Research focus: Cell biology of ciliogenesis and centrosome assembly
I am a researcher in cell and molecular biology. I studied chemistry, and then was trained in Protein chemistry, and Cell and Molecular biology during my PhD and post-doctoral tenure. I teach various areas of chemistry, biophysical chemistry, and cell biology of PG and PhD courses.
The current focus of my research group CellBioLab evolves around understanding molecular mechanism of centriole and cilia assembly, the interconversion of centriole and basal body, and the disease biology associated with dysfunction of cilia and supernumerary centrioles.
Centrioles either form the core of a centrosome, or transform into basal bodies that assemble motile or non-motile primary cilia. Centrosomes are precisely duplicated during S-phase, and serve as the poles of the mitotic spindle, thereby ensuring the maintenance of genomic integrity. Primary cilia that are microtubule-based and membrane-ensheathed projections from cell surface transduce physiological signals, such as- hedgehog signaling during development (SHH in mammals). Generally, during cellular quiescence, the distal end of the oldest centriole of a centrosome is encapsulated by golgi-derived vesicles and is docked to the apical membrane to transform into basal body. The basal body, utilizing the activity of intraflagellar transport (IFT) machinery, assembles the cilium. Cilia are resorbed once cells enter the S-phase, allowing centrioles to participate in centriole assembly. These coordinated events are responsible to maintain centriole homeostasis. Ciliary dysfunction is associated with various human disorders collectively known as ciliopathies. On the other hand, excess centrioles occur in various solid tumor tissues, and are indeed seen to resulting in chromosome segregation error, thereby leading aneuploidy that is a hallmark of most cancers.
We will assess novel regulators of centriole and primary cilia assembly such as actin cytoskeleton modulators, Voltage Dependent Anion Channels (VDAC), cytosolic dynein, cell cycle regulating kinases, replication controlling proteins, and the modulators of RNA and RNA-binding proteins enriched granules.
The two major questions that we ask are-
Aim-1: How does cytoskeleton rearrangement regulate ciliogenesis?
Aim-2: How do the VDACs regulate centriole assembly and ciliogenesis?
Aim-3: Molecular connection between cellular metobolic status and ciliogensis in cancer cells.
Education (chronological order)
B.Sc. (1999)- Chemistry (Major), Physics, Mathematics (minor); (from Calcutta University)
M.Sc (2001)- Chemistry (Calcutta University)
Ph.D. (2008)- Cell & Molecular biology; Bose Institute (affiliated to Jadavpur University)
Fellowships and Awards (in chronological order)
1999- Somnath Mukherjee Memorial Award by Ramakrishna Math & Mission for securing first class in graduation
2001- Qualified NET (Lecturership) in Chemical Science; jointly organized by CSIR and UGC
2002- Qualified GATE in Chemistry; organized by MHRD, Govt. of India,
2008- Qualified for the Research Associate fellowship from (CSIR), Govt. of India
2010- “Up on the Roof” Post-doctoral fellowship from the Human Cancer Genetics Program and the Comprehensive Cancer Center of the Ohio State University, Columbus, OH, USA
2012- Distinguished Undergraduate Research Mentor Award Nominee, The Ohio State University
2016- ‘Ramalingaswami re-entry fellowship’ by Department of Biotechnology (DBT)
2024- Guest editor for the Special Method collection on Centrosome and cilia biology, JoVE
My childhood aspiration to be a chemistry teacher evolved in a new direction when I finished M.Sc. in chemistry, and started doing simple biochemical or biophysical experiments in Dr. Lohia’s lab at Bose Institute. I realized how bored I was during my masters due to overburdening of knowledge of theoretical chemistry, and lack of any realistic orientation of that knowledge other than practical classes in conventional education system. I started enjoying reading papers or reference books, learning molecular and cell biology, and most importantly, doing experiments on my own. I could utilize my little knowledge of chemistry in troubleshooting problems in molecular/cell biology or protein chemistry. I enjoyed the fun of science and also learned to face the failures. The PhD tenure helped me to gain confidence to take on challenges of professional life.
