Ali Mortazavi, PhD, MS

Research Interests

Transcriptional Regulation, Genomics, Long-range chromatin interactions, ChIP-seq, RNA-seq

Academic Distinctions

2004 CSULA Chemistry and Biochemistry Graduate Student Award
2008 Caltech Lawrence L. and Audrey W. Ferguson Prize for outstanding doctoral thesis in biology
2013 NIH New Innovator Award
2014 UC Irvine Distinguished Assistant Professor Award for Research

Appointments

2008 – 2011 Gordon and Betty Moore Cell Center Postdoctoral Fellowship, Caltech
2009 – 2011 Beckman Institute Postdoctoral Fellowship, Caltech

Research Abstract

Applications of genomics, computation, and sequencing technologies to the analysis of transcriptional regulation in development.

My laboratory explores how gene regulatory networks that underlie development are encoded in the human genome and we seek to understand their “grammar” and dynamics using both laboratory and computational methods. We focus on how tissue-specific transcriptional enhancers work, and whether their expression levels and target genes can be predicted from in vivo protein-DNA interactions (as measured using ChIP-seq), open chromatin (from DNase-seq) and RNA expression (from RNA-seq) of both normal and perturbed differentiation time courses. No reliable computational methods yet exist to link distal enhancers to their target genes (which can be many genes and up to a megabase-pair away in mammals) using sequence, expression or ChIP-data alone. While this identification problem is extremely difficult when considering large and complex genomes linearly, it would be a relatively easy problem if we could capture the three-dimensional interaction of the looping enhancers with their target promoters. We are, therefore, working with techniques that capture long-range chromatin interactions globally, such as ChIA-PET, in developmental time courses in order to integrate these long-range data with ChIP-seq, DNase-seq, and RNA-seq into testable gene regulatory networks. We are also interested in what fraction of these long-range interactions account for phenotypic variation between individuals and whether they are more likely to be conserved in vertebrates.

Publications

R Murad, A Macias-Muñoz, A Wong, X Ma, A Mortazavi (2021) Coordinated gene expression and chromatin regulation during Hydra head regeneration
Genome Biology and Evolution

Chen GT, Tifrea DF, Murad R, Habowski AN, Lyou Y, Duong MR, Hosohama L, Mortazavi A, Edwards RA, Waterman ML (2021) Disruption of beta-catenin dependent Wnt signaling in colon cancer cells remodels the microenvironment to promote tumor invasion
Mol Cancer Res

Chan D, Feng C, England WE, Wyman D, Flynn RA, Wang X, Shi Y, Mortazavi A, Spitale RC (2021) Diverse functional elements in RNA predicted transcriptome-wide by orthogonal RNA structure probing
Nucleic Acids Res

Forner S, Kawauchi S, Balderrama-Gutierrez G, Kramár EA, Matheos DP, Phan J, Javonillo DI, Tran KM, Hingco E, da Cunha C, Rezaie N, Alcantara JA, Baglietto-Vargas D, Jansen C, Neumann J, Wood MA, MacGregor GR, Mortazavi A, Tenner AJ, LaFerla FM, Green KN (2021) Systematic phenotyping and characterization of the 5xFAD mouse model of Alzheimer’s disease
Scientific Data

Rebboah E, Reese F, Williams K, Balderrama-Gutierrez G, McGill C, Rodriguez I, Liang H, Wold BJ, Mortazavi A (2021) Mapping and modeling the genomic basis of differential RNA isoform expression at single-cell resolution with LR-Split-seq
Genome Biology

Ionkina AA, Balderrama-Gutierrez G, Ibanez KJ, Phan SHD, Cortez AN, Mortazavi A, Prescher JA (2021) Transcriptome analysis of heterogeneity in mouse model of breast cancer
Breast Cancer Res.

