Profile

Research

Publications

Team

Alumni

Rashmi Mishra, PhD

Scientist EI

+91-471-2529593

rashmimishra@rgcb.res.in

RASHMI-1
  • Profile

    • PhD degree in Neuroscience from the National Brain Research Centre, Manesar, India
    • Masters' in Medical Biotechnology from the All India Institute of Medical Sciences, New Delhi
    • 2016 - till date Scientist EI, Rajiv Gandhi Centre for Biotechnology, Trivandrum, India
    • 2012-2016, DBT-Ramalingaswami Fellow and Scientist C at Rajiv Gandhi Centre for Biotechnology, Trivendrum, India
    • 2008-2011, Postdoctoral fellow at Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany and Curie Institut, Paris, France
    • 2003-2004, Visiting Fellow, Tufts University School of Medicine, Boston, USA
    • 2012 : Selected for DBT-Rapid Grant for Young Investigator Award (RGYI)
    • 2012-2017: Department of Biotechnology, Ramalingaswami fellowship award
    • 2008-2010: Max Planck Institute post-doctoral fellowship
    • 2008: Center for Developmental Biology, RIKEN, Japan, travel fellowship for ‘Turning Neurons to Brain’ conference.
    • 2001: Council for Scientific Research, Govt. of India, Junior and Senior Research fellowship (CSIR-NET) for pursuing PhD degree.
    • 2003-2004: Visiting Fellow (funded by FIRCA-NIH, USA), Tufts University School of Medicine, Boston, USA
    • 2003: First Rank in Pre-PhD Neuroscience Course work
    • 2001: Indian Institute of Technology, India (IIT, Graduate Aptitude Test in Engineering) 82 percentile
    • 1998-2000: Dept of Biotechnology, Govt. of India fellowship for pursuing Masters’ in Medical Biotechnology
    • 1997: Delhi University Merit Medal for first position in Bachelors degree with Honors.
  • Research

    MAJOR THEME OF THE LAB: MECHANOBIOLOGY OF DISEASE DEVELOPMENT, PROGRESSION AND THERAPEUTICS

    Overview: Brain sciences and brain associated diseases are now being pursued with more cross-disciplinary approaches at the interface of understanding the plasma membrane resident modules, their communication with the micro and macroenvironments and the net consequences of such interactions on cellular functioning. In this context, the two principles that we have recognized to be crucial to brain pathophysiology are the clustering induced biomechanical force alterations of surface membranes and the assembly/disassembly kinetics of lipid rafts modules.

    Hence, the major focus of the lab is to understand the link between the 'Lipid Rafts and Biomechanical Force Homeostasis in Brain Physiology and Pathologies'. Under this research theme two broad pursuits are directed towards: (i) Understanding the role of lipid rafts in biophysical forces homeostasis of brain cancers, and how to hijack force homeostatic machineries to reverse/cure pathologies and (ii) How 'Galectins'-the major lipid raft organizers and surface mechanical force generators (due to glycan mediated surface clustering effects) impacts central nervous system development and pathologies. The PI directly works and co-ordinates both the projects along with the lab colleagues.

    Theme 1 Sub-projects:

    1.1 Targeting Tumor Cell Biomechanical Homeostasis For Novel Anti-GBM (Glioblastoma multiforme) Therapeutics

    Glioblastoma multiforme is a highly complex, aggressive and deadly brain tumor. The rapidly expanding GBM tumor heterogeneity and recurrence, chemo and radio-resistance, oncogenic mutations, alternative splice variants, gene polymorphism and rapid chromatin remodelling has posed enormous difficulties in identifying the specific cellular targets.

    The lead emerging concept at the frontiers of oncology is that the tumor cells maintain a very subtle balance of biomechanical forces such as the shear forces from the blood vessels, rigidity stresses from the stiffened extracellular matrix and glycocalyx clustering as well as the hydrostatic forces from the interstitial fluid accumulation.

    The base idea therefore is to learn 'how' to misbalance the delicate force homeostasis to enable tumor cell death. Understanding of such principles will generate novel diagnostic and therapeutic regimes that will surpass the current complications encountered due to tumor heterogeneity

    Hence, our working hypothesis is that by better understanding the reciprocal mechanism between the cancer microenvironmental force generating agents and tumor mechanoadaptive circuitries, we may be in a position to hijack the hub molecular players which 'turn' tumor cells vulnerable to cell death. A 'target based' approach coupled with phenotypic screens that alter the physico-chemical characteristics of cancer cells, is therefore proposed in this research study for anti-GBM cancer drug discovery efforts.

