Dr. Aneeshkumar A.G.
Summary of Research:
Nutrients, metabolism and gene expression
A healthy life depends on the balance between nutrient uptake and the metabolism of the individual. While macronutrients (fat, carbohydrates and protein) serve as the source of both energy and structural building blocks of the organism, micronutrients such as vitamins and minerals are required for various physiological processes including energy metabolism.
The interaction between micronutrients and macronutrients sets the stage for a complex interaction network of different metabolic pathways, the outcome of which will determine the health of the individual. Deregulation of such interaction networks can have long-term effects on health.
Recent national surveys have identified Vitamin D deficiency as a major form of malnutrition in India. It is associated with metabolic disorders and immune dysfunction.
Vitamin D is required for functioning of multiple organ systems including muscles, bones, intestines etc. But how its requirements and functions vary under different metabolic and pathological conditions is not known. Since metabolic homeostasis involves multiple organs, an imbalance in one system affects others leading to a domino effect. An integrated understanding of the role of vitamin D in intra- and inter-organ interactions that maintain metabolic homeostasis is essential to devise next-generation public health policy regarding nutritional requirements.
Our work revolves around the premise that the requirements and functions of micronutrients depend on feeding habits and the ratio of different macronutrients in the staple diet.
To elucidate the effects of nutrient-metabolic interactions, we employ a systems level approach that integrates multiple organ systems. We use genomics and molecular biology tools to elucidate the effect of nutrient-metabolic interactions in different vitamin D target organs/tissues including skeletal muscle, liver, intestine, and bones.
Maintenance of metabolic homeostasis by vitamin D
(for more details, please see lab website: https://sites.google.com/nii.ac.in/molgenlab/home)
Recently we have shown that in the absence of systemic vitamin D signalling, skeletal muscles of mice exhibit a glycogen storage disorder characterized by increased glycogen synthase, reduced glycogen phosphorylase and lower glycogen branching enzyme. Glycogen storage deregulation in muscles is also associated with other diseases including McArdle disease (Das et al., 2022). We have also shown that specially formulated milk-based diets could restore muscle energy levels by circumventing the need for glycogen as energy source (Das et al., 2023).
Metabolic regulation of gene expression in immune cells
(for more details, please see lab website: https://sites.google.com/nii.ac.in/molgenlab/home)
We are also interested in understanding how gene regulation is altered by metabolism at cellular level. We use immune cells as a model system to study this. We have shown that resting state B cells exhibit increased protein synthesis due to higher levels of mTORC1 activity (Khalsa et. al., 2019, Dev et. al., 2022).
Group Members:
Khem Singh Negi, Neha Jawla, Somdeb Chattopadhyay, Chen Chongtham, Trisha Biswas, Archana Pant, Vaidehee, Shubhi Khare, Mohtashim Rosh, Namaste Kumari, S. Jayalakshmi
Khem Singh Negi, Neha Jawla, Somdeb Chattopadhyay, Chen Chongtham, Trisha Biswas, Archana Pant, Vaidehee, Shubhi Khare, Mohtashim Rosh, Namaste Kumari, S. Jayalakshmi
Publications:
- Soman S, Chattopadhyay S, Ram S, Nandicoori VK, Arimbasseri GA. (2023) Codon optimality has minimal effect on determining translation efficiency in mycobacterium tuberculosis. Sci Rep. 13(1):415. doi: 10.1038/s41598-022-27164-0. PMID: 36624167
- Dev G, Chawla AS, Gupta S, Bal V, George A, Rath S, Arimbasseri GA. (2022) Differential Regulation of Two Arms of mTORC1 Pathway Fine-Tunes Global Protein Synthesis in Resting B Lymphocytes. Int J Mol Sci. 23(24):16017. doi: 10.3390/ijms232416017.
