Chandrama Mukherjee

Assistant Professor

Academic

B.Sc.         Chemistry (Hons), Calcutta University, 1999

M.Sc.         Biochemistry (Molecular Biology as special paper), Calcutta University, 2001

Ph.D.         Bose Institute, Jadavpur University, 2008 on ‘Functional genomics of cell cycle control                          genes in Entamoeba histolytica’.

From my school days, I was motivated to pursue a career in chemistry but this suddenly changed when I took a special course on biochemistry during my undergraduate studies. I started to think about the basic physiological processes, and I was able to connect myself with this vibrant world. I enjoyed going through different elementary courses on biology during my masters in biochemistry. Interactive lecture sessions by professors and various practical classes as follow-up to those theory classes helped me to learn that science is not only limited to text books but this is the real process to study real things. I jumped into the fascinating field of molecular and cell biology and learned various aspects of cell cycle, especially regulation of DNA replication in human parasite Entamoeba histolytica during my PhD under the supervision of Prof. Anuradha Lohia. My PhD training exposed me to various challenges in understanding the cell cycle regulation of the parasite and also encouraged me to pursue my post-doctoral career with another new area of science.

            During my molecular biology classes, I acquired a keen interest for studying the interface of transcription and translation. So I considered exploring this area of science in my postdoctoral carrier. I joined Schoenberg lab as post doctoral researcher in Ohio State University, USA to study post transcriptional regulation. Schoenberg lab gave me a nice opportunity to learn several key features of mammalian cell culture, several techniques approaches to study mRNA decay. Journey through my PhD and post-doc tenure in the different domains of research made me confident about addressing new questions and think independently. I have been also exposed to clinical pharmacogenomics in Dr. Joseph Kitzmiller’s lab for a brief period of time during my post-doc tenure. This very short training in the translational field was extremely beneficial for me since this domain of translational research was completely unknown to me before and it helped me to understand the rationale of pharmacogenomics and personalized medicine. I started my work there to understand effect of statin, a well known drug to lower cholesterol level in patients with cardiovascular diseases, on different ethnic population. Thus I have been exposed to both basic and translational research which helps me immensely to develop my scientific maturity. Being a member of RNA community in OSU also gave me the opportunities to interact with numerous famous RNA biologist, which inspired me to continue my journey as a scientist.

            After spending almost nine years abroad, I returned to India with the dream to start my independent scientific career. I am thankful to Department of Biotechnology for the Ramlingaswami Re-entry fellowship that provided me necessary funds to set up my own lab at Department of Life Sciences, Presidency University. The strength of this department is truely the excellent pool of students, and faculty members with diverse research topics aiming to understand from molecules to the whole organisms.

My newly formed research group ‘RNABio@Presi’ works closely in collaboration with ‘CellBio@Presi’ of Dr. Shubhra Majumder and other groups in the department of Life Sciences.

Research Experience

PhD research brief (2001-2008)

The eukaryotic cell cycle follows strict control mechanisms that ensure faithful duplication and segregation of the genome. However, the cell division cycle of human parasite Entamoeba histolytica shows significant differences with this paradigm. Cells with multiple nuclei and nuclei with varying DNA content (1X-6X) lead to the heterogeneity in the genome content of axenically growing E. histolytica cells, suggesting the regulatory mechanisms of the typical cell cycle are either absent or different in this organism. During the course of my PhD, we strikingly found that the laboratory cultured (axenic) trophozoites of E. histolytica acquired ~ 20-30 fold higher nuclear DNA content compared to the clinical isolates (xenic E. histolytica), indicating that, E. histolytica trophozoites pass through several endo-reduplicative cycles (S-phase without mitosis) during axenisation (stage-conversion) probably due to adaptation with the in vitro culture condition. Thus, endo-reduplication of genome is a fundamental property of this protist parasite and we have also demonstrated that endo-reduplication of the genome occurred within one generation of E. histolytica cells. Our bioinformatics analyses showed that homologs of several proteins required for DNA replication, chromosome segregation or cell divisions were absent or significantly diverged in this organism. We showed that indecisive nature of cytokinesis which might give rise to accumulation of multi-nucleated cells is another key factor leading to the observed heterogeneity in the average DNA content of axenic E. histolytica cells. 