    1.2  Biophysical forces in stem cell dynamics and tumorigenesis

    Upcoming reports suggest that imbalances of biophysical forces on stem and progenitor cells in different organ systems may be one of the primary causative agent for the loss of proliferation control and transformation into tumor cells. However, an understanding of the principles underlying the processes of normal and pathogenic mechanosensing and mechanotransduction is at a very preliminary stage. We are concentrating on the plasma membrane resident modules called lipid rafts and its specialized form, the caveolae to trace the stem cell mechanocircuitries at different thresholds of rigidity and shear forces.

    Theme 2 Sub-projects:

    2.1. Galectins in tumorigenesis 

    Galectins are recently being implicated to play crucial roles as both pro- and anti tumorigenic factors, however the precise mechanistic insights into their roles in generating tumor heterogeneity is missing. We find that several galectins are expressed simultaneously in any tumor and their combinatorial concentration levels may be crucial to the net outcome of the tumor fate. We are now trying to dissect the mechanism of action of galectins in tumorigenesis via an interdisciplinary approach involving surface mechanical remodelling principles.

    2.2. Galectins in CNS Morphogenesis 

    Galectins is a family of beta-galactoside binding and non-classically secreted proteins that was initially identified in the process of axon pathfinding. Even though galectins’ roles are now being established in several brain disorders such as in neuroblastoma and glioblastomas, dengue fever, ischemia, autism, multiple sclerosis and experimental allergic encephalomyelitis (EAE) etc., ironically, 'no systematic studies' have been performed on its expression, regulation and functions in brain's normal physiology. We have analyzed the in situ hybridization data from mouse and microarray data from human brain and have now validated the transcript expression with the protein expression. Results show that galectins' are expressed in both mouse and human brain but in a spatially heterogeneous pattern that may contribute to differential brain functions. In addition, we have identified galectins to be crucial targets of brain enriched transcription factors and further neuroinformatics analysis has predicted galectins to be functionally relevant in several brain processes such as neurogenesis, gliogenesis, cell proliferation, stem cell maintenance and differentiation, neurite extension, axonal growth, synaptogenesis and synaptic transmission. We are now dissecting the roles of each galectin in distinct brain functions and preliminary results suggests that galectins maybe intricately involved in presenting a regulative logic to brain architecture and functions.

    The major highlights of the work so far that 1) Galectins have a highly heterogeneous transcript expression within and across mouse and human brain anatomical locations. 2) Galectins are predicted crucial targets of brain enriched transcription factors. 3) Galectin-1,-3,-8 and -9 may regulate several neuronal processes, while galectins-2,4,6,7 and 12 may regulate more specialized and localized functions. 4) Galectins-8 is most conserved across mouse and human brain. 5) Due to diverse regional distribution within and across species, may be considered as novel signatures of brain heterogeneity and functions.

    1. Rapid Grant for Young Investigator,Department of Biotechnology, 2013-2016
    2. Ramalingaswami Fellowship,Department of Biotechnology, 2012-2017
    3. Neuro TaskForce Grant,Department of Biotechnology, 2012-2016

    Potential Postdocs: Our lab can consider postdocs via DBT Wellcome Early Career Award, Women Scientist Schemes of DST, DST-SERB Postdoctoral scheme, DBT-Biocare Scheme, DBT Postdoctoral schemes, UGC-Faculty Recharge program etc. Interested candidates please send an email to rashmimishra@rgcb.res.in in including CV and a statement of purpose on why you are interested in the lab.

    Graduate Students: Our lab accepts PhD candidates through RGCB Ph.D. Program.

    JRF/Project Assistants: Watch out for advertisements from time to time.

    Summer Students and Trainees: Applications are considered throughout the year.

  • Publications

    MAJOR THEME OF THE LAB: MECHANOBIOLOGY OF DISEASE DEVELOPMENT, PROGRESSION AND THERAPEUTICS

    A. Broad Theme: Hijacking the mechanical homeostasis of pathologies to enable better disease management

    1. Bacoside A induces tumor cell death in human glioblastoma cell lines through catastrophic macropinocytosis (2017). Sebastian John, KC Sivakumar and Rashmi Mishra* (*corresponding author). Frontiers in Molecular Neuroscience, 10:171, pages 1-22. doi: 10.3389/fnmol.2017
    2. Extracellular proton concentrations impacts LN229 glioblastoma tumor cell fate via differential modulation of surface lipids (2017). Sebastian John, KC Sivakumar and Rashmi Mishra* (*corresponding author). Frontiers in Oncology, 7:2, pages 1-23.  doi: 10.3389/fonc.2017.00020

    B. Broad Theme: Elucidation of the role of galectins in the mechanical homeostasis of pathologies and organ morphogenesis.

