jasleen Kaur, Sonu Gupta, Pankaj Mahto, Nitika Arora and Shreya Putatunda
Visiting students : Nafees Ansari, Animesh Kar, Nafees Ansari, Trishna Pani
Awards:
• JC Bose Fellowship (2023)
• Elected Fellow, Indian National Science Academy (INSA), 2021.
• SERB-Science Technology Award for Research (STAR) award, 2019
• Elected Fellow, The National Academy of Sciences (NASI), India, 2019
• Elected Member of Guha Research Conference (GRC) (2017)
• National Bioscience Award for Career Development (2016), Department of Biotechnology, Govt. of India
• Ramalingaswami Fellowship (2009-2014), Department of Biotechnology, Govt. of India
Publications:
- Sarkar GC*^, Rautela U*, Goyala G*, Datta S, Anand N, Singh A, Singh P, Chamoli M, Mukhopadhyay A^ (2022) A cell non-autonomous FOXO/DAF-16-mediated germline quality assurance program that responds to somatic DNA damage. Development 150 (17): dev201472. DOI:10.1242/dev.201472
- Singh P*, Gollapalli K*……....Nair T……….. Kennedy BK, Andersen JK, Lithgow GJ, Ali AM, Mukhopadhyay A, Palotie A, Kastenmüller G, Kaeberlein M, Wackerhage H, Pal B, Yadav VK^ (2023) Taurine deficiency as a driver of aging. Science 280 (6649):1-11. DOI:10.1126/science.abn9257
- Kar A*, Jain D*, Kumar S, Rajput K, Pal S, Rana K, Kar K, Jha SK, Medatwal N, Yavvari PS, Pandey N, Mehta D, Sharma H, Bhattacharya D, Pradhan MK, Datta Sharma R, Srivastava A, Agarwal U, Mukhopadhyay A, Sengupta S, Patil VS, Bajaj A^, Dasgupta U^ (2023) A Localized Hydrogel-mediated Chemotherapy Causes Immunogenic Cell Death via Activation of Ceramide-mediated Unfolded Protein Response. Science Advances 9: eadf2746. DOI:10.1126/sciadv.adf2746
- Nair T and Mukhopadhyay A^ (2023) Diet-gene interactions ensure optimal life span and health. J Biosci (in press)
- Garg A, Alam M, Bai S, Dandawate M, Kumari N, Gupta S, Agrawal U, Nagarajan P, Reddy DS, Kulkarni MJ, and Mukhopadhyay A^ (2023) Protective Effects of Rifampicin and Its Analog Rifampicin Quinone in a Mouse Model of Obesity-Induced Type 2 Diabetes. ACS Pharmacology and Translational Science 6(2): 253–269. [http://doi.org/10.1021/acsptsci.2c00082]
- Sarkar GC, Rautela U*, Goyala G*, Datta S, Anand N, Singh A, Singh P, Chamoli M, Mukhopadhyay A^ (2022) A cell non-autonomous FOXO/DAF-16-mediated germline quality assurance program that responds to somatic DNA damage. bioRxiv 2022.03.03.482777 (doi: https://doi.org/10.1101/2022.03.03.48277.7)
- Nair T, Chakraborty R, Singh P, Rahman SS, Bhaskar AK, Sengupta S and Mukhopadhyay A (2022) Adaptive capacity to dietary Vitamin B12 levels is maintained by a gene-diet interaction that ensures optimal life span. Aging Cell 21(1):e13518. (https://doi.org/10.1111/acel.13518).
- Mukhopadhyay A, Malakar D, Maiti T, Arimbasseri AG, Deo SVS, Datta Sharma R, Bajaj A, and Dasgupta U^ (2021) Alternative Splicing of Ceramide Synthase 2 Alters Levels of Specific Ceramides and Modulates Cancer Cell Proliferation and Migration in Luminal B Breast Cancer Subtype. Cell Death and Disease 12(2):171.
- Sreekanth V, Kar A, Kumar S, Pal S, Yadav P, Sharma Y, Komalla V, Sharma H, Shyam R, Sharma RD, Mukhopadhyay A, Sengupta S, Dasgupta U^, and Bajaj A^ (2020) Bile Acid Tethered Docetaxel‐based Nanomicelles Mitigate Tumor Progression through Epigenetic Changes. Angewandte Chemie International Edition (in press) https://doi.org/10.1002/anie.202015173
- Goyala A, Baruah A and Mukhopadhyay A (2020) The genetic paradigms of dietary restriction fail to extend life span in cep-1(gk138) mutant of C. elegans p53 due to possible background mutations, PLoS One 15(11):e0241478. DOI:10.1371/journal.pone.0241478
- Chamoli M*, Goyala A*, Tabrez SS*, Siddiqui AA, Singh A, Antebi A, Lithgow GJ, Watts JL and Mukhopadhyay A (2020) Polyunsaturated fatty acids and p38 MAPK pathway link metabolic reprogramming to cytoprotective gene expression during Dietary Restriction. Nature Communications 11 (1), 1-13. *Co-first author
- Matai L*, Sarkar GC*, Chamoli M, Malik Y, Kumar SS, Rautela U, Jana NR, Chakraborty K^, Mukhopadhyay A^ (2019) Dietary restriction improves proteostasis and increases life span through Endoplasmic Reticulum hormesis. Proceedings National Academy of Sciences USA 116 (35) 17383-17392.*Co-first author, ^Co-senior authors
- Kumar N and Mukhopadhyay A (2019) Using ChIP-based approaches to characterize FOXO recruitment to its target promoters. Methods in Molecular Biology 1890:115-130. DOI: 10.1007/978-1-4939-8900-3_10.
