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University of Exeter Medical School

Dr Akshay Bhinge

Dr Akshay Bhinge

Senior Lecturer in Clinical & Biomedical Science

 A.Bhinge@exeter.ac.uk

 7459

 +44 (0)1392 727459

 Living Systems Institute T02.16

 

Living Systems Institute, University of Exeter, Stocker Road, Exeter, EX4 4QD


Overview

Biography

Dr. Akshay Bhinge obtained his degree in Clinical Medicine and Surgery (M.B.B.S.) from Grant Medical College, Mumbai, India and his Masters in Biomedical Engineering (M. Tech) from the Indian Institute of Technology, Mumbai, India. He joined Dr. Vishwanath Iyer's lab at the University of Texas at Austin, USA for his doctoral work graduating with a Ph.D. in 2009. His doctoral thesis focused on identifying downstream targets of oncogenic transcription factors and microRNAs in human primary and cancer cell lines by developing novel genomics tools based on next-generation sequencing technologies. In 2010, he joined Dr. Lawrence Stanton's group as a postdoctoral fellow at the Genome Institute of Singapore. His postdoctoral work focused on modelling human neurodevelopment and neurodegeneration using pluripotent stem cells. Using patient-derived induced pluripotent stem cells (iPSC), his research uncovered a role of the ERK pathway in driving motor neuron loss in Amyotrophic Lateral Sclerosis (ALS). He joined the LSI as a Research Fellow in 2017 to setup his own group. His research is aimed at developing complex human models of the nervous system to understand motor neuron diseases. A deeper molecular understanding of these neurodegenerative diseases will help in development of future therapies aimed at halting or even reversing the relentless neuronal loss.

Qualifications

•  Doctor of Philosophy (Ph.D.): Cell and Molecular Biology, University of Texas at Austin, Texas, USA
•  Master of Technology (M.Tech.): Biomedical Engineering, Indian Institute of Technology-Bombay,  India
•  Bachelor of Medicine, Bachelor of Surgery (M.B.B.S.): Clinical Medicine and Clinical Surgery, Grant Medical College and Sir JJ group of Hospitals, Mumbai, India

Bhinge Lab website

Research keywords

  • induced Pluripotent Stem Cells (iPSC)
  • Motor Neuron Disease (Amyotrophic lateral Sclerosis)
  • Frontotemporal Dementia (FTD)
  • Disease modelling in a dish
  • Neurodegeneration
  • 3D models of brain and spinal cord
  • ChIP-sequencing
  • Single cell RNA-sequencing
  • Enhancers
  • MicroRNAs
  • RNA binding proteins
  • Regulatory networks
  • Bioinformatics

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Research

Research interests

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative condition characterized by selective loss of motor neurons i.e. neurons that convey signals from the brain and spinal cord to the muscles. ALS patients display progressive loss of motor neurons, suffer increasing immobility with paralysis, and eventually die from failure of the respiratory muscles. Although there are a few drugs in clinical trials, currently there is no cure to halt or reverse the degeneration. Understanding the molecular events that lead to selective motor neuron degeneration in ALS is paramount in developing therapies to halt or even reverse the degeneration. The lab uses patient-derived and CRISPR-edited pluripotent stem cells to develop human models of neuronal ageing and ALS in vitro. These models are further investigated using a combination of single-cell RNA-Seq, epigenomics and genetic screens including RNAi and CRISPRa. The goal is to uncover disruptions in the transcriptional and non-coding RNA networks that lead to disease, in order to develop therapies aimed at halting the relentless neurodegeneration.

