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Swarup Lab research published in Nature Genetics

Contributed by Vivek Swarup, PhD

The brain is made up of billions of cells that are tightly coordinated in complex neural circuitry and are ultimately responsible for manifesting our memories, emotions, and personalities: the very essence of being human. Alzheimer’s Disease (AD) is one of the most prevalent neurodegenerative disorders worldwide and results in cognitive decline and memory loss, and we presently do not have effective treatments for AD. There is a pressing need to deepen our understanding of AD, and by studying how individual cells are changing in disease, or identifying those that are resilient to such changes, we can identify new targets for therapeutic development.

In our recent study published in Nature Genetics, we used cutting-edge sequencing technology to study how individual cells in AD patients differ from cognitively healthy individuals. Our work is also the first to study changes in DNA structure at the cellular resolution in any brain disorder. We identified key molecular pathways and potential regulators of neurodegeneration in specific cells. Additionally, we provide a gene regulatory map of AD genetic risk factors, such as APOE and BIN1, which will serve as a resource for others studying AD genetic risk.

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Vivek Swarup, PhD, Assistant Professor of Neurobiology & Behavior

About Vivek Swarup, PhD

My long-term research interests lie in comprehensive understanding of the role of transcriptional and regulatory pathways in human neurodegenerative diseases encompassing Alzheimer’s disease (AD). I use a systems biology and integrative genomics approach to gain deep insights into disease biology. At UCI, I am working closely in an integrated environment to understand the genetics and transcriptomics of neurodegenerative disorders and identify novel effective therapeutic targets for patients. During my postdoctoral training, I have gained experience in multi-omics analysis and used genomic approaches to unravel novel biology and targets in neurodegenerative dementia. I have also used systems biology approaches to unravel splicing regulators in Autism. I also have significant experience in using standard molecular biology and cellular neuroscience techniques as reflected by my PhD and master’s work. For my PhD degree, I moved to Canada and was awarded pre-doctoral FQRNT fellowship (awarded by FQRNT, Ministry of Education, Quebec, Canada to exceptional international PhD students) to pursue my research on amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD) in Prof. Jean-Pierre Julien’s lab, Quebec, Canada. I developed a new TDP-43 transgenic mouse model of ALS and discovered that TDP- 43 acts as a co-activator of p65 subunit of NF-kB and that deregulation of TDP-43 in ALS causes hyperactivated p65 response, which was published in the Journal of Experimental Medicine. I have also discovered novel biomarker for ALS, for which a US Patent was granted.