Dr. Paramita Chakrabarty

Understanding the pathogenetic mechanisms in Alzheimers’ disease and Related dementias

Dr. Paramita ChakrabartyAssistant Professor, Neuroscience and CTRND;
Wilder Family Fellow
MBI Fellow in Research Leadership

Training
Post Doc, Neuroscience (Todd Golde) University of Florida, 2009-2011
Post Doc, Neuroscience (Todd Golde), Mayo Clinic College of Medicine, 2005-2009
PhD., Biochemistry, Jawaharlal Nehru University, India, 2003

 

 

 

Contact Dr. Chakrabarty
Office: 352-273-7271
Lab: 352-294-8764
email: pchakrabarty@ufl.edu

Research Interests

Understanding the role of innate immunity in Alzheimer’s and Parkinson’s disease.Cytokines and chemokines have been intimately associated with neurodegenerative pathology in Alzheimer’s disease (AD) and AD related disorders. However, the question remains whether neuroinflammation is the driving force behind the neurodegenerative pathology specifically leading to a self-reinforcing feedback loop to promote the disturbed protein homeostasis in these diseases. Some key areas of research in my laboratory are:

1) examining the role of immune milieu in proteinaceous aggregate clearance in mouse models of AD and ADRD;

2) mapping the relative progression of protein homeostasis failure, immune activation and neurodegeneration;

3) elucidating the functional role of immune molecules that are genetic risk factors for AD;

4) harnessing endogenous immune molecules as potential disease modifying therapies;

This work is funded by National Institute of Aging, National Institute of Neurological Disorders and Stroke and Florida Department of Health.

Understanding the role of Apolipoprotein E in Alzheimer’s pathogenesis.Apolipoprotein E is the strongest genetic risk factor in Alzheimer’s disease and yet, aside from its role in amyloid βmetabolism, its role in tauopathy remains relatively unknown. Our laboratory is interested in understanding how different Apolipoprotein E isoforms modify disease progression in mouse models of tauopathy.

This work is funded by National Institute of Aging.

Exploring how proteinopathy spreads in rodent models of neurodegenerative diseases.To understand the spread of proteinopathy in AD and ADRD, my laboratory is interested in examining how tau and α-synuclein seeds trigger induction and transmission of proteinaceous aggregates in the brain. These ongoing experiments will be instrumental in understanding the physiological basis of disease progression in AD and related disorders.

This work is funded by Alzheimer’s Association.

Understanding how innate immunity affects ALS/Lou Gehrig’s disease.Inflammatory signaling precedes and can contribute to neuropathological changes in ALS. Our laboratory is interested in uncovering the role of different immune mediators in disease pathogenesis in mouse models of familial ALS.

This work was funded by ALS Association.

Understanding selective neuronal vulnerability in neurodegenerative disorders. Selective populations of neurons are exquisitely vulnerable in neurodegenerative disorders – for example, the nigrostriatal pathway is affected in Parkinsonism and its dysfunction underlies the clinical symptom. We identified a specific cytokine – Interferon γ– as a trigger for selective nigrostriatal degeneration in wild type mice. To further understand and refine the concept of selective neuronal vulnerability, we are conducting experiments to examine whether this is a result of non cell autonomous signaling and further to characterize the factors that underlie this phenotype.

 

Current Publications

  1. Sorrentino, Z.A., Xia, Y., Funk, C., Riffe, C.J., Rutherford, N., Ceballos-Diaz, C., Sacino, A., Price, N., Golde, T.E., Giasson, B.I., Chakrabarty, P. Motor Neuron Loss Precedes Neuroinflammation in a Model of α-Synuclein-induced Neurodegeneration. Accepted (September 2018). Neurobiol Dis. 2018 Sep 5. pii:S0969-9961(18)30552-1. doi: 10.1016/j.nbd. 2018.09.005.
  2. Chakrabarty, P., Li A., Ladd, T., et al. Soluble TLR5 as an amyloid β therapeutic agent. J Exp Med.2018 Aug 29. pii: jem.20180484. doi: 10.1084/jem.20180484.
  3. Strickland, M.R., Koller, E.J., Deng, D.Z., Ceballos-Diaz, C., Golde, T.E., Chakrabarty, P. Ifngr1 and Stat1 mediated Ifn-γ canonical signaling drives nigrostriatal degeneration. Neurobiol Dis.2017 Nov 28;110:133-14.
  4. Sorrentino Z.A., Brooks M.M.T., Hudson III V., Golde T.E., Giasson B.I., Chakrabarty P. Intrastriatal injection of α-synuclein can lead to widespread synucleinopathy independent of neuroanatomic connectivity. Mol Neurodegener. 2017 May 29; 12:40.
  5. Koller E.J, Brooks M.M.T., Golde T.E., Giasson B.I., Chakrabarty P. Inflammatory pre-conditioning limits the seeded induction of α-synuclein pathology in wild type mice. Mol Neurodegener. 2017 Jan 3;12(1):1

Link To PubMed