Research

We work in different fields of Neurobiology

Integrative functional genomic approaches to understand neurodegenerative diseases


We are using multi-omic approaches to understand molecular mechanism of neurodegenerative diseases like Alzheimer’s disease and Fronto-temporal dementia (FTD). Researchers need a better understanding of the role of distinct cell-types in disease pathophysiology to improve the design of therapeutic interventions for AD and FTD. Current transcriptomic approaches can powerfully investigate quantitative molecular phenotypes and pathways underlying disease progression in a genome-wide manner. Yet, they lack the specificity needed to comprehend the role of cell-type specific changes in disease pathophysiology. Our work will identify the molecular mechanisms underlying neurodegeneration and investigate how they differ from normal aging. Using single-cell multi-omic approaches coupled with bulk tissue sequencing, we hope to directly answer some of these questions.



MODEL-AD : Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease


MODEL-AD is a NIH/NIA consortia tasked with the development of next generation of in vivo AD models based on human data, institute a standardized and rigorous process for characterization of animal models, align the pathophysiological features of AD models with corresponding stages of clinical disease using translatable biomarkers and ensure rapid availability of animal models, protocols and validation data to all researchers for preclinical drug development. As part of Functional genomics and bioinformatics core of MODEL-AD at UCI, our lab is tasked to generate and analyze high throughput multi-omic datasets generated using newer models of AD, and make the data readily available for open science. MODEL-AD data can be found here.

Unraveling mechanisms involved in neuronal injury and regeneration using systems biology approaches


We are using systems biology approaches to understand the transcriptomic and proteomic changes happening during nerve injury both in the peripheral and central nervous system. While the regeneration capacity of injured neuron in the central nervous system (CNS) is limited, peripheral nervous system (PNS) maintain some capacity to regenerate. Using genomic approaches, we are trying to understand the temporal changes happening in PNS and CNS neurons after injury. Working with Adelson Program in Neural Repair and Rehabilitation (APNRR) researchers, we are also interested in unravel core regulators of neuronal regeneration and find novel drug targets to promote regeneration.



Publications

Selected Publications are shown, for a full list use this link.




Othero-Garcia M, Mahajani SU, Wakhloo D, Tang W, Xue Y-Q, Morabito S, Pan J, Oberhauser J, Madira AE, Shakouri T, Deng Y, Allison T, Zihuai He, Lowry WE, Kawaguchi R, Swarup V, Cobos I. Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer’s disease. Neuron. 2022 Jul 21:S0896-6273(22)00600-6. doi: 10.1016/j.neuron.2022.06.021. Epub ahead of print.





Shi Z, Das S, Morabito S, Miyoshi E, Swarup V. Protocol for single-nucleus ATAC sequencing and bioinformatic analysis in frozen human brain tissue. STAR Protocols. 2022 Jun 17;3(3):101491. doi: 10.1016/j.xpro.2022.101491.





Trubetskoy V, Pardiñas AF, Qi T, Panagiotaropoulou G, …, Roth J, Rothermundt M, Rutten BPF, Saker-Delye S, Salomaa V, Sanjuan J, Santoro ML, … PsychENCODE; … Schizophrenia Working Group of the Psychiatric Genomics Consortium. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature. 2022 Apr;604(7906):502-508. doi: 10.1038/s41586-022-04434-5. Epub 2022 Apr 8.





Kiani Shabestari S, Morabito S, Danhash EP, McQuade A, Sanchez JR, Miyoshi E, Chadarevian JP, Claes C, Coburn MA, Hasselmann J, Hidalgo J, Tran KN, Martini AC, Chang Rothermich W, Pascual J, Head E, Hume DA, Pridans C, Davtyan H, Swarup V, Blurton-Jones M. Absence of microglia promotes diverse pathologies and early lethality in Alzheimer's disease mice. Cell Reports. 2022 Jun 14;39(11):110961. doi: 10.1016/j.celrep.2022.110961.