Selected Publications

J Ganssauge, S Hawkins, S C Namboori, S Leung, J Mill, A Bhinge. Rapid and Inducible Mislocalization of Endogenous TDP43 in a Novel Human Model of Amyotrophic Lateral Sclerosis. eLife, doi: https://elifesciences.org/reviewed-preprints/95062v1 (2024)

S Hawkins, A Mondaini, SC Namboori, A Javed, A Bhinge. Exonuclease assisted mapping of protein-RNA interactions (ePRINT). bioRxiv, doi: https://doi.org/10.1101/2023.05.16.540978 (2023) 

Sophie Hawkins, Seema C. Namboori, Ammarah Tariq, Catherine Blaker, Christine Flaxman, Nidhi S. Dey, Peter Henley, Andrew Randall, Alessandro Rosa, Lawrence W. Stanton, Akshay Bhinge. Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis. Stem Cell Reports June 23, DOI:https://doi.org/10.1016/j.stemcr.2022.05.019 (2022)

Seema C. Namboori, Patricia Thomas, Ryan Ames, Sophie Hawkins, Lawrence O. Garrett, Craig R.G. Willis, Alessandro Rosa, Lawrence W. Stanton, Akshay Bhinge. Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons. Stem Cell Reports November 11, DOI:https://doi.org/10.1016/j.stemcr.2021.10.010 (2021)

Wang J, Jenjaroenpun P, Bhinge A, Angarica VE, Del Sol A, Nookaew I, Kuznetsov VA, Stanton LW. Single-cell gene expression analysis reveals regulators of distinct cell subpopulations among developing human neurons. Genome Research Nov;27(11):1783-1794.(2017)

*Bhinge, A., Namboori, S. C., Zhang, X., VanDongen, A. M. J., Stanton, L. W., Genetic Correction of SOD1 Mutant iPSCs Reveals ERK and JNK Activated AP1 as a Driver of Neurodegeneration in Amyotrophic Lateral Sclerosis. Stem Cell Reports 8, 856-869 (2017). (*co-corresponding author)

Bhinge, A., Namboori, S. C., Bithell, A., Soldati, C., Buckley, N. J., Stanton, L. W., MiR-375 is Essential for Human Spinal Motor Neuron Development and May Be Involved in Motor Neuron Degeneration. Stem Cells 34, 124-134 (2016).

Bhinge, A., Poschmann, J., Namboori, S. C., Tian, X., Jia Hui Loh, S., Traczyk, A., Prabhakar, S., Stanton, L. W., MiR-135b is a direct PAX6 target and specifies human neuroectoderm by inhibiting TGF-beta/BMP signaling. The EMBO Journal 33, 1271-1283 (2014).

*Polioudakis, D., *Bhinge, A. A., Killion, P. J., Lee, B. K., Abell, N. S., Iyer, V. R., A Myc-microRNA network promotes exit from quiescence by suppressing the interferon response and cell-cycle arrest genes. Nucleic Acids Research 41, 2239-2254 (2013). (*co-first author)

Lee, B. K., Bhinge, A. A., Battenhouse, A., McDaniell, R. M., Liu, Z., Song, L., Ni, Y., Birney, E., Lieb, J. D., Furey, T. S. et al., Cell-type specific and combinatorial usage of diverse transcription factors revealed by genome-wide binding studies in multiple human cells. Genome Research 22, 9-24 (2012).

ENCODE Consortium Project, An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57-74 (2012).

Lee, B. K., Bhinge, A. A., Iyer, V. R., Wide-ranging functions of E2F4 in transcriptional activation and repression revealed by genome-wide analysis. Nucleic Acids Research 39, 3558-3573 (2011).

*Shivaswamy, S., *Bhinge, A., Zhao, Y., Jones, S., Hirst, M., Iyer, V. R., Dynamic remodeling of individual nucleosomes across a eukaryotic genome in response to transcriptional perturbation. PLoS Biology 6, e65 (2008). (*co-first author, Selected as a Faculty of 1000 (Biology) article.)

ENCODE Consortium Project, Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799-816 (2007).

Bhinge, A. A., Kim, J., Euskirchen, G. M., Snyder, M., Iyer, V. R., Mapping the chromosomal targets of STAT1 by Sequence Tag Analysis of Genomic Enrichment (STAGE). Genome Research 17, 910-916 (2007).

Kim, J., Bhinge, A. A., Morgan, X. C., Iyer, V. R., Mapping DNA-protein interactions in large genomes by sequence tag analysis of genomic enrichment. Nature Methods 2, 47-53 (2005).

