Tuesday, August 21, 2018
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Research

Rita Christopher,
MBBS, MD
Professor 
Thrust Areas of Research
Cerebrovascular disorders,
Neurometabolic disorders

Dr. Rita Christopher’s lab

Cerebrovascular diseases continue to be an important cause of death and disability in India. Consequently, our research is focused on evaluating molecular and genetic moieties within the pathophysiological pathways in atherothrombosis to identify potential biomarkers which would aid in risk prediction and contribute to the development of these disorders. Using a mass spectrometry-based proteomic approach, we have identified potential biomarkers for ischemic and hemorrhagic stroke. We have conducted extensive studies on the role of gene variants and other metabolic abnormalities  with the risk of cerebral venous thrombosis, an important cause of stroke in young women. We are currently evaluating the role of vitamin D status, genetic variants of the vitamin D metabolic pathway enzymes, and the genetic variants of the renin-angiotensin-aldosterone system in the etio-pathogenesis of cerebral small vessel disease and vascular cognitive impairment. We are also profiling extracellular and circulating microRNAs  in cerebral small vessel disease,  cerebral aneurysms and other neurological disorders  with an aim to identify and validate molecular biomarkers that can be used for rapid, accurate and point-of-care testing for these disorders.

A significant number of patients with progressive neurological disorders have not been diagnosed despite extensive workups. In order to facilitate the diagnosis, we conduct mass spectrometry-based targeted metabolomic  studies leading the diagnosis of several rare disorders. In 2007, we have established the first state-of the-art facility for screening for  inborn errors of intermediary metabolism – disorders of amino acid metabolism, fatty acid oxidation defects and organic acidemias. Since then, we have identified more than 1000 cases. We have also established a high-throughput, robust, and reliable mass spectrometry-based method to screen for lysosomal storage disorders using dried blood spots collected on filter paper. The diseases selected in the present panel include Gaucher disease, Pompe disease, Fabry disease, Niemann-Pick disease types A and B and Krabbe disease. This method can be  used to screen newborns and symptomatic cases for these disorders.  We have standardised a  low cost, mass –spectrometry-based method to screen for  X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disorder.  Validation of this method is presently being carried out.  Early diagnosis of these inherited neurometabolic disorders before the onset of irreversible pathologies will lead to better outcomes for current and proposed therapies.

Nandakumar DN
MBBS, MD, DNB
Additional Professor
Thrust Area of Research

Primary brain tumors

Dr.Nandakumar’s lab

Glioblastoma (GBM) is one of the most common and most malignant tumours of the central nervous system. It is notorious for its highly infiltrative and invasive behavior. Despite new diagnostic techniques and combined modality therapy prognosis remains dismal. Decades of surgical therapy, radiotherapy and chemotherapy have failed to drastically change survival. Glioma cells have exceptional ability to infiltrate normal brain, often along blood vessels or nerve fibres. This feature makes complete radical surgical resection virtually impossible and leading in almost all cases to tumor recurrence. Several factors are thought to contribute to the invasive and migratory properties of GBM cells, interacting with the microenvironment and enhancing motility and invasion. We aim at understanding glutamate excitotoxicity in GBM, glutamate receptor pathway, the role inflammatory and regulatory cytokines and its signaling on migration, proliferation and invasiveness of tumour and contribute to the understanding of the complex biological interactions that regulate glioblastoma growth, invasion and recurrence.

M.M. Srinivas Bharath,
MSc, Ph.D
Additional Professor

Thrust Areas of Research

Neuro-, myo-degenerative diseases, Neurotrauma

Dr. Srinivas Bharath’s lab

Neurodegenerative diseases, myodegenerative diseases and injury-related pathologies share several common mechanisms such as necrosis/apoptosis, inflammation, genetic/epigenetic alterations, oxidative stress and mitochondrial dysfunction. Among these, redox mechanisms and mitochondrial dynamics are important events. While these are primary factors in certain pathological conditions, they seem to be down-stream events in others. Our laboratory focuses on delineating the molecular details of redox and mitochondrial dynamics in CNS diseases (Parkinson’s disease, behavioural disorders), muscle diseases (muscular dystrophies and myopathies) and neurotrauma (traumatic brain injury), using experimental models (cell and mouse models) and human tissue samples. To fulfill this objective, we employ various biochemical, histopathological, behavioural and proteomic approaches.

Sarada Subramanian,
MSc, Ph.D
Professor & Head

Thrust Area of Research
Alzheimer’s disease

Dr. Sarada Subramanian’s lab

We focus on the development of therapeutic strategies to Alzheimer’s disease (AD). AD is one of the leading causes of dementia in the elderly, with more than 40 million individuals currently affected worldwide. AD is caused by the selective loss/ dysfunction of neurons particularly those expressing nicotinic acetylcholine receptors in specific brain regions including the neocortex and hippocampus. Spatial learning, working memory, and long-term memory impairments are some of the earliest symptoms expressed in AD. The pathological hallmarks of AD include intracellular neurofibrillary tangles (NFT) consisting of hyperphosphorylated form of the microtubule associated protein tau and senile plaques comprising of the aggregated peptide amyloid ß (Aß). An increase in acetylcholinesterase (AChE), a key enzyme in the cholinergic nervous system, around the senile plaques and NFT is a common feature of AD neuropathology. Aß (1-42) is generated from a lager precursor protein (APP) by the proteolytic action of specific cleavage enzymes called ß- and γ-secretases. Mutations in either the Aß precursor protein or the processing enzymes account for familial cases of AD (<5%). However, vast majority of AD cases (>95%) are sporadic, significantly influenced by the presence of an apolipoprotein allele E4, dietary lifestyle and more importantly, the metabolic disorders such as diabetes and obesity.

We address the multiple targets of AD as therapeutic strategies. The methodology involves bacterial expression of the culprit peptides of Aβ, Tau and their analogs, immunotherapeutic interventions using peptide- and DNA vaccines in combination with adjuvants approved for use in humans, multiple antigenic peptide systems and conformational antibodies, development of non-transgenic rodent model systems, assessment of their suitability for AD research by physiological and by biochemical means, evaluation of metabolic (dys)function and the reversal on cognitive functions, selection of nootropic herbal extracts containing anti-Alzheimer effects and the development of relevant in vitro and in vivo assay methods.