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Dr Sriharsha Kantamneni

PositionLecturer in Therapeutics
LocationNorcroft building, 2.12
DepartmentSchool of Pharmacy
Telephone+44 (0) 1274 236072
LinkedInVisit my LinkedIn profile

Research Interests (key words only)

Neuronal membrane proteins, receptor trafficking and degradation, protein-protein interactions, Glutamate / GABA receptors and post-translational modification

Teaching and Supervisory Responsibilities


Unit lead:

  • Foundation Studies 1, Unit 2 and 3 – Cell structure and components
  • Foundation Studies 1, Unit 6 – Receptors and function
  • Nutrition, Metabolism and Reproduction 3, Units 3 and 4 – Gastrointestinal problems

Unit team member:

  • Senses Thoughts and Movement 1, Units 5 and 6 – Musculoskeletal problems
  • Senses Thoughts and Movement 2, Units 5 – Musculoskeletal problems

Student Selected Component:

  • t-strand (Research topics)

Capability in Pharmacy years 1, 2, 3 and 4

Personal Academic Tutor for 18 students

Biomedical Science and Clinical Sciences

  • Human Physiology (1st year)
  • Central Nervous System Mechanisms, Disorders and Therapeutics (3rd year)


Administrative Responsibilities

MPharm Admission Tutor and outreach activities co-ordinator

Study History

  • Pharmacy, Bachelors, DR. MGR Medical University, India - 1998
  • MSc Pharmacology and Biotechnology, Sheffield Hallam University, UK - 2000
  • PhD Molecular and Cellular Neuroscience, University of Bristol, UK - 2004
  • APD in Management Studies (level7), City of Bristol College, UK - 2006
  • PGCHEP (postgraduate certificate in higher education practice) (Sep 2013 – July 2015)
    University of Bradford, Bradford, UK

Professional History

2011- June 2013: Research Fellow, Dept of Genetics, Research centre, King Faisal Specialist Hospital, Riyadh, Saudi Arabia

2005 - 2010: Research Associate, MRC Centre for Synaptic Plasticity, University of Bristol, Bristol, UK

Professional Activities

  • Member of International Society for Neurochemistry
  • Member of British Neuroscience Association
  • Member of British Pharmacological Society
  • Member of Biochemical Society
  • Member of British Society for Cell Biology

Research Areas

ESCRT proteins as therapeutic targets in Alzheimer's disease

Protein degradation is of fundamental importance for neuronal function and perturbation of degradative pathways has been implicated in multiple neurodegenerative disorders but particularly Alzheimer's disease (AD). ESCRT proteins mediate trafficking of membrane proteins to lysosomes and their degradation. ESCRT consists of four multiprotein complexes (ESCRT–0, –I, –II and –III) that mediate endocytosis of cell surface proteins including glutamate receptors (Kantamneni et al., 2009) through multivesicular bodies (MVBs) to lysosomes for degradation. Previously, ESCRT-III subunit CHMP2B immunopositivity has been identified in granulovacuolar degeneration bodies in neurons of AD hippocampus (Yamazaki et al 2010). One of the key feature of early onset AD models is the intracellular amyloid-β (Aβ) accumulation that precedes the appearance of Aβ in extracellular plaques. Recently it has been shown that Aβ is generated through proteolytic processing of amyloid precursor protein (APP), which is localised to MVBs and that it is delivered to lysosomes for degradation (Edgar et al., 2015). Transient depletion of either ESCRT-0 or -I components, inhibited targeting of APP to MVBs and the subsequent delivery to lysosomes. This resulted in increased intracellular Aβ accumulation, accompanied by dramatically decreased Aβ secretion. In summary, ESCRT machinery has multiple roles in limiting intracellular Aβ accumulation through targeting of APP to the lysosomes for degradation as well as trafficking & degradation of neurotransmitters receptors. Based on these observations, my lab is testing the hypothesis that, since in AD models ESCRTs function is abnormal, studying ESCRT mechanisms and its regulation in neurons has the potential to identify new molecular targets for therapeutic intervention in AD.

Mechanisms regulating NMDA-mediated down-regulation of neuronal GABAB receptors in ischemia

GABAB receptors are heterodimers of GABAB1 and GABAB2 subunits and require both subunits for functional signalling. Previously we have shown that exposing neurons to extreme metabolic stress using oxygen/glucose deprivation (OGD) ischemic model, increases GABAB1 but decreases GABAB2 surface expression in neurons. The increase in surface GABAB1 involves enhanced recycling and is blocked by the NMDA receptor-selective antagonist AP5. The decrease in surface GABAB2 is also blocked by AP5 and by inhibiting degradation pathways. These results indicate that NMDAR activity is a critical regulator of GABABR trafficking and function to regulate neuronal responsiveness and survival. Building on this work, we hypothesize that the loss of NMDA receptor-mediated inhibition represent a novel mechanism by which excititoxicity triggers death of damaged neurons.

