Dr Akshay Bhinge
LSI Research Fellow
+44 (0)1392 727459
Living Systems Institute T02.16
Living Systems Institute, University of Exeter, Stocker Road, Exeter, EX4 4QD
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 development of future therapies aimed at halting or even reversing the relentless neuronal loss.
• 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
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative condition characterized by a 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. I use patient-derived and genome edited pluripotent stem cells to develop human models of ALS in vitro and investigate these models using single-cell RNA-Seq and epigenomics. My aim is to uncover the mechanisms by which neuronal death occurs in order to develop therapies aimed at halting the neurodegeneration.
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).