Dr. Harsha Kantamneni,Associate Professor
Information about Dr. Harsha Kantamneni at the University of Bradford.
- School of Pharmacy & Medical Sciences
(Faculty of Life Sciences) - Email:
- s.kantamneni@bradford.ac.uk
- Telephone:
- +44 1274 236072
Biography
Research
Research projects
| Role | Date | Title/description | Funder | Award |
|---|---|---|---|---|
| PI | 2018-04-01T00:00:00 | Sporadic motor neuron disease (MND) accounts for around 90% of cases with the remaining 10% being inherited. However, the mechanisms causing disease are often indistinguishable, suggesting that functional analysis of genes linked with inherited MND can identify mechanisms underlying sporadic cases. Studies in multiple patient cohorts have shown that inactivating mutations in the TBK1 (TANK binding kinase 1) gene cause both inherited and sporadic MND & frontotemporal dementia. TBK1 interacts with and phosphorylates optineurin and p62, promotes mitophagy and is part of a common pathway known to regulate autophagy and neurodegeneration. SOCS3 (suppressor of cytokine signalling 3) is an inducible protein that binds and regulates the ubiquitination and degradation of specific substrates, including TBK1. As SOCS3 down-regulates TBK1 expression, we hypothesise that disruption of the SOCS3-TBK1 interface in neurons can rescue TBK1 function by decreasing its degradation and thus represents a tractable new target for therapeutic intervention to limit neurodegeneration in MND. | ||
| Co-PI | 2019-07-01T00:00:00 | Co-PI | ||
| Co-PI | 2018-11-30T00:00:00 | |||
| PI | 2016-02-04T00:00:00 | GABAB receptors are heterodimers of GABAB1 and GABAB2 subunits and require both subunits for functional signalling. Previously I 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, I hypothesize that the loss of NMDA receptor-mediated inhibition represents a novel mechanism by which excitotoxicity triggers the death of damaged neurons. May 2017; Alzheimer’s Research Trust Network (PI): The SOCS3/TBK1 interface: An opportunity for development of novel therapeutics to prevent MND and neurodegeneration March 2016; Alzheimer’s Research UK - Yorkshire regional network (PI): ESCRT proteins as therapeutic targets in Alzheimers disease March 2016; Royal Society (PI): Mechanisms regulating NMDA-mediated down-regulation of neuronal GABAB receptors in ischemia | ||
| Co-PI | 2016-02-01T00:00:00 | ARUK | ||
| PI | 2017-12-10T00:00:00 | |||
| PI | 2017-05-01T00:00:00 | Protein degradation is of fundamental importance for neuronal function and perturbation of degradative pathways has been implicated in multiple neurodegenerative disorders but particularly Alzheimers 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. 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. 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. |
Professional activities
Information about education, employment and areas of particular interest for Dr. Harsha Kantamneni is as follows:
Employment
- King Faisal Specialist Hospital, Riyadh, Saudi Arabia - Research Fellow in the year 2011 (specified as 01/01/2011)
- University of Bristol - Research Associate in the year 2005 (specified as 01/01/2005)
Education
- DR. MGR Medical University, India - Bachelors
- Sheffield Hallam University - MSc
- University of Bristol - PhD
- City of Bristol College - APD
- University of Bradford - postgraduate certificate
Publications
There are 14 publications involving or that are attributed to Dr. Harsha Kantamneni. They are listed as:
- book chapter (1)
- editorial (1)
- peer reviewed journal (12)
Book Chapter