Arreola MA, Soni N, Crapser JD, Hohsfield LA, Elmore MRP, Matheos DP, Wood MA, Swarup V, Mortazavi A, Green KN (2021) Microglial dyshomeostasis drives perineuronal net and synaptic loss in a CSF1R+/- mouse model of ALSP, which can be rescued via CSF1R inhibitors
Science Advances

Murad R, Avanes A, Ma X, Geng S, Mortazavi A, Momand J (2021) Transcriptome and chromatin landscape changes associated with trastuzumab resistance in HER2+ breast cancer cells
Gene

Macias-Munoz A, Mortazavi A (2021) A Bioinformatics pipeline for investigating molecular evolution and gene expression using RNA-seq
JOVE

Baglietto-Vargas D, Forner S, Cai L, Martini AC, Laura Trujillo-Estrada, Swarup V, Nguyen MMT, Huynh KD, Javonillo DI, Tran KM, Phan J, Jiang S, Kramár EA, Nuñez-Diaz C, Balderrama-Gutierrez G, Garcia F, Childs J, Rodriguez-Ortiz CJ, Garcia-Leon JA, Kitazawa M, Shahnawaz M, Matheos DP, Ma X, Cunha CD, Walls KC, Ager RR, Soto C, Gutierrez A, Moreno-Gonzalez I, Mortazavi A, Tenner AJ, MacGregor GR, Wood M, Green KN, LaFerla FM (2021) Generation of a humanized aβ expressing mouse demonstrating aspects of Alzheimer’s disease-like pathology
Nature Communications

Naciri I, Lin B, Webb CH, Jiang S, Carmona S, Liu W, Mortazavi A, Sun S (2021) Linking Chromosomal Silencing with Xist Expression from Autosomal Integrated Transgenes
Frontiers in Cell and Developmental Biology

Balderrama-Gutierrez G, Milovic A, Cook VJ, Islam MN, Zhang Y, Kiaris H, Belisle JT, Mortazavi A, Barbour AG (2021) An Infection-Tolerant Mammalian Reservoir for Several Zoonotic Agents Broadly Counters the Inflammatory Effects of Endotoxin
mBio

Chau, J., Kong, X., Nguyen, N. V., Williams, K., Tawil, R., Kiyono, T., Mortazavi A, Yokomori, K (2021) Relationship of DUX4 and target gene expression in FSHD myocytes
Human Mutation

Bolton JL, Schulmann A, Garcia-Curran MM, Regev L, Chen Y, Kamei N, Shao M, Singh-Taylor A, Jiang S, Noam Y, Molet J, Mortazavi A, Baram TZ (2020) Unexpected Transcriptional Program Contribute to Hipppocampal Memory Deficits and Neuronal Stunting after Early-Life Adversity
Cell Reports

Oblak AL, Forner S, Territo PR, Sasner M, Carter GW, Howell GR, Sukoff-Rizzo SJ, Logsdon BA, Mangravite LM, Mortazavi A, Baglietto-Vargas D, Green KN, MacGregor GR, Wood MA, Tenner AJ, LaFerla FM, Lamb BT, The MODEL-AD (2020) Model organism development and evaluation for late-onset Alzheimer’s disease: MODEL-AD
Translational Research & Clinical Interventions

Hultgren NW, Fang JS, Ziegler ME, Ramirez RN, Phan DT, Hatch M, Welch-Reardon KM, Paniagua AE, Kim LS, Shon NN, Williams DS, Mortazavi A, Hughes CW (2020) Slug regulates the Dll4-Notch-VEGFR2 axis to control endothelial cell activation and angiogenesis
Nature Communications

Reese F, Mortazavi, A (2020) Swan: a library for the analysis and visualization of long-read transcriptomes
Bioinformatics

Chang D, Serra L, Lu D, Mortazavi, A, Dillman A (2020) A revised Adaptation of the Smart-seq2 Protocol for Single-Nematode RNA-Seq
RNA Abundance Analysis

ENCODE Project Consortium (2020) Expanded encyclopedias of DNA elements in the human and mouse genomes
Nature