My interest to explore cell cycle regulation in mammalian cells took me to the laboratory of Dr. Harold Fisk at the Ohio State University. Harold’s lab environment strongly encourages independent scientific thoughts and questions among students, scholars and post-docs. His guidance helped me to grow mature as an independent researcher in preparing data presentation, proposals, manuscripts, teaching modules and mentoring students in lab/classes. My tenure as a cell biologist taught me that success may not always be publishing in ‘one word’ journals or translating the research to benchside, but to prepare the avenue for those while looking passionately at the cells and planning how to see them more vividly. During 2015, I tested the sheer uncertainty in my career, when Prof. Anita Hopper, an eminent tRNA biologist in the Ohio State Unversity rescued me. Anita’s life is an inspiration to others, while she is an example of super-dynamic but organized and disciplened PI, and also a motherly figure to almost any student/researcher/scientist known to her. Spending one year in her lab was a gift to me. My expertise in cell biology was utilized in an independent manner, while I was carefully taught RNA biochemistry and yeast genetics by her lab. I learnt the lesion from her to consider ‘life beyond science’ is as valuable as one’s passion for science.
Later, I had moved to the department of Radiation Oncology, and worked as research scientist in Dr. Monica Venere’s lab that is focused to identify novel therapeutic intervention for glioblastoma, the high grade brain tumor in human, by combining cell cycle regulatory pathways and radiation therapies. During my stay in USA I realized that the advancement of science needs intense contribution from people of different level, and from various parts of the world but in an explicit language of science. Therefore, when I received the prestigious ‘Ramalingaswami re-entry fellowship’ I did not wait to come back and join the life sciences department of Presidency University that carries the legacy of contributing to socio-economic evolution beyond Kolkata, Bengal or India. Expectedly, the vibrant and resourceful atmosphere of the department, talented and motivated pool of students, multi-disciplinary expertise of the faculty, and encouragements from my seniors helped me to establish my own research group here. I wish to bring the training experiences in my way to function as an independent scientist and an interactive teacher in Presidency University.
Independent research (June, 2017-present): Department of Life Sciences, Presidency University
Project- Molecular regulation of ciliogenesis and centriole assembly in mammalian cells.
Post-doctoral research (Aug, 2016- June, 2017): Department of Radiation Oncology, James Cancer Hospital and Comprehensive Cancer Center, The Ohio State University Wexner School of Medicine, Columbus, Ohio, USA; PI- Dr Monica Venere, Assistant Professor
Project- Characterizing primary cilia mediated signaling in cancer stem cells of glioblastoma.
I studied if primary cilia mediated signals regulate the stem-ness and/or affect the invasiveness of the cancer stem-like cell (CSC) population in glioblastoma, and if KIF11 (or Eg5), the mitotic kinesin that drives proliferation and self-renewal in glioblastoma, regulates primary cilia assembly and/or maintenance in CSCs. I have also studied if some specific post-translational modifications (PTM, in this case acetylation) at certain residues of KIF11 may modulate its role in these GBM-derived CSCs, compared to that in Non-CSC pools of cells.
Post-doctoral research (July, 2015- Aug, 2016): Department of Molecular Genetics, Ohio State University, USA; PI- Dr Anita Hopper, Professor
Project- Characterizing novel tRNA nuclear export pathway(s) using Saccharomyces cerevisiae
In addition to export from nucleus to cytoplasm, mature tRNAs also move from the cytoplasm to the nucleus via retrograde tRNA nuclear import, a process that is conserved from yeast to vertebrates and is crucial in tRNA quality control, particularly to monitor processing of 5’ and 3’ ends and various modification states of nucleotides in tRNAs. I studied the differential activity of yeast exportin-t homolog Los1, and the newly identified alternative export modules that are Mex67/Mtr2, to efficiently export tRNA in normal and stressed condition and also to maintain tRNA quality control in S. cerevisiae. My data suggested that the primary nuclear export mediated by Los1p is most efficient, while the alternative pathways are error-prone in maintaining the quality control of tRNA in yeast.
Post-doctoral research (Dec, 2008- June, 2015): Department of Molecular Genetics, Ohio State University, USA; PI- Dr Harold Fisk, Associate Professor
Principal project- Regulation of centrosome duplication and ciliogenesis in human.
I identified centrosome- associated pool of Voltage Dependent Anion Channel proteins (VDACs), best known as mitochondrial outer membrane porins that regulate bioenergetics. Of three human VDACs, VDAC1 and VDAC3 negatively regulate ciliogenesis through non-redundant pathways, while VDAC2 supports early stages of cilia assembly. Also, VDAC3 binds Mps1 kinase, a spindle assembly checkpoint protein and an important regulator of centrosome assembly, and recruits Mps1 to centrosomes. Thereby, VDAC3 regulates Mps1-mediated centrosome assembly and centriole reduplication during prolonged S- phase. The activity of Mps1 is centriole assembly is imparted through phosphorylation of Centrin2, and this activity of is inhibited by Centrin3, two bona fide centriolar proteins. Mps1 also regulates cilia disassembly during cell cycle re-entry.