Post-doctoral research brief (2008-2016)

I studied post-transcriptional control of gene expression through changes in mRNA translation and decay. The methylguanosine ‘cap’ (m7G) that is added by Capping Enzyme (CE) to all mRNAs plays a central role in translation initiation. Proteins that bind the cap facilitate splicing, polyadenylation, export and surveillance of mRNAs. The Schoenberg lab identified a cytoplasmic pool of CE (cCE) that, unlike nuclear CE, acts with an unidentified 5’-polynucleotide RNA kinase to restore the cap onto uncapped RNAs in the cytoplasm. My postdoctoral studies in the Schoenberg lab identified mRNA targets regulated by cytoplasmic capping. In the course of this work we also identified a cyclical process of decapping and recapping, termed ‘cap homeostasis’. Inhibition of cytoplasmic capping destabilized some target transcripts and caused the redistribution of other transcripts from translating polyribosomes to nontranslating messenger ribonucleoprotein fractions. The identification of cytoplasmic capping represents a paradigm shift in our understanding of the mRNA cycle and post-transcriptional gene expression. By demonstrating that a presumed irreversible process is in fact reversible, our finding expands upon the role of decapping in mRNA decay, and in doing describes a previously unrecognized post-transcriptional mechanism governing the cycling of mRNAs between active (translating) and inactive (non-translating) states. These targets encode proteins involved in nucleotide binding, RNA and protein localization and in regulation of cell cycle. While investigating the assembly of capping complex in cytoplasm, I identified Nck1, a cytoplasmic adaptor protein containing three SH3 and one SH2 domain as a cCE-interacting protein, and I showed Nck1 functions as the scaffold for assembling the cytoplasmic capping complex. I identified RNA methyl transferase as another component of cytoplasmic capping complex that likely adds the methyl group to capped RNA and other interesting candidate proteins as cCE interactors using LC-MS/MS. Identification of the mRNA targets and interactions of cytoplasmic Capping Enzyme leads to determine whether cytoplasmic capping is involved in the reactivation of mRNAs that are stored or silenced by microRNAs.

Post-doctoral research brief (2016-2017)

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors or statins are recommended as candidate drugs for the treatment of hypercholesterolemia and prevention of cardiovascular disease. Though this drug has been used for long time effectively, potential side effects also have been reported worldwide. The level of efficacy of the drug as well as the potential side effects has been shown to vary with ethnicity. Primarily the single nucleotide polymorphisms (SNPs) contribute to the difference in drug efficacy. Our team has identified the SNPs responsible for this difference in African-American population. Further studies using large cohort of patients are required to understand the pharmacogenomics of statins to develop personalized medicine.

Current research

The generalized repression of cap-dependent translation is one of the earliest responses to cell stress. Non-translating mRNAs accumulate in stress granules (SGs) and processing bodies (PBs), and this is also associated with changes in the turnover of selected mRNAs. Thus, post-transcriptional reprogramming of mRNA translation and decay reconfigures the proteome during adverse environmental conditions as well as recovery from stress. Perturbations in RNA granule functions lead to pathological phenotypes observed in multiple neurodegenerative, immunological and infectious diseases, and SGs were recently shown to promote the formation of metastasis. Earlier work from our lab demonstrated that interfering with cytoplasmic capping reduced the ability of cells to recover from a brief oxidative stress. The concept of cytoplasmic capping is quite new and it starts to gain attention in last five years. Cytoplasmic capping impacts the transcriptome at the post-transcriptional level with addition of a cap at the 5’ end of uncapped RNA. Thus it may expand the proteome by generating new truncated proteins lacking 5’ terminus from recapped RNAs without affecting the transcriptome. This is a novel idea so far, but some studies across the world show evidences of new short proteins or peptides of unknown function. Earlier work demonstrated that interfering with cytoplasmic capping reduced the ability of cells to recover from a brief oxidative stress. Some of my preliminary data suggested a similar trend. Based on these findings, I hypothesize that recapping of mRNAs in the cytoplasm plays a central role in cellular recovery from stress. I will test my hypothesis using following aims.

Aim-1. What is the role of  cytoplasmic Capping Enzyme in response to stress?

Aim-2. What is the impact of cellular stress on the recapped transcriptome?

Administrative Experience:

I am involved in different internal committees of the School of Biotechnology at Presidency University.