Partridge EC, Chhetri SB, Prokop JW, Ramaker RC, Jansen CS, Goh ST, Mackiewicz M, Newberry KM, Brandsmeier LA, Meadows SK, Messer CL, Hardigan AA, Coppola CJ, Dean EC, Jiang S, Savic D, Mortazavi, A, Wold BJ, Myers RM, Mendenhall EM (2020) Occupancy maps of 208 chromatin-associated proteins in one human cell type
Nature

Jiang S, Williams K, Kong X, Zeng W, Nguyen NV, Ma X, Tawil R, Yokomori K, Mortazavi, A (2020) Single-nucleus RNA-seq identifies divergent populations of FSHD2 myotube nuclei
PLoS Genetics

Macias-Munoz A, Murad R, Mortazavi, A (2019) Molecular evolution and expression of opsin genes in Hydra vulgaris
BMC Genomics

Jansen C, Ramirez RN, El-Ali NC, Gomez-Cabrero D, Tegner J, Merkenschlager M, Conesa A, Mortazavi, A (2019) Building gene regulatory networks from scATAC-seq and scRNA-seq using Linked Self Organizing Maps
PLoS Computational Biology

Gomez-Cabrero D., Tarazona S., Ferreirós-Vidal I., Ramirez R.N., Company C., Schmidt A, Reijmers T, Paul VVS, Marabita F, Rodríguez-Ubreva J, Garcia-Gomez A, Carroll T, Cooper L, Liang Z, Dharmalingam G, van der Kloet F, Harms AC, Balzano-Nogueira L, Lagani V, Tsamardinos I, Lappe M, Maier D, Westerhuis JA, Hankemeier T, Imhof A, Ballestar E, Mortazavi, A, Merkenschlager M, Tegner J, Conesa A (2019) STATegra, a comprehensive multi-omics dataset of B-cell differentiation in mouse
Scientific Data

Rahmanian S, Murad R, Breschi A, Zeng W, Mackiewicz M, Williams B, Davis CA, Roberts B, Meadows S, Moore D, Trout D, Zaleski C, Dobin A, Sei LH, Drenkow J, Scavelli A, Gingeras TR, Wold BJ, Myers RM, Guigó R, Mortazavi, A (2019) Dynamics of microRNA expression during mouse prenatal development
Genome Research

Mortazavi, A, Baram TZ (2019) Intra-individual changes in methylome profiles: an epigenetic ‘scar’ of early-life adversity ?
Neuropsychopharmacology

Long AD, Baldwin-Brown J, Tao Y, Cook VJ, Balderrama-Gutierrez G, Corbett-Detig R, Mortazavi A, Barbour AG (2019) The genome of Peromyscus leucopus, natural host for Lyme disease and other emerging infections
Science Advances

Jansen CS, Mortazavi, A (2019) Progressive Clustering and Characterization of Increasingly Higher Dimensional Datasets with Living Self-Organizing Maps
WSOM 2019

Serra L, Macchietto M, Macias-Muñoz A, McGill CJ, Rodriguez IM, Rodriguez B, Murad R, Mortazavi, A (2019) Hybrid assembly of the genome of the entomopathogenic nematode Steinernema carpocapsae identifies the X-chromosome
G3

Chang DZ, Serra L, Lu D, Mortazavi, A, Dillman AR (2019) A core set of venom proteins is released by entomopathogenic nematodes in the genus Steinernema
PLoS Pathogens

Fung L, Guzman H, Sevrioukov E, Idica A, Park E, Bochnakian A, Daugaard I, Jury D, Mortazavi, A, Zisoulis DG, Pedersen IM (2019) miR-128 Restriction of LINE-1 (L1) Retrotransposition is Dependent on Targeting hnRNPA1 mRNA
Int J Mol Sci