Grants

BRACE Dementia Research grant, 2023-2026

MRC IAA grant, 2023-2024

NC3R, 2023-2024 (Co-PI)

MRC New Investigator Research grant, 2020-2024

Drug Target discovery grant, 2022

Motor Neuron Disease Association and Open Innovation Platform grant, 2022

BRACE Alzheimer's Research grant, 2021-2022 (Co-I)

LSI Catalyst Fund 2021-2022

Academy of Medical Science Springboard award, 2018-2022

UEMS PhD studentship 2018-2022

Royal Society research grant, 2018-2019

Bhinge Lab members

  • Seema Namboori      (Lab manager & Postgraduate Researcher)
  • Johanna Ganssauge (LSI Ph.D. student)
  • Hayley Power            (MSc. Natural Sciences)
  • Isabelle Gray             (MSc. Natural Sciences)
  • Pragati Thakur           (Research Technician)
  • Tania Atienzar            (BRC Ph.D. student)
  • Yiyun (Aileen) Zhang (CSC Ph.D. student)
  • Antonio Fusciardi       (BRACE Ph.D. student)
  • Jeong Yeol Lee          (Ph.D. student with Ben Housden)

Research networks

Links


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Publications

Journal articles

Hawkins S, Namboori SC, Tariq A, Blaker C, Flaxman C, Dey NS, Henley P, Randall A, Rosa A, Stanton LW, et al (2022). Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis. Stem Cell Reports, 17(7), 1650-1665. Abstract.  Author URL.
Steg LC, Shireby GL, Imm J, Davies JP, Franklin A, Flynn R, Namboori SC, Bhinge A, Jeffries AR, Burrage J, et al (2021). Novel epigenetic clock for fetal brain development predicts prenatal age for cellular stem cell models and derived neurons. Mol Brain, 14(1). Abstract.  Author URL.
Namboori SC, Thomas P, Ames R, Hawkins S, Garrett LO, Willis CRG, Rosa A, Stanton LW, Bhinge A (2021). Single cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS motor neurons. bioRxiv 593129; doi: https://doi.org/10.1101/593129
Namboori SC, Thomas P, Ames R, Hawkins S, Garrett LO, Willis CRG, Rosa A, Stanton LW, Bhinge A (2021). Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons. Stem Cell Reports, 16(12), 3020-3035. Abstract.  Author URL.
Steg LC, Shireby GL, Imm J, Davies JP, Franklin A, Flynn R, Namboori SC, Bhinge A, Jeffries AR, Burrage J, et al (2020). Novel epigenetic clock for fetal brain development predicts prenatal age for cellular stem cell models and derived neurons. Abstract.
Lim S, Bhinge A, Bragado Alonso S, Aksoy I, Aprea J, Cheok CF, Calegari F, Stanton LW, Kaldis P (2017). Cyclin-Dependent Kinase-Dependent Phosphorylation of Sox2 at Serine 39 Regulates Neurogenesis. Mol Cell Biol, 37(16). Abstract.  Author URL.
Bhinge A, Namboori SC, Zhang X, VanDongen AMJ, Stanton LW (2017). Genetic Correction of SOD1 Mutant iPSCs Reveals ERK and JNK Activated AP1 as a Driver of Neurodegeneration in Amyotrophic Lateral Sclerosis. Stem Cell Reports, 8(4), 856-869. Abstract.  Author URL.
Wang J, Jenjaroenpun P, Bhinge A, Angarica VE, Sol AD, Nookaew I, Kuznetsov VA, Stanton LW (2017). Single-cell gene expression analysis reveals regulators of distinct cell subpopulations among developing human neurons. Genome Research, 27(11), 1783-1794. Abstract.
Bhinge A, Namboori SC, Bithell A, Soldati C, Buckley NJ, Stanton LW (2016). MiR-375 is Essential for Human Spinal Motor Neuron Development and May be Involved in Motor Neuron Degeneration. Stem Cells, 34(1), 124-134. Abstract.  Author URL.
Er JC, Leong C, Teoh CL, Yuan Q, Merchant P, Dunn M, Sulzer D, Sames D, Bhinge A, Kim D, et al (2015). NeuO: a fluorescent chemical probe for live neuron labeling. Angew Chem Int Ed Engl, 54(8), 2442-2446. Abstract.  Author URL.