Current Projects

  • March 2016; Alzheimer’s Research Trust Network (PI): ESCRT proteins as therapeutic targets in Alzheimer's disease
  • March 2016; Royal Society (PI): Mechanisms regulating NMDA-mediated down-regulation of neuronal GABAB receptors in ischemia
  • Feb 2016; ARUK (Co-PI): Real-time imaging of molecular mechanisms underlying synaptic dysfunction and neurodegeneration in Alzheimer’s disease


  • Chapter: Modulation of Neurotransmission by the GABAB Receptor (2016) Sriharsha Kantamneni Book Name: GABAB Receptor, pp 109-128 Volume 29 of the series The Receptors DOI 10.1007/978-3-319-46044-4_7
  • Sriharsha Kantamneni (2015) Cross-talk and regulation between glutamate and GABAB receptors. Front Cell Neurosci. 9:135. doi: 10.3389/fncel.2015.00135
  • Sriharsha Kantamneni*, Immaculada M. Gonzàlez-Gonzàlez, Helena I Cimarosti, Jia Luo, Nadia Jaafari and Jeremy M Henley* (2014). Differential regulation of GABAB receptor trafficking by different modes of NMDA receptor signaling. J Biol Chem. 289(10): 6681–6694. (*co-corresponding author)
  • Nadia Jaafari, Filip Konopacki, Thomas F. Owen, Sriharsha Kantamneni, Philip Rubin, Tim J. Craig, Kevin A. Wilkinson and Jeremy M. Henley (2013). USUMOylation is required for glycine-induced increases in AMPA receptor surface expression (ChemLTP) in hippocampal neuronsU. PLoS ONE. 8(1):e52345
  • Sophie E L Chamberlain, Inmaculada M González-González, Kevin A Wilkinson, Filip A Konopacki, Sriharsha Kantamneni, Jeremy M Henley & Jack R Mellor (2012). SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity Nature Neuroscience. 15(6):845-52
  • Sriharsha Kantamneni, Kevin A. Wilkinson, Nadia Jaafari, Emi Ashikaga, Daniel Rocca, Philip P. Rubin, Susan C. Jacobs, Atsushi Nishimune and Jeremy M. Henley. (2011) Activity-dependent SUMOylation of the brain-specific scaffolding protein GISP. Biochem Biophys Res Commun. 409(4):657-62
  • Filip Konopacki, Nadia Jaafari, Dan L. Rocca, Kevin A. Wilkinson, Sophie Chamberlain, Philip Rubin, Sriharsha Kantamneni, Jack R. Mellor and Jeremy M. Henley (2011). Agonist-induced PKC phosphorylation regulates GluK2 SUMOylation and kainate receptor endocytosis. Proc Natl Acad Sci USA. 108(49):19772-7
  • Laura Ceolin, Sriharsha Kantamneni, Gareth R. Barker, Lydia Hanna, Lynnette Murray, Elizabeth C. Warburton, Emma S. Robinson, James A. Monn, Stephen M. Fitzjohn, Graham L. Collingridge, Zuner A. Bortolotto and David Lodge. (2011) Study of Novel Selective mGlu2 Agonist in the Temporo-Ammonic Input to CA1 Neurons Reveals Reduced mGlu2 Receptor Expression in a Wistar Substrain with an Anxiety-Like Phenotype. J Neuroscience. 31(18):6721-31
  • Sriharsha Kantamneni, Kevin A. Wilkinson and Jeremy M. Henley. (2011) Ubiquitin regulation of neuronal excitability. Nature Neuroscience. 14(2):126-8
  • Sriharsha Kantamneni, David Holman*, Kevin A. Wilkinson*, Atsushi Nishimune and Jeremy M. Henley. (2009) UGISP increases neurotransmitter receptor stability by down-regulating ESCRT-mediated lysosomal degradation. Neuroscience Letters. 452(2): 106-10
  • Helena Cimarosti*, Sriharsha Kantamneni* and Jeremy M. Henley. (2009) Changes in GABAB receptors following ischemic challenges in organotypic cultures. Neuropharmacology. 56(8): 1088-96. (*Equal contribution)
  • Sriharsha Kantamneni*, David Holman*, Kevin A. Wilkinson, Sônia A.L. Corrêa, Marco Feligioni, Simon Ogden, William Fraser, Atsushi Nishimune and Jeremy M. Henley. (2008) GISP binding to TSG101 increases GABAB2 receptor stability by down-regulating ESCRT-mediated lysosomal degradation. J. Neurochemistry. 107(1): 86-95. (*Equal contribution)
  • Sriharsha Kantamneni, Sônia A.L. Corrêa, Gina K. Hodgkinson, Guido Meyer, Ngoc Nga Vinh, Jeremy M. Henley and Atsushi Nishimune. (2007). UGISP: A novel brain specific protein that promotes surface expression and function of GABAB receptors. J. Neurochemistry 100(4); 1003-17

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