Post-doctoral research (Aug, 2008- Nov, 2008): Department of Biochemistry, Bose Institute, India; PI- Prof. Anuradha Lohia
Project: Characterization of formin homology proteins in Entamoeba histolytica.
Among the eight formins in E. histolytica genome, there were four formins- EhFormin5-8 are distinct from other eukaryotic formins. During the brief tenure, I generated constructs for expressing these four unique formins with a multi-affinity HH-tag (HA epitope, 6X-Histidine) in E. histolytica cells, in order to identify novel functions of these formins.
Doctoral Research (Dec, 2001- July, 2008): Department of Biochemistry, Bose Institute, India; Supervisor- Prof. Anuradha Lohia
Thesis title: Molecular analysis of genes regulating cell division in Entamoeba histolytica.
Entamoeba histolytica is a human parasite causing amoebiasis and dysentery in humans. Utilizing functional genomics tools, we identified eight formin homology proteins in E. histolytica. Formins are best known to regulate actin cytoskeletal rearrangement, which is critical for amoeba cells’s motility and pathogeneicity. We showed that EhFormin1 and EhFormin2, the two diaphanous-related formins of E. histolytica regulate the acto-myosin cytoskeleton remodeling during motility, phagocytosis and cell division in these cells. EhRho1, the amoeba homolog of mammalian RhoA small GTPase, binds EhFormin1 and EhFormin2 and regulates their activity in controlling actin remodeling. EhRho1 is modified and inactivated by bacterial glucosylating toxins, although the holotoxins cannot enter, and therefore cannot intoxicate Entamoeba cells. A significant fraction of axenically growing E. histolytica cells contains two or more nuclei, while the nuclear DNA content shows remarkable variation suggesting lack of strict regulations in cell cycle events in these cells. We showed that nuclear division cycle is uncoupled from cell division in these cells, and the later is often irregular, and may need midwifery assistance. My research, for the first time, identified bipolar but atypical microtubular spindles that were segregating amoeba genome. Interestingly, several Entamoeba cells undergo mitosis on multi-polar spindles, suggesting that multipolar mitosis and erratic cell division may lead to the observed heterogeneity in cellular genome content in Entamoeba histolytica.
Teaching philosophy
I am passionate about teaching, and always enjoyed whenever I got opportunity, may that be a theory class, or mentoring students in research lab. However, I wish to appropriately share my time between teaching and research, and to establish myself as an an independent scientist and interactive teacher. I have learnt a lot about teaching from my post-doc mentors Dr. H. Fisk and Dr. A. Hopper of the Ohio State University, and from iBiology, a platform to spread biology education (www.ibiology.org). I wish to teach in a way that excites the students, and involves their thinking skills instead of memorization. I want to encourage students about the fascinating aspects of biomedical sciences, but also to suggest them for various career paths instead conventional routes.
Teaching experiences
I teach few modules of MSc in Biotechnology and Molecular Microbiology courses and PhD coursework (Principles of chemistry, Cell biology, Biophysical techniques, Research proposal/grant preparation etc) at the Institute of Health Sciences, PU [erstwhile School of Biotechnology].
Previous teaching experiences (chronological order)
Presidency University:
Cell cycle, Differentiation, and Oncogenesis [PG-2019]; Research proposal/grant preparation [2019-21]
Dept of Life Sciences:
Thermodynamics and kinetics in biological problems, Cell biology of Cytoskeleton [UG-2018]; Principles of physical and general chemistry (Thermodynamics, chemical equilibrium, Chemical bonding and molecular structure’, chromatography techniques) [UG-2018, 2019]; Cytoskeleton and motor proteins, Ciliogenesis, and Hedgehog signaling in Developmental biology [PG-2018, 2019]; Research proposal/grant preparation [2019]
Dept of Chemistry:
Colloids and macromolecules, Chemical equilibrium [UG-2018]; Techniques to study structure and function of biomolecules [PG-2018, 2019]
Ohio State University:
1. Spring semesters (2013 and 2014): Oral lecture on ‘Fluorescence microscopy in cell biology’ followed hands on training; senior undergraduate (UG) course ‘Eukaryotic Cell and Developmental Biology’, Molgen5602, The Ohio State University.