| Title | Year | Publication name | Journal | Volume | Pages | Authors | Editors | ISSN | Publisher | DOI | Location |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Modulation of Neurotransmission by the GABAB Receptor | 2016 | Kantamneni, Sriharsha |
Editorial
| Title | Year | Publication name | Journal | Volume | Pages | Authors | Editors | ISSN | Publisher | DOI | Location |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Editorial: Cerebrovascular and Neurodegenerative Diseases - New Insights Into Molecular Cell Biology and Therapeutic Targets | 2019 | Frontiers in Neurology | 10 | Saha S.;Kantamneni S. | 1664-2295 | 10.3389/fneur.2019.01322 |
Peer Reviewed Journal
| Title | Year | Publication name | Journal | Volume | Pages | Authors | Editors | ISSN | Publisher | DOI | Location |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Agonist-induced PKC phosphorylation regulates GluK2 SUMOylation and kainate receptor endocytosis | 2011 | Konopacki, F.A.; Jaafari, N.; Rocca, D.L.; Wilkinson, K.A.; Chamberlain, S.E.; Rubin, P.; Kantamneni, Sriharsha; Mellor, J.R.; Henley, J.M. | |||||||||
| SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity | 2012 | Chamberlain, S.E.; Gonzàlez-Gonzàlez, I.M.; Wilkinson, K.A.; Konopacki, F.A.; Kantamneni, Sriharsha; Henley, J.M.; Mellor, J.R. | |||||||||
| Differential regulation of GABAB receptor trafficking by different modes of N-methyl-D-aspartate (NMDA) receptor signaling | 2014 | Kantamneni, Sriharsha; Gonzàlez-Gonzàlez, I.M.; Luo, J.; Cimarosti, H.; Jacobs, S.C.; Jaafari, N.; Henley, J.M. | |||||||||
| Cross-talk and regulation between glutamate and GABAB receptors | 2015 | Kantamneni, Sriharsha | |||||||||
| SUMOylation Is Required for Glycine-Induced Increases in AMPA Receptor Surface Expression (ChemLTP) in Hippocampal Neurons | 2013 | Jaafari, N.; Konopacki, F.A.; Owen, T.F.; Kantamneni, Sriharsha; Rubin, P.; Craig, T.J.; Wilkinson, K.A.; Henley, J.M. | |||||||||
| Modulation of neurotransmission by the GABA |
2016 | Receptors | 29 | 109 - 128 | Kantamneni S. | 1048-6909 | 10.1007/978-3-319-46044-4_7 | ||||
| GISP increases neurotransmitter receptor stability by down-regulating ESCRT-mediated lysosomal degradation. | 2009 | Neuroscience Letters | 452 | Kantamneni S;Holman D;Wilkinson KA;Nishimune A;Henley JM; | 0304-3940 | 10.1016/j.neulet.2009.01.011 | |||||
| Ischaemia differentially regulates GABA(B) receptor subunits in organotypic hippocampal slice cultures. | 2009 | Neuropharmacology | 56 | Cimarosti H;Kantamneni S;Henley JM; | 1873-7064 | 10.1016/j.neuropharm.2009.03.007 | |||||
| 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. | 2011 | The Journal of neuroscience : the official journal of the Society for Neuroscience | 31 | Ceolin L;Kantamneni S;Barker GR;Hanna L;Murray L;Warburton EC;Robinson ES;Monn JA;Fitzjohn SM;Collingridge GL;Bortolotto ZA;Lodge D; | 1529-2401 | 10.1523/JNEUROSCI.0418-11.2011 | |||||
| Activity-dependent SUMOylation of the brain-specific scaffolding protein GISP. | 2011 | Biochemical and Biophysical Research Communications | 409 | Kantamneni S;Wilkinson KA;Jaafari N;Ashikaga E;Rocca D;Rubin P;Jacobs SC;Nishimune A;Henley JM; | 1090-2104 | 10.1016/j.bbrc.2011.05.060 | |||||
| GISP binding to TSG101 increases GABA receptor stability by down-regulating ESCRT-mediated lysosomal degradation. | 2008 | Journal of Neurochemistry | 107 | Kantamneni S;Holman D;Wilkinson KA;Corrêa SA;Feligioni M;Ogden S;Fraser W;Nishimune A;Henley JM; | 1471-4159 | 10.1111/j.1471-4159.2008.05580.x | |||||
| GISP: a novel brain-specific protein that promotes surface expression and function of GABA(B) receptors. | 2007 | Journal of Neurochemistry | 100 | Kantamneni S;Corrêa SA;Hodgkinson GK;Meyer G;Vinh NN;Henley JM;Nishimune A; | 0022-3042 | 10.1111/j.1471-4159.2006.04271.x |