Bhinge A, Poschmann J, Namboori SC, Tian X, Jia Hui Loh S, Traczyk A, Prabhakar S, Stanton LW (2014). MiR-135b is a direct PAX6 target and specifies human neuroectoderm by inhibiting TGF-β/BMP signaling. EMBO J, 33(11), 1271-1283. Abstract.  Author URL.
Polioudakis D, Bhinge AA, Killion PJ, Lee B-K, Abell NS, Iyer VR (2013). A Myc–microRNA network promotes exit from quiescence by suppressing the interferon response and cell-cycle arrest genes. Nucleic Acids Research, 41(4), 2239-2254.
Johnson R, Richter N, Bogu GK, Bhinge A, Teng SW, Choo SH, Andrieux LO, de Benedictis C, Jauch R, Stanton LW, et al (2012). A genome-wide screen for genetic variants that modify the recruitment of REST to its target genes. PLoS Genet, 8(4). Abstract.  Author URL.
(2012). An integrated encyclopedia of DNA elements in the human genome. Nature, 489(7414), 57-74.
(2011). A User's Guide to the Encyclopedia of DNA Elements (ENCODE). PLoS Biology, 9(4), e1001046-e1001046.
Lee B-K, Bhinge AA, Battenhouse A, McDaniell RM, Liu Z, Song L, Ni Y, Birney E, Lieb JD, Furey TS, et al (2011). Cell-type specific and combinatorial usage of diverse transcription factors revealed by genome-wide binding studies in multiple human cells. Genome Research, 22(1), 9-24. Abstract.
Lee B-K, Bhinge AA, Iyer VR (2011). Wide-ranging functions of E2F4 in transcriptional activation and repression revealed by genome-wide analysis. Nucleic Acids Research, 39(9), 3558-3573.
Smith AE, Chronis C, Christodoulakis M, Orr SJ, Lea NC, Twine NA, Bhinge A, Mufti GJ, Thomas NSB (2009). Epigenetics of human T cells during the G0-->G1 transition. Genome Res, 19(8), 1325-1337. Abstract.  Author URL.
Shivaswamy S, Bhinge A, Zhao Y, Jones S, Hirst M, Iyer VR (2008). Dynamic remodeling of individual nucleosomes across a eukaryotic genome in response to transcriptional perturbation. PLoS Biol, 6(3). Abstract.  Author URL.
Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, Thurman RE, et al (2007). Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature, 447(7146), 799-816. Abstract.
Bhinge AA, Kim J, Euskirchen GM, Snyder M, Iyer VR (2007). Mapping the chromosomal targets of STAT1 by Sequence Tag Analysis of Genomic Enrichment (STAGE). Genome Research, 17(6), 910-916. Abstract.
Bhinge A, Chakrabarti P, Uthanumallian K, Bajaj K, Chakraborty K, Varadarajan R (2004). Accurate detection of protein:ligand binding sites using molecular dynamics simulations. Structure, 12(11), 1989-1999. Abstract.  Author URL.
Kim J, Bhinge AA, Morgan XC, Iyer VR (2004). Mapping DNA-protein interactions in large genomes by sequence tag analysis of genomic enrichment. Nature Methods, 2(1), 47-53.
Dasgupta S, Chandran V, Bhinge A, Sewlikar S, Nimbkar A, Datta D (2004). Role of L-lysine HCl in adoptive immune therapy towards development of suitable tuberculosis vaccination. Indian J Exp Biol, 42(8), 758-765. Abstract.  Author URL.
Dasgupta S, Bhinge A, Chandran V, Sewlikar S, Nimbkar A, Datta D (2003). Role of L-lysine HCl in immunopotentiation towards development of suitable tuberculosis vaccination. Vaccine, 21(32), 4722-4727. Abstract.  Author URL.
Chakravarty S, Bhinge A, Varadarajan R (2002). A procedure for detection and quantitation of cavity volumes proteins. Application to measure the strength of the hydrophobic driving force in protein folding. J Biol Chem, 277(35), 31345-31353. Abstract.  Author URL.
Datta D, Bhinge A, Chandran V (2001). Lysine: is it worth more?. Cytotechnology, 36(1-3), 3-32. Abstract.  Author URL.
Datta D, Kundu PK, Biswas S, Dasgupta S, Bhinge A, Chandran V (2000). Effect of cationic amino acid, L-lysine and its polymers on the growth and secretion of hybridoma cell line OKT-3. Hybridoma, 19(4), 339-346. Abstract.  Author URL.