- Ratra Y, Kumar N, Saha MK, Bharadwaj C, Chongtham C, Bais SS, Medigeshi G, Arimbasseri GA, Basak S. (2022) A Vitamin D-RelB/NF-κB Pathway Limits Chandipura Virus Multiplication by Rewiring the Homeostatic State of Autoregulatory Type 1 IFN-IRF7 Signaling. J Immunol. 209 (3): 559–568 . doi: 10.4049/jimmunol.2101054.
- Kumar S, Khan MZ, Khandelwal N, Chongtham C, Singha B, Dabla A, Behera D, Singh A, Gopal B, Arimbasseri GA, Kamat SS, Nandicoori VK. (2022) Mycobacterium tuberculosis Transcription Factor EmbR Regulates the Expression of Key Virulence Factors That Aid in Ex Vivo and In Vivo Survival. mBio. e0383621. doi: 10.1128/mbio.03836-21.
- Das A, Gopinath SD, Arimbasseri GA. (2021) Systemic ablation of vitamin D receptor leads to skeletal muscle glycogen storage disorder in mice. J. Cachexia, Sarcopenia and Muscle. 13(1):467-480. DOI: 10.1002/jcsm.12841. PMID: 34877816
- Pani T, Rajput K, Kar A, Sharma H, Basak R, Medatwal N, Saha S, Dev G, Kumar S, Gupta S, Mukhopadhyay A, Malakar D, Maiti TK, Arimbasseri AG, Deo SVS, Sharma RD, Bajaj A, 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 Dis. 12(2):171. doi: 10.1038/s41419-021-03436-x. PMID: 33568634
- Mishra S, Sevak JK, Das A, Arimbasseri GA, Bhatnagar S, Gopinath SD. (2020) Umbilical cord tissue is a robust source for mesenchymal stem cells with enhanced myogenic differentiation potential compared to cord blood. Sci Rep. 10(1):18978. doi: 10.1038/s41598-020-75102-9. PMID: 33149204
- Umar D, Das A, Gupta S, Chattopadhyay S, Sarkar D, Mirji G, Kalia J, Arimbasseri GA, Durdik JM, Rath S, George A, Bal V. (2020) Febrile temperature change modulates CD4 T cell differentiation via a TRPV channel-regulated Notch-dependent pathway. Proc Natl Acad Sci U S A. DOI: 10.1073/pnas.1922683117 (PMID: 32839313)
- Chawla AS, Khalsa JK, Dhar A, Gupta S, Umar D, Arimbasseri GA, Bal V, George A, Rath S. (2020) A role for cell-autocrine interleukin-2 in regulatory T-cell homeostasis, Immunology, 160(3):295-309. doi: 10.1111/imm.13194 (PMID: 32187647)
- Dhar A, Chawla M, Chattopadhyay S, Oswal N, Umar D, Gupta S, Bal V, Rath S, George A, Arimbasseri GA, Basak S. (2020) Role of NF-kappaB2-p100 in regulatory T cell homeostasis and activation. Sci Rep. 9(1):13867. doi: 10.1038/s41598-019-50454-z (PMID: 31554891)
- Bhalla P, Shukla A, Vernekar DV, Arimbasseri AG, Sandhu KS, Bhargava P. (2019) Yeast PAF1 complex counters the pol III accumulation and replication stress on the tRNA genes. Sci Rep., 9(1):12892. doi: 10.1038/s41598-019-49316-5
- Khalsa JK, Chawla AS, Prabhu SB, Vats M, Dhar A, Dev G, Das N, Mukherjee S, Tanwar S, Banerjee H, Durdik JM, Bal V, George A, Rath S*, Arimbasseri GA*. Functionally significant metabolic differences between B and T lymphocyte lineages. Immunology. 158(2):104-120. doi: 10.1111/imm.13098 (PMID: 31318442) *co-corresponding author
- Arimbasseri GA. (2018) Interactions between RNAP III transcription machinery and tRNA processing factors. Biochim Biophys Acta Gene Regul Mech. 1861(4):354-360. doi: 10.1016/j.bbagrm.2018.02.003 (PMID: 29428193)
