Home > Academics > Academic Units > Schools > Bio Science > Nihar Ranjan Jana
Professor
Bio Science
Neurodegenerative disorders, such as Alzheimer’s disease (AD), Huntington’s disease (HD) and Parkinson’s disease (PD), affect millions of people worldwide. Regardless of numerous attempts to find a treatment approach, therapeutics for these devastating diseases is yet to be discovered. One of the common pathological hallmarks of most age-related neurodegenerative disorders is the accumulation of mutant disease proteins as inclusion bodies. Appearance of aggregates of the misfolded mutant disease proteins suggest that cells are unable to efficiently degrade them, and failure of clearance leads to the severe disturbances of the cellular protein quality control system. Furthermore, the cellular ability to maintain protein homeostasis declines with age. Therefore the mechanism that restores protein homeostasis either by up-regulating the function of chaperones or enhancing the clearance of mutant disease proteins could be promising therapeutic approach.
In my laboratory, we are using HD and AD as a model system to understand the mechanistic basis of impaired protein homeostasis and how that can be restored. We have reported that Ube3a function as a cellular protein quality control ubiquitin ligase and involved in the clearance of misfolded disease proteins (J. Biol. Chem., 2008, 2009 and Neurobiol. Aging,2013). Deficiency of Ube3a in HD mice brain also increased global aggregate load and aggravated HD pathogenesis (Hum. Mol. Genet., 2014). In collaboration with Scientist at IACS, Kolkata, we are also using nanoparticle-based strategy to prevent fibrillation and aggregation of amyloid proteins (ACS Appl. Mat. Inter, 2016, 2017).
My laboratory also uses biochemical, cell biological and genetic approaches to understand the physiological function of Ube3a and how its gain as well as loss of function is linked with autism and autism spectrum disorders. We are also screening pharmacological inducers of Ube3a, which might be useful in the therapy of learning and memory disorders.
Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease by Tanaka M., Machida Y. , Niu S. , Ikeda T. , Jana N. R., Doi H. , Kuroshawa M. , Nekooki M. , Nukina N. Nature Medicine 10 148-151 (2004)
Altered proteasomal function due to the expression of polyglutamine-expanded truncated N-terminal huntingtin induces apoptosis by caspase activation through mitochondrial cytochrome c release by Jana N. R., Zemskov E. A., Wang G. , Nukina N. Human Molecular Genetics 10 1049-1059 (2001)
Dexamethasone induces heat shock response and slows down disease progression in mouse and fly models of Huntington s disease. by Maheshwari M., Bhutani S. , Das A. , Mukherjee R. , Sharma A. , Kino Y. , Nukina N. , Jana N. R. Human Molecular Genetics 23 2737-2751 (2014)
Deficiency of Ube3a in Huntington's disease mice brain increases aggregate load and accelerates disease pathology by Maheshwari M., Shekhar S. , Singh B. K., Jamal I. , Vatsa N. , Kumar V. , Sharma A. , Jana N. R. Human Molecular Genetics 23 6235-6245 (2014)
Ube3a deficiency inhibits amyloid plaque formation in APPswe/PS1 E9 mouse model of Alzheimer s disease by Singh B. K., Vatsa N. , Kumar V. , Sekhar S. , Sharma A. , Jana N. R. Human Molecular Genetics 26 4042-4054 (2017)
Topoisomerase inhibitor topotecan delays the disease progression in a mouse model of Huntington s disease by Shekhar S., Vatsa N. , Kumar V. , Singh B. K., Jamal I. , Sharma A. , Jana N. R. Human Molecular Genetics 26 420-429 (2017)
Azadiradione restores protein quality control and ameliorates the disease pathogenesis in a mouse model of Huntington s disease by Singh B. K., Vatsa N. , Nelson V. K., Kumar V. , Kumar S. S., Mandal S. C., Pal M. , Jana N. R. Molecular Neurobiology 55 6337-6346 (2018)
Dietary restriction improves proteostasis and increases life span through endoplasmic reticulum hormesis by Matai L., Sarkat G. C., Chamoli M. , Malik Y. , Kumar S. S., Rautela U. , Jana N. R., Chakraborty K. , Mukhopadhyay A. PNAS 116 17383-17392 (2019)
Simvastatin restores HDAC1/2 activity and improves behavioural deficits in Angelman syndrome model mouse by Kumar V., Joshi T. , Vatsa N. , Singh B. K., Jana N. R. Frontiers in Molecular Neuroscience 12 1-11 (2019)
Down-Regulation of miRNA-708 Promotes Aberrant Calcium Signaling by Targeting Neuronatin in a Mouse Model of Angelman Syndrome by Vatsa N., Kumar V. , Singh B. K., Kumar S. S., Sharma A. , Jana N. R. Frontiers in Molecular Neuroscience 12 1-12 (2019)
Regulation of Activity-dependent Synaptic Function and Plasticity by Azadiradione Science and Engineering Research Board (SERB)
Regulation of Experience-dependent Synaptic Plasticity by Ube3a: Implication in Autism Spectrum Disorders DBT, NEW DELHI
Understanding the Mechanism of Clearing Neurotoxic Protein Aggregates Via Autophagy Modulation by Designed Manochaperone Science and Engineering Research Board (SERB)
Development of a New Screening Platform for the Discovery of Novel Therapeutics to Cure Neurodegenerative Diseases Department of Science and Technology, Ministry of Science and Technology (International Multilateral and Regional Cooperation Division)
Restoration of Protein Quality Control as a Therapeutic Strategy to Combat Age-associated Neurodegenerative Disorders ISIRD, SRIC
Processing of Complex Sound Signals including Vocalizations in Mice Models of Autism and Different types of Sensorineural Hearing Loss Department of Science and Technology (International Cooperation Division)
Sudipta Jana
Area of Research: Synaptic function and plasticity
Trisha Kundu
Area of Research: Neurodegenerative disease
Amiyangshu De
Area of Research: Neurobiology
Ann Soniya M Micheal
Area of Research: Auditory Neural Processing
Bhaskarjyoti Giri
Area of Research: Neuroscience