- Verma S, Jagtap U, Goyala A, Mukhopadhyay A (2018) A novel gene-diet pair modulates C. elegans aging. PLOS Genetics (DOI:10.1371/journal.pgen.1007608)
- Tabrez SS, Datta Sharma R, Jain V, Siddiqui AA and Mukhopadhyay A (2017) Differential alternative splicing coupled to nonsense-mediated decay of mRNA ensures dietary restriction-induced longevity. Nature Communications (DOI: 10.1038/s41467-017-00370-5).
- Maity S*, Rajkumar A*, Matai L*, Bhat A, Ghosh A, Agam G, Kaur S, Bhatt NR, Mukhopadhyay A^, Sengupta S^, Chakraborty C^ (2016) Oxidative homeostasis regulates response to reductive Endoplasmic Reticulum stress through translation control. Cell Reports 16, 851–865. *Co-first author, ^Equally contributing senior authors
- Singh A, Kumar N, Matai L, Garg A and Mukhopadhyay A (2016) A chromatin modifier integrates insulin/IGF-1 signalling and dietary restriction to regulate longevity. Aging Cell 15:694–705.
- Kumar N^, Jain V*, Singh A*, Jagtap U, Verma S and Mukhopadhyay A^ (2015) Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans. Oncotarget 6(39):41418-33. *Equal contributions, ^Corresponding authors
- Golegaonkar S*, Tabrez SS*, Pandit A, Shalini S, JagadeeshaPrasad MG, Bansode S, Sampathkumar SG, Kulkarni MJ^ and Mukhopadhyay A.^ (2015) Rifampicin reduces Advanced Glycation End products and activates DAF-16 to increase life span in Caenorhabditis elegans. Aging Cell 14(3):463-73. doi: 10.1111/acel.12327. *Co-first authors, ^Corresponding authors
- Pandit A, Jain V, Kumar N, and Mukhopadhyay A. (2014) PHA‐4/FOXA‐regulated microRNA feed forward loops during Caenorhabditis elegans dietary restriction. Aging 6(10): 835-851.
- Chamoli M, Singh A, Malik Y, Mukhopadhyay A. (2014) A novel kinase regulates Dietary Restriction-mediated longevity in C. elegans. Aging Cell 13(4):641-55. doi: 10.1111/acel.12218.
- Ritter AD, Shen Y, Fuxman Bass J, Jeyaraj S, Deplancke B, Mukhopadhyay A, Xu J, Driscoll M, Tissenbaum HA, Walhout AJ. (2013) Complex expression dynamics and robustness in C. elegans insulin networks. Genome Res. 23(6):954-65.
- Parker JA, Vazquez-Manrique RP, Tourette C, Farina F, Offner N, Mukhopadhyay A, Orfila AM, Darbois A, Menet S, Tissenbaum HA, Neri C. (2012) Integration of ß-catenin, sirtuin, and FOXO signaling protects from mutant huntingtin toxicity. J Neurosci 32:12630-40.
- Padmanabhan S*, Mukhopadhyay A*, Narasimhan S*, Tesz G, Czech MP, Tissenbaum HA (2009) A PP2A regulatory subunit, PPTR-1, regulates C. elegans insulin signaling by modulating AKT-1 phosphorylation. Cell1 36:939-951.*Co-first author paper
- Mukhopadhyay A*, Deplancke B*, Walhout AJM, Tissenbaum HA (2008) Chromatin immunoprecipitation (ChIP) coupled to detection by quantitative real-time PCR to study transcription factor binding to DNA inCaenorhabditis elegans. Nature Protocols 3:698-709. *Co-first author paper
- Mukhopadhyay A, Pan X, Lambright D, Tissenbaum HA (2007) An endocytic pathway as a target of tubby for regulation of fat storage. EMBO Reports 8:931-938.
- Deplancke B, Mukhopadhyay A, Ao W, Elewa AM, Grove CA, Martinez NJ, Sequerra R, Doucette-Stamm L, Tissenbaum HA, Mango SE, Walhout AJM (2006) A gene-centered C. elegans protein-DNA interaction network. Cell 125:1193-205.
- Oh SW*, Mukhopadhyay A*, Dixit BL, Raha T, Green MR, Tissenbaum HA (2006) Identification of direct DAF-16 targets controlling longevity, metabolism and diapause by chromatin immunoprecipitation. Nature Genetics 38:251-257. *Co-first author paper
- Mukhopadhyay A, Deplancke B, Walhout AJM, Tissenbaum HA (2005) C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell Metabolism 2:35-41.
- Oh SW, Mukhopadhyay A, Svrzikapa N, Jiang F, Davis RJ, Tissenbaum HA (2005) JNK regulates life span in C. elegans by modulating nuclear translocation of FOXO/DAF-16. Proceedings National Academy of Sciences USA 102:4494-4499.