    1. mRNA transcriptomics of galectins unveils heterogenous organisation in mouse and human brain (2016). Sebastian John and Rashmi Mishra*(*corresponding author). Frontiers in Molecular Neuroscience, 9:139, pages 1-23. doi: 10.3389/fnmol.2016.00139
    2. Galectin-9: From cell biology to complex disease dynamics (2016).  Sebastian John and Rashmi Mishra* (*corresponding author). Journal of Bioscience, Sep;41(3), pages 507-34. DOI: 10.1007/s12038-016-9616-y
    3. Galectin-9 trafficking regulates apical-basal polarity in Madin Darby Canine Kidney epithelial cells (2010). Rashmi Mishra, M Gryzbek, Nishi T and Kai Simons. Proceedings of National Academy of Sciences, USA. Oct12;107(41):17633-8. doi: 10.1073/pnas.1012424107 (Highlighted in F1000)
    4. Determination of the carbohydrate binding preference of human galectins with carbohydrate microaarays (2009). Hotlacher T, Oberli MA, Werz DB, Bufali S, Stocker B, Rashmi Mishra, Kai Simons, Hirashima M, Niki T, Seeberger PH. ChemBioChem, Jul 26;11(11):1563-73. doi: 10.1002/cbic.201000020

    C.  Broad Theme: Elucidation of the role of lipid rafts associated modules in Central Nervous System development, mechanical homeostasis and diseases.

    1. GAP-43 is essential for the neurotrophic effects of BDNF and positive AMPA receptor modulator S18986 (2009). SK Gupta*, Rashmi Mishra*, S Kusum, M Spedding, Karina Meiri, Pierre Gressens and Shyamala Mani. (*equal contribution). Cell Death and Differentiation, Apr;16(4):624-37. doi: 10.1038/cdd.2008.188
    2. Both cell autonomous and cell non-autonomous functions of GAP-43 are required for normal patterning of the cerebellum in vivo (2008). Y Shen*, Rashmi Mishra*, Shyamala Mani and Karina F Meiri (* equal contribution). Cerebellum, 7(3):451-66. doi: 10.1007/s12311-008-0049-5
    3. Addressing the role of extrinsic cues in neuronal polarization. SK Gupta, Rashmi Mishra, Karina Meiri and Shyamala Mani (2008). Developmental Biology 319(2):502-502. DOI: 10.1016/j.ydbio.2008.05.124
    4. GAP-43 is a key to mitotic spindle control and centrosome-based polarisation in neurons (2008). Rashmi Mishra, SK Gupta, Karina Meiri, M Fong, P Thorstrup, D Junker and Shyamala Mani. Cell Cycle, Feb 1;7(3):348-57

      Listen to Dr. Mishra's postdoctoral work from Prof. Kai Simons (the membrane master) at:

      https://www.ibiology.org/cell-biology/lipid-rafts/#part-3

  • Team


    Rashmi Mishra (Principal Investigator)

    I received my PhD from the National Brain Research Centre, Manesar where I worked in the Developmental Neuroscience and Stem Cell laboratory of Dr. Shyamala Mani. Following this, I joined Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany in Prof. Kai Simons Lab. Here, I began addressing the principles underlying lipid-protein-glycan assemblies in membrane organization that paved way to my current focus on the biophysical and biochemical membrane organizing principles underlying physiological and pathological conditions. I love watching discovery channel on wild-life, catching up on neuroscience news, and reading about ayurveda, the holy texts, lives of historians, scientists and leaders. My favourite saying is ‘Be like a rubber ball, the harder it is hit, the higher it bounces’. Email to: rashmimishra@rgcb.res.in; r.mishra2007@gmail.com

    SAM
    SAM

    Rashmi Mishra (Principal Investigator)

    I received my PhD from the National Brain Research Centre, Manesar where I worked in the Developmental Neuroscience and Stem Cell laboratory of Dr. Shyamala Mani. Following this, I joined Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany in Prof. Kai Simons Lab. Here, I began addressing the principles underlying lipid-protein-glycan assemblies in membrane organization that paved way to my current focus on the biophysical and biochemical membrane organizing principles underlying physiological and pathological conditions. I love watching discovery channel on wild-life, catching up on neuroscience news, and reading about ayurveda, the holy texts, lives of historians, scientists and leaders. My favourite saying is ‘Be like a rubber ball, the harder it is hit, the higher it bounces’. Email to: rashmimishra@rgcb.res.in; r.mishra2007@gmail.com