2. Fall semester-2014: Oral lectures on ‘Centrosome assembly and ciliogenesis’, as part of the undergraduate theory course- Cell Biology, Molgen5607, The Ohio State University.
Other professional experiences
Coordinator- Departmental seminars & Colloquium, Dept. Life Sciences, Presidency University (Aug, 2017-Aug, 2019)
Member- Various departmental committees of Dept of Life Sciences and School of Biotechnology, Presidency University
Organizer- Member of the Organizing committee, Regional Young Investigators Meeting, Kolkata, 2019
Ad hoc Reviewer- Journal of Visualized Experiments, OncoTargets and Therapy
Judge: Denman Undergraduate Research Poster competition, The Ohio State University
My research group ‘CellBioLab' is an expanding group that closely functions with the research group ‘RNABioLab’ of Dr. Chandrama Mukherjee, through sharing facilities and resources. The members of ‘CellBioLab' are-
Present members-
1. Shrabani Halder CSIR- SRF July, 2019- present
2. Arpita Dutta DBT- SRF (previously project JRF) Feb, 2020- present
3. Priyanka Das UGC- SRF Feb, 2021- present
4. Priyadarshini Halder UGC- JRF Oct, 2021- present
Lab alumni-
Research/Project Assistants-
1. Rajat Saha (Dec, 2017- May, 2019; Currently- Teacher, Special School at Purulia)
2. Ruchira Ghosh (July, 2019- Nov, 2019)
3. Shaitali Laha Roy (Nov, 2019- June, 2021; Currently- Research scholar, IIT Bombay)
4. Rupsa Mondal (Aug, 2022- Jan, 2023)
M.Sc. Dissertation students-
1. Nafis Al Rubai 2018-19 M.Sc. in Life sc. (Currently- Business)
2. Shilpa Khatun 2019-20 M.Sc. in Life sc. (Currently- Teacher, Al Ameen Mission)
3. Priyadarshini Halder 2019-20 M.Sc. in Life sciences (Currently- pursuing PhD at IHS, PU)
4. Aranya Mitra 2020-21 MSc. in Microbial biotechnology School of Biotechnology (currently- Pursuing PhD at The Hebrew University of Jerusalem, Israel)
5. Rahit Dewanji 2021-22 MSc in Biotechnology, IHS (erstwhile SBT)
(currently- Pursuing PhD at University of Nebraska, USA)
5. Rupsa Mondal 2021-22 MSc in Biotechnology, IHS (erstwhile SBT)
6. Saheli Dhar 2023-24 MSc in Molecular Microbiology, IHS
7. Bidisha Mukherjee 2023-24 MSc in Molecular Microbiology, IHS
Short term/Summer trainees
2024- Biprodip (Rahara RK Mission Centenary College), Arpan (Haldia Institute of Technology)
2023- Ahiri (Amity University), Adwaita (St. Xaviers University; Currently pursuing PhD at the University of New Hampshire, USA)
2022: Anushka (St. Xaviers College, Kolkata), Subhadip (Rahara RK Mission College, pursuing MSc at IISc Bangalore), Tiyasa (Siv Nadar University-pursuing PhD at the University of Maine, USA)
2019: Avirup (Amity Univ., Kolkata), Sunanda (SRM Univ.), Subhadip and Sanchita (Adamas Univ)
2018: Abir-ul, Sahil, Ritwik, Deblina (PU DLS), Tofayel (PU Chem), Snehasish (TNU)
UG trainees (DLS, Presidency University)
1. Late Ratul Das (DLS_UG of 2017-20)
2. Biyas Mukherjee (2017-20; currently- PhD scholar at SINP, after MSc. in Life Sc. from PU)
3. Asmita Dutta (2017-20; currently- PhD scholar at IISc after MSc. in Biotech. from RGCB, Kerala)
Mentoring UG students (DLS, Presidency University)
2020-2021: Sudarshan (currently- iPhD at IIT Hyderabad), Pratistha (iPhD at IACS-IIT Kharagpur; Currently pursuing PhD at the Virginia Tech, Blacksburg, USA)
2021-2022: Shristi (currently- MSc in biotechnology, IIT Mumbai; selected as Khorana international exchange scholar), Shirsadri (iPhD at IISc)
2010- 2020 Member of American Society for Cell Biology
2011-2013 Member of American Heart Association
2019- present Life member of Indian Society of Cell Biology
2023- present Member of Ciliopathy consortium, India
Peer Reviewed Publications (in reverse chronological order) (* corresponding author)
Gayen A., Mukherjee A., Kumar K., Majumder S, Chakrabarti S, 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. Experimental Cell Research 429(2):113671.