Miyoshi E, Morabito S, Swarup V.Systems biology approaches to unravel the molecular and genetic architecture of Alzheimer’s disease and related tauopathies. Neurobiology of Disease. 2021 Dec;160:105530. doi: 10.1016/j.nbd.2021.105530. Epub 2021 Oct 9.





Morabito S, Miyoshi E, Michael N, Shahin S, Martini AC, Head E, Silva J, Leavy K, Perez-Rosendahl M, Swarup V. Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer's disease. Nature Genetics. 2021 Aug;53(8):1143-1155. doi: 10.1038/s41588-021-00894-z. Epub 2021 Jul 8.





Li Y, He X, Kawaguchi R, Zhang Y, Wang Q, Monavarfeshani A, Yang Z, Chen B, Shi Z, Meng H, Zhou S, Zhu J, Jacobi A, Swarup V, Popovich PG, Geschwind DH, He Z. Microglia-organized scar-free spinal cord repair in neonatal mice. Nature. 2020 Nov;587(7835):613-618. doi: 10.1038/s41586-020-2795-6. Epub 2020 Oct 7.





Morabito S, Miyoshi E, Michael N, Swarup V. Integrative genomics approach identifies conserved transcriptomic networks in Alzheimer's disease. Human Molecular Genetics. 2020 Oct 10;29(17):2899-2919. doi: 10.1093/hmg/ddaa182.





Alim I, Caulfield JT, Chen Y, Swarup V, Geschwind DH, Ivanova E, Seravalli J, Ai Y, Sansing LH, Ste Marie EJ, Hondal RJ, Mukherjee S, Cave JW, Sagdullaev BT, Karuppagounder SS, Ratan RR. Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke. Cell. 2019 May 16;177(5):1262-1279.e25. doi: 10.1016/j.cell.2019.03.032. Epub 2019 May 2.



PsychENCODE Consortium. Revealing the brain's molecular architecture. Science. 2018 Dec 14;362(6420):1262-1263. doi: 10.1126/science.362.6420.1262.



Swarup V, Hinz FI, Rexach JE, Noguchi KI, Toyoshiba H, Oda A, Hirai K, Sarkar A, Seyfried NT, Cheng C, Haggarty SJ; International Frontotemporal Dementia Genomics Consortium, Grossman M, Van Deerlin VM, Trojanowski JQ, Lah JJ, Levey AI, Kondou S, Geschwind DH. Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia. Nat Med. 2019 Jan;25(1):152-164. doi: 10.1038/s41591-018-0223-3. Epub 2018 Dec 3.



Chandran V, Gao K, Swarup V, Versano R, Dong H, Jordan MC, Geschwind DH. Inducible and reversible phenotypes in a novel mouse model of Friedreich's Ataxia. Elife. 2017 Dec 19;6. pii: e30054. doi: 10.7554/eLife.30054.



Parras A, Anta H, Santos-Galindo M, Swarup V, Elorza A, Nieto-González JL, Picó S, Hernández IH, Díaz-Hernández JI, Belloc E, Rodolosse A, Parikshak NN, Peñagarikano O, Fernández-Chacón R, Irimia M, Navarro P, Geschwind DH, Méndez R, Lucas JJ. Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing. Nature. 2018 Aug;560(7719):441-446. doi: 10.1038/s41586-018-0423-5. Epub 2018 Aug 15



Seyfried NT, Dammer EB, Swarup V, Nandakumar D, Duong DM, Yin L, Deng Q, Nguyen T, Hales CM, Wingo T, Glass J, Gearing M, Thambisetty M, Troncoso JC, Geschwind DH, Lah JJ, Levey AI. A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease. Cell Syst. 2017 Jan 25;4(1):60-72.e4. doi: 10.1016/j.cels.2016.11.006. Epub 2016 Dec 15.



Parikshak NN, Swarup V, Belgard TG, Irimia M, Ramaswami G, Gandal MJ, Hartl C, Leppa V, Ubieta LT, Huang J, Lowe JK, Blencowe BJ, Horvath S, Geschwind DH. Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism. Nature. 2016 Dec 15;540(7633):423-427. doi: 10.1038/nature20612. Epub 2016 Dec 5. Erratum in: Nature. 2018 Aug;560(7718):E30.