Teaching experiences:

I was deeply influenced by my teachers during my journey as a student.In the light of recent discoveries in the field of regulation of transcription, translation and functional genomics of eukaryotes, I like to teach the biochemistry of gene expression. This course would include but not limited to-i) discussion about cellular organelles focusing the structure of nucleus, ii) chromatin structure and modification, iii) molecular regulation of replication, transcription and translation, iv) post-transcriptional regulation of gene expression, v) post-translational modification with special emphasis on RNA biochemistry, stress response mechanism and the emerging role of non coding RNAs in regulating gene expression, vi) regulation of eukaryotic cell cycle, maintenance of checkpoints in normal and tumor cells. In addition, I would also like to train a course on role of RNA binding proteins in various diseases, in particular neurodegenerative diseases as there is growing evidences of RNA binding proteins in disease progression. I would like to share with my students the new discoveries relevant to the field of their study so that they could relate themselves with the world. As a teacher I aim to provide my students with the analytical skills useful in biology, including the ability to think and the capability to learn outside the traditional classroom setting. This will also help them to think in a broader way beyond the textbooks.

Even semester-2018 (Jan-April):

mRNA translation control, RNA interference (miRNA & siRNA)- as part of postgraduate theory course- ‘Advanced genetics’, BIOS0802, (Sem-2)

Organization of bacterial genome. Structure of Eukaryotic genomes, non-repetitive and repetitive DNA sequences, Mitochondrial DNA organization, Chloroplast genome organization. RNA polymerase and the transcription cycle in bacteria, a brief overview on transcription in eukaryotes, Translation mechanism in prokaryotes, The Genetic Code, Codon Anticodon interaction, Ribosomes, A brief overview on Protein Synthesis in Eukaryotes- as part of undergraduate theory course-‘Maintenance, expression and regulation of the genome’, (BIOS0402D), (Sem-2),

Odd semester-2018 (Aug-Nov):

‘Histochemical and immunocytochemical techniques: Antibody generation, detection of molecules using ELISA, RIA, Western Blot, immunoprecipitation, flow Cytometry and immunofluorescence microscopy, detection of molecules in living cells, in situ localization by techniques such as FISH and GISH’, - as part of postgraduate theory course -‘Methods and Experimental Design’, BIOS0701, (Sem-1)

‘Brief overview of synthesis of RNA in prokaryotes’ as part of undergraduate theory course on ‘Molecular Biology’, BIOS0301, (Sem-1)

‘MO Approach: limitations of the VB approach, salient features of the MO theory. Rules for the LCAO method, bonding and anti-bonding MOs and their characteristics for s-s-, s-p and p-p combinations of atomic orbitals, nonbonding combinations of orbitals. as part of undergraduate theory course- ‘Chemical Bonding and Molecular Structure Ionic Bonding’, BIOS01C1, (Sem-1)

Training on some basic instruments as part of Paper III (Care and Use of Common  Laboratory Equipment/ Facilities) for PhD course

Professional experiences:

Ad hoc Reviewer- WIREs RNA, FEBS Letters

Judge- Denman Undergraduate Research Forum, Ohio State University (2013-2016)

Organizer- Member of the Organizing committee, Regional Young Investigators Meeting, Kolkata, 2019

I am looking for highly motivated and enthusiastic students preferably with CSIR/DBT -JRF fellowship to work in my group. Interested people may contact me at

chandrama.dbs@presiuniv.ac.in with their CV and research of interest.