    Sebastian John (PhD student, ICMR SRF)

    I come from Biochemistry background and did my Bachelor's from St. Joseph’s College, Bangalore and Master's from St. Berchman’s College, Changanassery. I have received ICMR SRFship. At RGCB, I am working at the interface of biochemistry and the highly interdisciplinary field of Mechanobiology. My major focus is on understanding biophysical non-homeostasis in stem cell proliferation as the primary cause of the origin of brain cancers. I like travelling and listening to music. My favourite saying is ‘Let your work speak for you’. Email to: sebastianjohn@rgcb.res.in

    SAM
    SAM

    Sebastian John (PhD student, ICMR SRF)

    I come from Biochemistry background and did my Bachelor's from St. Joseph’s College, Bangalore and Master's from St. Berchman’s College, Changanassery. I have received ICMR SRFship. At RGCB, I am working at the interface of biochemistry and the highly interdisciplinary field of Mechanobiology. My major focus is on understanding biophysical non-homeostasis in stem cell proliferation as the primary cause of the origin of brain cancers. I like travelling and listening to music. My favourite saying is ‘Let your work speak for you’. Email to: sebastianjohn@rgcb.res.in

    Gayathri KG (PhD student, UGC JRF)

    I come from Botany background and did my Bachelor from Maharaja’s College, Ernakulam and Masters from St. Joseph’s College, Trichy. I have qualified Inspire, CSIR-JRF NET and UGC-JRF NET fellowships eligibility. At RGCB, I took the challenge to move from basic science to work in a highly interdisciplinary and cutting edge field of mechanobiology. The field inspires me to explore novel strategies towards disease therapeutics based on disturbing the mechanical homeostasis of cancer niches. When not in lab, I can be found playing violin or reading books. I love spending time with family and friends. Email to: gayathrikg@rgcb.res.in

    Gayathri KG (PhD student, UGC JRF)

    I come from Botany background and did my Bachelor from Maharaja’s College, Ernakulam and Masters from St. Joseph’s College, Trichy. I have qualified Inspire, CSIR-JRF NET and UGC-JRF NET fellowships eligibility. At RGCB, I took the challenge to move from basic science to work in a highly interdisciplinary and cutting edge field of mechanobiology. The field inspires me to explore novel strategies towards disease therapeutics based on disturbing the mechanical homeostasis of cancer niches. When not in lab, I can be found playing violin or reading books. I love spending time with family and friends. Email to: gayathrikg@rgcb.res.in

    Meera R Nair (Technical Officer and Lab Manager)

    I am essentially from Computational Science and learnt all of biology at RGCB. I find it really intriguing to learn brain anatomy. I assist the PI and students in general lab affairs and experiments. I like exercising, music and food. Catching up with family brings in me the special delight of life. My favourite saying is ‘Be the change you want to see’. Email to: meerar@rgcb.res.in

    Meera R Nair (Technical Officer and Lab Manager)

    I am essentially from Computational Science and learnt all of biology at RGCB. I find it really intriguing to learn brain anatomy. I assist the PI and students in general lab affairs and experiments. I like exercising, music and food. Catching up with family brings in me the special delight of life. My favourite saying is ‘Be the change you want to see’. Email to: meerar@rgcb.res.in

    Current Interns/Trainees

    Anju Gayathri, Sharika, Poornima, Priyadharsini Sukumaran, Priyadarshini S.

    Current Interns/Trainees

    Anju Gayathri, Sharika, Poornima, Priyadharsini Sukumaran, Priyadarshini S.

  • Alumni


    Past Trainees/Summer Interns/Project Assistants/JRFs

    Archana R, Aiswaria Lekshmi, Gayathri Ashok, Sethu Parvathy Pillai, Delvin Pauly, Thasni Rabia, Siji S, Drishya Nair, Shareena Kamal, Sneha N Kannu

    Past Trainees/Summer Interns/Project Assistants/JRFs

    Archana R, Aiswaria Lekshmi, Gayathri Ashok, Sethu Parvathy Pillai, Delvin Pauly, Thasni Rabia, Siji S, Drishya Nair, Shareena Kamal, Sneha N Kannu