Swarup V, Geschwind DH. Alzheimer's disease: From big data to mechanism. Nature. 2013 Aug 1;500(7460):34-5. doi: 10.1038/nature12457. Epub 2013 Jul 24.



Swarup V, Audet JN, Phaneuf D, Kriz J, Julien JP. Abnormal regenerative responses and impaired axonal outgrowth after nerve crush in TDP-43 transgenic mouse models of amyotrophic lateral sclerosis. J Neurosci. 2012 Dec 12;32(50):18186-95. doi: 10.1523/JNEUROSCI.2267-12.2012.



Swarup V, Phaneuf D, Dupré N, Petri S, Strong M, Kriz J, Julien JP. Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor κB-mediated pathogenic pathways. J Exp Med. 2011 Nov 21;208(12):2429-47. doi: 10.1084/jem.20111313. Epub 2011 Nov 14.



Swarup V, Phaneuf D, Bareil C, Robertson J, Rouleau GA, Kriz J, Julien JP. Pathological hallmarks of amyotrophic lateral sclerosis/frontotemporal lobar degeneration in transgenic mice produced with TDP-43 genomic fragments. Brain. 2011 Sep;134(Pt 9):2610-26. doi: 10.1093/brain/awr159. Epub 2011 Jul 13.

Enabling research through Big data





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.

Swarup Lab

Lab Members

Take a closer look into our amazing team.

    Sudeshna Das

    Postdoctoral Scholar

    Sudeshna completed her PhD dissertation work from DRDO, MoD, India. She has also worked as ICMR-SRF and Assistant Prof. (contract) in two different gov. universities of India. Her current research work at UCI focuses on understanding genetics and transcriptomics of neurodegenerative disorders for identification of novel effective therapeutic targets.

    Nora Emerson

    Graduate Student Researcher

    Nora received her B.A. in Behavioral Neuroscience at University of San Diego. She is interested in studying spatial transcriptomics and other multi-omics approaches to understand more about the mechanisms behind neurodegeneration. When not in the lab, she enjoys yoga, reading and learning to golf.

    Nellie Kwang

    MD-PhD Student

    Nellie is a UC Irvine alum and received her B.S. in Developmental & Cell Biology and Cognitive Sciences. She is interested in understanding the role of APOE in neurodegenerative diseases using multi-omics approaches. Outside of the lab, Nellie loves trying new foods with her husband, singing karaoke, making art, and cuddling with her four cats and 130-lb Great Dane.


    Veronica Sung Woo

    Graduate Student

    I received my B.A. in English at UCLA and my M.S. in Molecular Microbiology and Immunology at USC. I am examining the usage of human neural organoids and how they can be combined with mouse models to recapitulate Alzheimer's disease pathology. In my spare time, I enjoy outdoor activities including water sports, hiking ,and camping.

    Johnny Boutros

    Graduate Student

    Johnny received his B.A. in Environmental Science and Policy along with a minor in Biological Sciences from UCI in 2022. He is currently interested in using transcriptomics to understand the processes that contribute to Blood-Brain Barrier degradation in neurodegenerative diseases. In his free time, Johnny enjoys brewing coffee, hiking, and cooking.

    Negin Rahimzadeh

    Graduate Student

    Negin received her B.S. in Molecular, Cell, and Developmental Biology from the University of California, Los Angeles. She is keenly interested in understanding the structural, functional, and molecular alterations that holistically contribute to neurological disorders through integrative multi-omics analysis. Outside the lab, Negin enjoys exploring philosophy, savoring coffee, going on hikes, and playing racket sports.

    Ze Tristan Shi

    CMB Graduate Student

    Ze received his degree in Biotechnology at the Johns Hopkins University. He believes that big data empowers scientists in learning the mechanism of disease progression and wants to use integrative functional genomic approaches to study neurodegenerative disease. Outside the lab, he enjoys extreme sports that bring excitement. Despite his extreme fear of altitude, he went skydiving.