Current lab members

1.      Anakshi Gayen                 M.Sc., SRF

2.      Avik Mukherjee                M.Sc., SRF

3.      Safirul Islam                     M.Sc., UGC-SRF

4.      Manisha Das                    M. Sc, JRF

Disseration student 

Pinaki Ghosh, MSc Sem IV student, IHS, PU

Arpita Patra, MSc Sem IV student, IHS, PU

Summer Intern 

Moumita Ghosh, 1st Sem, MSc in Biotechnology, Amity University, Kolkata

Past lab member

1. Saheli Saha                 PhD at IISC, Bengaluru

2. Arundhati Karmakar     Summer trainee; PU DLS, 3rd Sem UG student of 2017-20

3. Anurita Halder              Summer trainee; PU DLS, 3rd Sem UG student of 2017-20

 4. Ranu Soren                 M.Sc. dissertation student, PU DLS of 2017-19

5.  Soumi Saha                 M.Sc. dissertation student, PU DLS of 2017-19, Presently enrolled in PhD program at WBSU

6. Tithi Bhandari              Summer trainee, NISER, Odisha

7. Anirban Kundu           Summer trainee, Benaras Hindu University

8. Nivedita Mukherjee   M.Sc. dissertation student, PU DLS of 2018-20, presently doing PhD in NCBS, Bengaluru

9. Ananya Chatterjee               M.Sc. dissertation student, PU DLS of 2018-20, presently enrolled  in PhD program at IIT, Kharagpur

10. Sourav Mukherjee    Project assistant, currently enrolled in PhD program  in Bombay IIT

11.      Saitali Laha Roy  Project Assistant, currently enrolled in PhD program in Bombay IIT

12. Souvik Chakraborty M.Sc. dissertation student, PU SBT of 2019-2021

13. Somnath Panda, 4th Sem, MSc in Biotechnology, Maulana abul kalam university of technology, West Bengal

14. Piyush Jaiswal,  1st Sem, MSc in Human Genetics & Molecular Biology, Bharathiar University, Coimbatore, Tamil Nadu

15. Nilabhra Ghosh, 1 st Sem, MSc in Biotechnology, Viswa Bharati University

American Heart Association : 2013-2015

RNA Society: 2009-Present

RNA group (India): 2022-Present

Guest Editor of Frontiers in Genetics and Development

Reviewer: MDPI, NAR Cancer, Khorana summer program

Publications (in reverse chronological order)

Chakraborty P. and Mukherjee C. (2024) The interplay of metabolic and epigenetic players in disease development. Biochem Biophy Res Communication 29: 734:150621 (Online ahead of print).

Islam S. and Mukherjee C. (2024) Preprint: Cytoplasmic mRNA capping enzyme is regulated by hypoxia inducible factor HIF1α and controls stability of the target lncRNAs during hypoxia.

Gayen A., Mukherjee A., Kumar K., Majumder S., Chakrabarti S., and Mukherjee C. (2024) The mRNA-capping enzyme localizes to stress granules in the cytoplasm and maintains cap homeostasis of target mRNAs. Journal of Cell Science 137(11): jcs261578.

Dutta A., Halder P., Gayen A,,  Mukherjee A,  Mukherjee C.,  and Majumder S*. (2023) Increase in primary cilia number and length upon VDAC1 depletion contributes to attenuated proliferation of cancer cells. Exp Cell Res. June 3

 Gayen A., Mukherjee A., Majumder S.  and Mukherjee C*. (2023)Preprint: mRNA capping enzyme exports to cytoplasm, localizes to stress granules and maintains cap homeostasis of the target mRNAs

Mukherjee A., Islam S., Kieser R.E., Kiss D.L., Mukherjee C.* (2023) Long non-coding RNAs are substrates for cytoplasmic capping enzyme. FEBS Letters. March 1

Islam, S and Mukherjee C. (2022) Molecular regulation of hypoxia through the lenses of non- codingRNAs and epitranscriptome. WIREs RNA (online publication:July 3, 2022). https://doi.org/10.1002/wrna.1750

Mukherjee, N. and Mukherjee C. (2021) Germ cell ribonucleoprotein granules in different clades
of life: From insects to mammals. WIREs RNA, e1642.

Mukherjee C., Sweet K. M., Luzum J. A., Abdel-Rasoul M., Christman M.F. and Kitzmiller J.P. (2017) Clinical pharmacogenomics: patient perspectives of pharmacogenomic testing and the incidence of actionable test results in a chronic disease cohort. Personalized Medicine, 14: 5.

Trotman J., Giltmier A., Mukherjee C., and Schoenberg D.R. (2017) RNA guanine-7- methyltransferase catalyzes the methylation of cytoplasmically recapped RNAs. Nucleic Acids Research, 45(18) 10726–10739.

Kitzmiller J.P., Mikulik E.B, Dauki A.M., Mukherjee C. and Luzum J.A. (2016) Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmacogenomics and Personalized Medicine, 2016: 9: 97–106.