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External Engagement and Impact

Selected Invitations

  • Invited speaker, Splicing 2023, Portugal, 2023
  • Invited speaker, Univeristy of Bath, UK, 2023
  • Invited speaker, 19th Workshop on ALS, University of Lisbon, Portugal, 2022
  • Invited speaker, Automated cellular imaging meeting & workshop, Molecular Devices LLC, 2021
  • Invited speaker, University of Oxford, UK, 2019
  • Invited speaker, Universite’ de Nantes, France, 2019
  • Organiser, Stem Cell Singapore Symposium, Singapore, 2016
  • ISSCR, San Francisco, USA, 2016
  • Invited Speaker, Stem cells for modeling development and disease Symposium, Singapore, 2014
  • Invited Speaker, Development and Regeneration of Spinal Cord conference, Sitges, Spain, 2014
  • Invited Speaker, APOCB conference, Singapore, 2014
  • Non-coding RNAs in Development and Cancer conference, Keystone Symposia, Vancouver, Canada, 2013
  • Invited speaker, Centre for Cellular and Molecular Biology, Hyderabad, India, 2010
  • Invited speaker, Rockefeller University, New York, USA, 2009
  • Invited speaker, Yale University, Connecticut, USA, 2009
  • Invited speaker, the ENCODE (Encyclopedia of DNA Elements) consortium, Santa Cruz, USA, 2005

Awards and Honours

  • Academy of Medical Science Springboard award, UK, 2018
  • Career Development Award, A*STAR JCO Singapore, 2013
  • Lilly Singapore Centre for Drug Discovery Scholarship, Keystone Symposium, USA, 2009
  • Patricia L. Johnston Endowed Fellowship, University of Texas at Austin, USA, 2008
  • David Bruton, Jr. Graduate School Fellowship, University of Texas at Austin, USA, 2007
  • A.P. Bradie Endowed Fellowship, University of Texas at Austin, USA, 2006

Reviewer/Editor

  • Associate Editor, Frontiers in Molecular Neuroscience
  • Nucleic Acids Research
  • Human Molecular Genetics
  • Stem Cells
  • Nature Communications
  • Frontiers in Genetics
  • Frontiers in Cell and Developmental Biology
  • Bioinformatics
  • Stem Cell Reports
  • eLife
  • Frontiers in neuroscience

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Teaching

Frontiers in Neuroscience

Medical Cell Biology

Cell biology of disease

Modules

2023/24


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Supervision / Group

Postdoctoral researchers

  • Seema Namboori

Postgraduate researchers

  • Tania Atienzar (BRC PhD student)
  • Antonio Fusciardi (BRACE PhD student)
  • Johanna Ganssauge (LSI PhD student)
  • Isabelle Gray (MSc Natural Sciences)
  • Jeong Yeol Lee (PhD student)
  • Hayley Power (MSc Natural Sciences)
  • Yiyun (Aileen) Zhang (CSC PhD student)

Research Technicians

  • Pragati Thakur

Alumni

  • Jess Board
  • Lawrence Garrett
  • Rhiannon Haigh
  • Peter Henley
  • Elise Hobson
  • Charlie Marriott
  • James Moran
  • Jacob Quintin
  • Alice Robinson
  • Catherine White

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