COLLEGE OF MEDICINE AND HEALTH
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Dr Akshay Bhinge

Dr Akshay Bhinge

LSI Research Fellow

 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

 

Research keywords

  • Induced Pluripotent Stem Cells (iPSC)
  • Motor Neuron Disease (Amyotrophic lateral Sclerosis)
  • Disease modelling in a dish
  • Neurodegeneration
  • Neuronal maturation and ageing
  • 3D models of brain and spinal cord
  • CRISPR-Cas9 genome editing
  • ChIP-sequencing
  • Single cell RNA-sequencing
  • Epigenomics
  • Non-coding RNAs
  • Regulatory networks
  • Bioinformatics

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.

Key Publications

1.   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 2017 Nov;27(11):1783-1794.

2.   *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)

3.   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).

4.   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).

5.   *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)

6.   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).

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

8.   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).

9.   *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.)

10.   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).

11.   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).

12.   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).

13.   Bhinge, A., Chakrabarti, P., Uthanumallian, K., Bajaj, K., Chakraborty, K., Varadarajan, R., Accurate detection of protein:ligand binding sites using molecular dynamics simulations. Structure 12, 1989-1999 (2004).

 

Grants

MRC New Investigator Research Grant, 2020-2023

Wellcome Trust ISSF Pre-seedcorn award, 2019

Academy of Medical Science Springboard award, 2018-2021

Royal Society research grant, 2018-2019

Wellcome Trust ISSF Seedcorn award, 2018

Wellcome Trust ISSF Seedcorn award, 2017

 

Bhinge Lab

  • Sophie Hawkins (Ph.D. student)
  • James Moran  (Ph.D. student)
  • Jeong Yeol Lee (Joint Ph.D. student with Ben Housden)
  • Peter Henley (Professional Training Year student)
  • Jacob Quentin (Professional Training Year student)
  • Seema Namboori (Research Technician)

Research networks

Links


Publications

Key publications | Publications by category | Publications by year

Publications by category


Journal articles

Namboori SC, Thomas P, Ames R, Garrett LO, Willis CRG, Stanton LW, Bhinge A (2019). Single cell transcriptomics identifies master regulators of dysfunctional pathways in SOD1 ALS motor neurons. https://www.biorxiv.org/content/10.1101/593129v1.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.
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, GuigĂł 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.
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.

Conferences

Chronis C, Smith AE, Christodoulakis M, Bhinge A, Orr SJ, Lea NC, Twine N, Mufti GJ, Iyer V, Thomas NSB, et al (2009). Epigenetic code of primary human T cells during the first cell cycle.  Author URL.
Smith AE, Chronis C, Christodoulakis M, Bhinge A, Twine N, Lea N, Mufti G, Lyer V, Thomas S (2008). Epigenetic analyses of T cells during the G0 to G1 transition.  Author URL.

Publications by year


2019

Namboori SC, Thomas P, Ames R, Garrett LO, Willis CRG, Stanton LW, Bhinge A (2019). Single cell transcriptomics identifies master regulators of dysfunctional pathways in SOD1 ALS motor neurons. https://www.biorxiv.org/content/10.1101/593129v1.abstract

2017

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.

2016

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.

2015

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.

2014

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.

2013

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.

2012

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

(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.
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.

2009

Chronis C, Smith AE, Christodoulakis M, Bhinge A, Orr SJ, Lea NC, Twine N, Mufti GJ, Iyer V, Thomas NSB, et al (2009). Epigenetic code of primary human T cells during the first cell cycle.  Author URL.
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.

2008

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.
Smith AE, Chronis C, Christodoulakis M, Bhinge A, Twine N, Lea N, Mufti G, Lyer V, Thomas S (2008). Epigenetic analyses of T cells during the G0 to G1 transition.  Author URL.

2007

Birney E, Stamatoyannopoulos JA, Dutta A, GuigĂł 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.

2004

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.

2003

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.

2002

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.

2001

Datta D, Bhinge A, Chandran V (2001). Lysine: is it worth more?. Cytotechnology, 36(1-3), 3-32. Abstract.  Author URL.

2000

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.

Akshay_Bhinge Details from cache as at 2020-12-05 07:22:47

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External Engagement and Impact

Selected Invitations/Conference organised

  • Invited speaker at the University of Oxford, UK, 2019
  • Invited speaker at the Universite’ de Nantes, France, 2019
  • Organiser for the Stem Cell Singapore Symposium, Singapore, 2016
  • Invited Speaker at the Stem Cell Singapore Symposium, Singapore, 2016
  • ISSCR, San Francisco, USA, 2016
  • Invited Speaker at the Stem cells for modeling development and disease Symposium, Singapore, 2014
  • Invited Speaker at the Development and Regeneration of Spinal Cord conference, Sitges, Spain, 2014
  • Invited Speaker at the APOCB conference, Singapore, 2014
  • Non-coding RNAs in Development and Cancer conference, Keystone Symposia, Vancouver, Canada, 2013
  • Invited speaker at the Centre for Cellular and Molecular Biology, Hyderabad, India, 2010
  • Invited speaker at Rockefeller University, New York, USA, 2009
  • Invited speaker at Yale University, Connecticut, USA, 2009
  • Invited speaker at 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

Other

Ad-hoc Reviewer

  • 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

Teaching

CSC4008 Frontiers in Neuroscience

BIO3086 Cell biology of disease

Supervision / Group

Postgraduate researchers

  • Sophie Hawkins
  • Jeong Yeol Lee
  • James Moran

Research Technicians

  • Seema Chandramohan Namboori

Alumni

  • Johanna Ganssauge
  • Lawrence Garrett

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