    Luis Solano

    Mathematical, Computational, and Systems Biology (MCSB) PhD student

    Luis received his B.S. from UC San Diego and his M.S. from CSU Fullerton. He is excited by multi-omic experimental design and their big-data integrative analyses. In his spare time, you’ll find him enjoying a cup of coffee or finding some new music to listen to.

    Joey Wong

    GR2, MSTP Student

    I am a third year MD/PhD student at UC Irvine. My research interests lies in using multi-omic approaches to characterize molecular changes associated with neuropathologies prevalent in aging and Alzheimer's disease and related dementias, and their consequences on cognitive function. In my free time, I enjoy hiking, paddleboarding, yoga, and gardening!


    Shushrruth Sai

    MCSB Graduate Student

    Sai received his B.S. in Biotechnology and Computer Science from India. His work focuses on developing machine-learning methods on multi-omics data to understand how non-coding variants can result in diseases at the single-cell level. Outside of the lab, Sai enjoys exploring new places and trying different cuisines.

      Arshi Shahin

      Lab Manager

      Arshi received her Masters in business administration (MBA) from India. She manages all day-to-day financials and ordering of the lab. She is interested in learning NGS library preparation using liquid handling platforms. When not in the lab, she enjoys cooking, yoga and playing with her kids.

      Utkarsh Tiwari

      Assistant Specialist

      Utkarsh is a data science graduate from UCI with a passion for applying machine learning and deep learning models to uncover valuable insights from complex biological data. My expertise lies in harnessing the power of AI to solve challenging problems in the life sciences. Beyond the data-driven world, I'm a fitness enthusiast who enjoys pushing my limits at the gym, striving for balance between intellectual growth and physical well-being.

      Raj Sanghavi

      MCS Graduate Student

      Raj received his Masters degree in Computer Science from the University of California Irvine in 2024. He is interested in leveraging technologies for creating applications for a greater social good. Beyond academics and professional endeavors, Raj enjoys exploring trekking trails, embarking on hiking adventures, and leveraging technology for community-driven initiatives.

      Madhu Sudhana Saddala

      Associate Specialist, UCI MIND

      Dr. Madhu Sudhana Saddala is an accomplished Bioinformatics Scientist currently serving as an Associate Specialist at UCI MIND, University of California, Irvine. With over a decade of research experience, Dr. Saddala specializes in bioinformatics, genomics, and proteomics. His work is primarily focused on deciphering the molecular mechanisms of neurodegenerative diseases such as Alzheimer's disease and Frontotemporal dementia using single-cell multi-omic approaches.

      Zak Jefferis

      Undergraduate Researcher

      My name is Zak and I am in my 4th year at UCI with a major in neurobiology. I joined the Swarup lab in September 2023 and I work alongside Janice to assist Veronica with her research. In my personal time, I enjoy working out, listening to music, and spending time with friends and family.

      Janice Lan

      Undergraduate Researcher

      I am an undergraduate student at the University of California, Irvine, majoring in Neurobiology with a minor in Management. I am particularly fascinated by the applications of IPSC in regenerative medicine, especially in the bioengineering of organoids to model Alzheimer’s disease. Outside of academics, I love dancing hip hop, exploring new food spots, and traveling to Taiwan every summer!

      Trina Nguyen

      Undergraduate Researcher

      My name is Trina Nguyen, and I’m a Biological Sciences major at UCI. I’m interested in whole genome sequencing and single-nucleus sequencing to understand the genetic and molecular mechanisms behind neurodegenerative diseases like AD. Outside of the lab, I enjoy paddle-boarding, pottery, and binging new shows!

      Andres Alonso Castaneda

      Associate Data Analyst

      Whenever not in the lab, Andres enjoys hiking, bouldering, horseback riding, fromsoftware games, films, and running. Andres is also an active member of EMS and volunteers with the homeless population.