Halder P., Khatun S., and Majumder S.* (2020) Freeing the brake: Proliferation needs the primary cilium to disassemble. Journal of Biosciences 45: 117
Zalenski A.A., Majumder S., De K., Venere M. (2020) An interphase pool of KIF11 localizes at the basal bodies of primary cilia and a reduction in KIF11 expression alters cilia dynamics. Scientific Reports 10(1):13946.
De K., Grubb T., Zalenski A.A.., Pfaff K., Pal D., Majumder S., Summers M.K., Venere M. (2019) Hyperphosphorylation of CDH1 in glioblastoma cancer stem cells attenuates APC/CCDH1 activity and pharmacological inhibition of APC/C CDH1/CDC20 compromises viability. Molecular Cancer Research 17(7):1519-1530.
Chatterjee K., Majumder S., Wan Y., Shah V., Wu J., Huang H-Y., and Hopper A.K. (2017) Sharing the load: Mex67-Mtr2 co-functions with Los1 in primary tRNA nuclear export. Genes and Development. 31: 2186-2198.
Sawant D.B., Majumder S., Yang C-H., Eyers P.A., and Fisk H.A. (2015) Centrin 3 is an inhibitor of centrosomal Mps1 and antagonizes Centrin 2 function. Molecular Biology of the Cell. 26 (21): 3741-53. (Highlighted article of the month Nov, 2015)
Majumder S., Cash A., and Fisk H.A. (2015) Non-overlapping distributions and functions of the VDAC family in ciliogenesis. Cells. 4(3): 331-353.
Majumder S.*, and Fisk H.A. Quantitative immunofluorescence assay to measure the variation in protein levels at centrosomes. (2014) Journal of Visualized Experiments (94); e52030
Majumder S., and Fisk H.A. VDAC3 and Mps1 negatively regulate ciliogenesis. (2013) Cell Cycle. 12 (5): 849-58.
Majumder S., Slabodnick M, Pike A, Marquardt J, and Fisk H.A. (2012) VDAC3 regulates centriole assembly by targeting Mps1 to centrosomes. Cell Cycle. 11 (19): 3666-78.
Liu C, van Dyk D, Choe V, Yan J, Majumder S., Costanzo M, Bao X, Boone C, Huo K, Winey M, Fisk H, Andrews B, Rao H. (2011) Ubiquitin ligase Ufd2 is required for efficient degradation of Mps1 kinase. Journal of Biological Chemistry, 286 (51): 43660-7.
Yang C-H., Kasbek C., Majumder S., Yusof A.M., and Fisk H.A. (2010) Mps1 phosphorylation sites regulate the function of Centrin 2 in centriole assembly. Molecular Biology of the Cell, 21 (24): 4361-72.
Mukherjee C#., Majumder S.#, and Lohia A. Inter-cellular variation in DNA content of Entamoeba histolytica originates from temporal and spatial uncoupling of cytokinesis from the nuclear cycle. (2009) PLoS Neglected Tropical Disease, 3(4): e409. (# equal contribution) (Image selected for ‘Cover Photo’), The article is selected for discussion in the Editor’s Choice section, Science, 324(5931): 1119.
Majumder S., and Lohia A. Entamoeba histolytica encodes unique formins, a subset of which regulates DNA content and cell division. (2008) Infection and Immunity, 76: 2368-2378.
Ghosh Dastider P., Majumder S., and Lohia A. (2007) Eh Klp5 is a divergent member of the kinesin 5 family that regulates genome content and microtubular assembly in Entamoeba histolytica. Cellular Microbiology, 9; 316-328.
Majumder S., Schmidt G., Lohia A., and Aktories K. (2006) Eh Rho1, a RhoA-like GTPase of Entamoeba histolytica is modified by clostridial glucosylating cytotoxins. Applied and Environmental Microbiology, 72; 7842-7848.
Other publications
1. 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 and International Health. 12: 30-31. (Brief report)
2. 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. (Invited review)
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