Kiss D., Kenji O.*, Dougherty J.*, Mukherjee C.*, Bundschuh R., and Schoenberg D.R. (2015) Cap homeostasis is independent of poly(A) tail length. Nucleic Acid Research, 44(1): 304-14. (* equal contribution).

Mukherjee C., Bakthavachalu B., and Schoenberg D.R. (2014) The cytoplasmic capping complex assembles on adapter protein Nck1 bound to the proline-rich C-terminus of mammalian capping enzyme. PLoS Biology, 12(8): e1001933.

Mukherjee C.*, Patil D.P.*, Kennedy B.A., Bakthavachalu B., Bundschuh R., Schoenberg D.R. (2012) Identification of cytoplasmic capping targets reveals a role for cap homeostasis in translation and mRNA stability. Cell Reports, 2(3): 674-84. (* equal contribution); Selected as ‘Resource’ article.

Mukherjee C.*, Majumder S.*, and Lohia A. (2009) Inter-cellular variation in DNA content of Entamoeba histolytica originates from temporal and spatial uncoupling of cytokinesis from the nuclear duplication cycle. PLoS Neglected Tropical Disease, 3(4): e409. (* equal contribution) (Image selected for ‘Cover Photo’); Selected for discussion in the ‘Editor’s Choice’ section, Science, 324(5931): 1119.

Mukherjee C., Clark C.G., and Lohia A. (2008) Entamoeba shows reversible variation in ploidy under different growth conditions and between life cycle phases. PLoS Neglected Tropical Disease, 2(8): e281.

Clark C.G., Alsmark U.C.M., Hofer M., Saito-Nakano Y., Ali V., Marion S., Weber C., Mukherjee C., Bruchhaus I., Tannich E., Leippe M., Sicheritz-Ponten T., Foster P.G., Samuelson J., Noël C., Hirt R.P., Embley T.M., Gilchrist C.A., Mann B.J., Singh U., Ackers J.P., Bhattacharya S., Bhattacharya A., Lohia A., Guillén N., Duchêne M., Nozaki T., and Hall N. (2007)Structure and Content of the Entamoeba histolytica Genome. Advances in Parasitology, 65: 51-190.

Loftus B., Anderson I., Davies R., Alsmark U.C., Samuelson J., Amedeo P., Roncaglia P., Berriman M., Hirt R.P., Mann B.J., Nozaki T, Suh B., Pop M., Duchene M., Ackers J., Tannich E., Leippe M., Hofer M., Bruchhaus I., Willhoeft U., Bhattacharya A., Chillingworth T., Churcher C., Hance Z., Harris B., Harris D., Jagels K., Moule S., Mungall K., Ormond D., Squares R., Whitehead S., Quail M.A., Rabbinowitsch E., Norbertczak H., Price C., Wang Z., Guillen N., Gilchrist C., Stroup S.E., Bhattacharya S., Lohia A., Foster P.G., Sicheritz-Ponten T., Weber C., Singh U., Mukherjee C., El-Sayed N.M., Petri W.A. Jr., Clark C.G., Embley T.M., Barrell B., Fraser C.M., and Hall N. (2005) The genome of the protist parasite Entamoeba histolytica. Nature, 433: 865-868. 

Das S., Mukherjee C., Sinha P., and Lohia A. (2005) Constitutive association of Mcm 2-3-5 proteins with chromatin in Entamoeba histolytica. Cellular Microbiology, 7: 259-267.

Other publications, reviews

Abstract 1121: Identifying novel cytoplasmic mRNA capping enzyme-targeted, hypoxia-responsive RNAs in hypoxic osteosarcoma cellular model: A plausible therapeutic approach

Islam S, Bakshi U,  Mukherjee  C- Journal of Biological Chemistry, 2024

Editorial: Role of non-coding RNAs in development and metastasis of solid tumours
B Roy, S Dutta, C Mukherjee*
Frontiers in Cell and Developmental Biology 
 

Lohia A., Mukherjee C., Majumder S., and Ghosh Dastider P. (2007) Genome re-duplication and irregular segregation occur during the cell cycle of Entamoeba histolytica. Bioscience Reports, 27: 373-384. (Review)

Mukherjee C., Majumder S., Ghosh Dastider P. and Lohia A. (2007) Endoreplication and irregular division lead to heterogeneity of genome content in Entamoeba histolytica. Tropical Medicine & International Health, 12: 30-31. (Brief report).