      Teaching




      • NB206 Molecular Neuroscience (Fall Quarter)


        NB206 is a core course of Interdepartmental Neuroscience Graduate Program (INP) at UCI. The course is aimed to understand molecular and cellular mechanisms involved in neuronal function, including control of gene expression, post-transcriptional and post-translational processing, RNA and protein targeting, cell death mechanisms, neurogenetics, and molecular genetic basis of neurological disorders. NB206 is team taught and Dr. Swarup co-teaches with Drs. Blurton-Jones and Cramer. Dr.Swarup teaches the gene regulation and neurogenetics portion of the course highlighting cutting edge genomic approaches that are available to investigate and understand gene-regulation in an unbiased genome-wide manner. Sample syllabus can be found here (subject to change)



      • Bioinformatics and Systems Biology (Winter Quarter)


        This course is an advanced course geared towards gaining practical hands-on experience in analyzing RNA-seq, ATAC-seq, proteomics and single-cell RNA-seq data. Dr. Swarup will teach the basics of data processing and QC, differential gene/protein expression, co-expression network analysis, and correlation analysis. Since students taking this course are not required to have any programming skills, Dr. Swarup will also teach basics in Linux/Bash command line and statistical programming language R. Classes (NB227) are held in winter quarter every Tues, Friday (10:30AM-12noon). Sample syllabus can be found here (subject to change).



      • Bio 37: Brain Dysfunction and Repair (Spring Quarter)


        Bio 37 is team taught and Dr. Swarup teaches with Drs. Green and Busciglio. This course aimed at non-Biological science Majors with an interest in understanding how the brain works and how it controls our bodies and gives rise to our thoughts, emotions and memories, and how it goes awry in disease. Bio 37 requires no prior biology knowledge and will cover how the cells that make up our brains function together. Dr Swarup will teach how the brain is impacted in a number of brain disorders, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Down Syndrome, Depression, Anxiety, Frontotemporal Dementias, and damage due to injury to specific brain regions. Sample syllabus can be found here (subject to change)

      Datasets

      Datasets Analyzed by the Lab

      Single-nuclei epigenomic and transcriptomic landscape in Alzheimer's disease


      The gene regulatory landscape of the brain is highly dynamic in health and disease, coordinating a menagerie of biological processes across distinct cell-types and cell states. Fully contextualizing molecular signatures of disease with respect to specific cell-types requires a holistic multi-layered experimental and analytical approach. While single-cell transcriptomics has been used extensively in human disease systems, very few single-cell epigenomic studies have been carried out in primary disease samples. Here, we present a multi-omic single-cell study of 191,897 nuclei in late-stage Alzheimer’s Disease (AD), in which we profiled chromatin accessibility and gene expression in the same biological samples, uncovering vast glial heterogeneity in late-stage AD. We describe cis-regulatory relationships in specific cell-types at AD risk loci defined by genome wide association studies (GWAS), demonstrating the utility of this multi-omic single-cell framework for uncovering disease and cell-type-specific regulatory mechanisms. Trajectory analysis of glial populations displayed dynamic transcription factor regulatory patterns in the transition between healthy and diseased states. Further, we introduce scWGCNA, a co-expression network analysis strategy robust to the sparsity of single-cell data, to perform a systems-level meta-analysis of AD transcriptomics. Finally, this work is highly accessible through our intuitive web-portal, allowing for straightforward interrogation of this multi-omic dataset. A shiny app has been generated to easily visualize the data. Visit AD Single-nuclei Multi-Omics Shiny App here





      Human Alzheimer's Brain Gene-Expression Datasets


      Analysis of Human Alzheimer's disease brain gene-expression datasets generated by AMP-AD consortium as well as other published datasets. All the datasets were processed as described in Morabito et al., 2019 and the consensus network analysis was also performed. A shiny app has been generated to easily visualize the data. Visit AD Gene-Expression Shiny App here





      Control Brain Single-Nuclei Expression Dataset


      Analysis of Human brain single-nuclei gene-expression dataset generated from 4 control brain samples. The dataset was processed and analyzed as described in Morabito et al., 2019. A shiny app has been generated to easily visualize the data. Visit Control Single-Nuclei Gene-Expression Shiny App here



      It's just not about data

      Address:

      3224 Biological Sciences III
      Irvine, CA 92697.

      Phone:

      (949) 824-3182

      Count of curious minds visiting our website:

      Error loading visitor count