Nilkantha Sen, PhDAssociate Professor
Nilkantha Sen, PhD, joined the University of Pittsburgh Department of Neurologoical Surgery in March of 2017 as an associate professor.
After graduating from Indian Institute of Chemical Biology—one of the most prestigious institutes of India—Dr. Sen joined Johns Hopkins University in 2010 as a post-doctoral fellow under the mentorship of Solomon H Snyder, MD. His work studied the mechanism involved for nitric oxide-induced neuronal cell death and he discovered a novel mechanism which was shown to play a key role in cell death associated with several neurodegenerative diseases such as Alzheimer’s Disease, Parkinson’s Disease and brain injury.
Dr. Sen also identified a novel neuroprotective protein, GOSPEL, which can protect cell death in the brain during neurodegeneration. Furthermore, his findings further clarified the molecular mechanism associated with both hyperactivity and neurotoxicity following exposure of cocaine, providing a new insight in the field of drug abuse.
While working in the field of nitric oxide, Dr. Sen also explored another newly discovered gasotransmitter, hydrogen sulfide (H2S) in the brain and in peripheral tissues such as the liver. However, its role in physiology and pathology was poorly understood. Dr. Sen found that, like nitric oxide, H2S also modifies proteins through a process of sulfhydration and shows that sulfhydration of several proteins affects their biological functions and influences the outcome of neurodegenerative diseases.
In 2012, Dr. Sen joined Georgia Regents University as an assistant professor and started working in the field of traumatic brain injury. His major interest in TBI is to understand the role of gasotransmitter in the pathology. Recently, he has identified a novel mechanism that can explain the edema and cell death following TBI.
Dr. Sen has published 38 papers in refereed journals including seven review articles. Total citations have exceeded 2500.
Specialized Areas of Interest
Elucidating molecular mechanisms associated with pathology of TBI; cognitive dysfunction, memory impairment and vision impairment following TBI; pre-clinical testing of potential compounds against TBI in mice model.
Professional Organization Membership
Indian Science Congress Association, India
Society of Biological Chemistry, India
Society for Neuroscience, USA
Education & Training
BSc, Chemistry, Calcutta University, India 1998
MSc, Biochemistry, Calcutta University, India, 2000
PhD, Oxidative Stress, Cell Death, Indian Institute of Chemical Biology, 2006
Post-Doc Fellowship, Neuroscience, Johns Hopkins Medical College, USA, 2010
Honors & Awards
- Emerging Scientist Award, Augusta University, Ga., 2016
- Young Outstanding Basic Science Faculty Award, Georgia Regents University, 2016
- Oral Podium Award, 2nd International Conference on H2S Biology and Medicine, 2012
- Young Scientist Award (W. Barry Wood, Jr), Johns Hopkins University, 2010
- Third Prize, Annual Poster Competition, Johns Hopkins University, 2009
- Best Poster Award, International Symposium on Molecular Mechanism of Diseases, 2005
Sen T, Sen N. Isoflurane-induced inactivation of CREB through histone deacetylase 4 is responsible for cognitive impairment in developing brain. Neurobiology of Disease 96:12-21, 2016.
Sen T, Sen N. Treatment with an activator of hypoxia-inducible factor 1, DMOG provides neuroprotection after traumatic brain injury. Neuropharmacology 107:79-88, 2016.
Mir S, Sen T, Sen N. Cytokine-induced GAPDH sulfhydration effects PSD95 degradation and memory. Molecular Cell 56(6):786-95, 2014.
Kapoor S, Farook JM, Saha R, Sen N. Foxo3a Transcriptionally up-regulates AQP4 and induces cerebral edema following Traumatic Brain Injury. Journal of Neuroscience 33(44):17398-403, 2013.
Farook JM, Shields J, Tawfik A, Markand S, Sen T, Smith SB, Brann D, Dhandapani KM, Sen N. GADD34 induces cell death through inactivation of Akt following traumatic brain injury. Cell Death and Disease 4:e754, 2013.
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in humans, affecting more than 1.7 million Americans each year. The economic burden of taking care of TBI-patients exceeded more than $78 billion in 2014. People surviving TBI suffer from cognitive and motor impairment, psychological disturbances, and visual impairment. Unfortunately, no therapeutic intervention has been established to treat TBI patients. Having this background in mind, we have set the following three goals for our lab:
- Develop intervention strategies to reduce TBI-related outcomes,
- Improve cognitive and motor functions after TBI, and
- Reduce/prevent TBI-associated neurological disorders.
To identify the therapeutic strategies against TBI, we need to understand the characteristic features of TBI. TBI is multifactorial in nature and is mostly characterized by cell death, edema, inflammation, impairment in neurogenesis and angiogenesis, and a decrease in axonal myelination. We have established a controlled cortical impact (CCI) model of TBI in the laboratory and have found that inactivation of a protein kinase, Akt, is responsible for neuronal cell death following TBI. Inactivation of Akt causes a decrease in the phosphorylation level of several proteins including Bad, GSK3β, and Foxo3a.
In another effort, we have shown that activation of Foxo3a, due its reduction in its phosphorylation, level leads to an augmentation in mRNA level of AQP4, which is critical for edema formation following TBI. Depletion of Foxo3a in mouse brains leads to an attenuation of edema following TBI.
On the other hand, several studies have shown that a couple of regenerative pathways, including activation of hypoxia-inducible transcription factor 1 (HIF-1α), reduces cellular damage following TBI. However, endogenous activation of these pathways is not enough to provide neuroprotection after TBI. We tested whether sustained activation of HIF-1α may provide neuroprotection following TBI. To our surprise, we found that treatment with an activator of HIF-1α, DMOG provides neuroprotection and augments neurogenesis and angiogenesis by preventing inactivation of Akt following TBI.
A compelling amount of evidence suggests that augmentation in the level of proinflammatory cytokines such as IL-1β is responsible for memory impairment in neurodegenerative diseases and in post-traumatic brain disorders (PTSD). However, the mechanism is poorly understood. Our lab has shown that IL-1β-induced augmentation, in the level of intracellular H2S and GAPDH sulfhydration, and stimulates degradation of PSD95, which holds the key to synaptic density and memory formation. Thus, preventing the loss of PSD95 may provide a therapeutic target against several disorders and brain injury where induction of IL- 1β manifests pathology of these diseases.