Ferreirós-Vidal I, Carroll T, Zhang T, Lagani V, Ramirez RN, Ing-Simmons E, Gómez-Valadés AG, Cooper L, Liang Z, Papoutsoglou G, Dharmalingam G, Guo Y, Tarazona S, Fernandes SJ, Noori P, Silberberg G, Fisher AG, Tsamardinos I, Mortazavi, A., Lenhard B, Conesa A, Tegner J, Merkenschlager M, Gomez-Cabrero D. (2019) Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation.
PLoS Biology

Jiang S, Kamei N, Bolton JL, Ma X, Stern HS, Baram TZ, Mortazavi A (2019) Intra-individual methylomics detects the impact of early-life adversity
Life Science Alliance

Najafi AR, Crapser J, Jiang, S, Ng W, Mortazavi, A, West BL, Green KN (2018) A limited capacity for microglial repopulation in the adult brain
Glia

Wyman DE, Mortazavi A (2018) TranscriptClean: Variant-aware correction of indels, mismatches and splice junctions in long-read transcripts
Bioinformatics

Nguyen K, Aggarwal MB, Feng C, Balderrama G, Fazio M, Mortazavi A, Spitale RC (2018) Spatially restricting biorthogonal nucleoside biosynthesis enables selective metabolic labeling of the mitochondrial transcriptome
ACS Chemical Biology

Jiang S, Mortazavi A (2018) Integrating ChIP-seq with other functional genomics data.
Briefings in Functional Genomics

Serra L, Chang DZ, Macchietto M, Williams K, Murad R, Lu D, Dillman AR, Mortazavi A (2018) Adapting the Smart-seq2 Protocol for Robust Single Worm RNA-seq.
Bio-protocol

Tardaguila M, de la Fuente L, Marti C, Pereira C, Pardo-Palacios FJ, del Risco H, Ferrell M, Mellado M, Macchietto M, Edelmann M, Ezkurdia I, Vazquez J, Tress M, Mortazavi A, Martens L, Rodriguez-Navarro S, Moreno-Manzano V, Conesa A (2018) SQANTI: extensive characterization of long-read transcript sequences for quality control in full-length transcriptome identification and quantification.
Genome Research

Sierra RA, Hoverter NP, Ramirez RN, Vuong LM, Mortazavi A, Merrill BJ, Waterman ML, Donovan PJ (2018) TCF7L1 suppresses primitive streak gene expression to support human embryonic stem cell pluripotency.
Development

Guerrero-Juarez CF, Astrowski, AA, Murad, R, Dang, CT, Shatrova, VO, Astrowskaja, A, Lim CH, Ramos R, Wang X, Liu Y, Lee HL, Pham KT, Hsi TC, Oh JW, Crocker D, Mortazavi A, Ito M, Plikus MV (2018) Wound regeneration deficit in rats correlates with low morphogenetic potential and distinct transcriptome profile of epidermis.
Journal of Investigative Dermatology

Rodríguez-Ubreva J, Català-Moll F, Obermajer N, Álvarez-Errico D, Ramirez RN, Company C, Vento-Tormo R, Moreno-Bueno G, Edwards RP, Mortazavi A, Kalinski P, Ballestar E (2017) Prostaglandin E2 Leads to the Acquisition of DNMT3A-Dependent Tolerogenic Functions in Human Myeloid-Derived Suppressor Cells.
Cell Reports

Macchietto M, Angdembey D, Heidarpour N, Rodriguez B, Serra L, El-Ali N, Mortazavi A (2017) Comparative transcriptomics of Steinernema and Caenorhabditis single embryos reveals orthologous gene expression convergence during late embryogenesis.
Genome Biology and Evolution

Hernandez MX, Jiang S, Cole TA, Chu SH, Fonseca MI, Fang MJ, Hohsfield LA, Torres MD, Green KN, Wetsel RA, Mortazavi A, Tenner AJ (2017) Prevention of C5aR1 signaling delays microglial inflammatory polarization, favors clearance pathways and suppresses cognitive loss.
Molecular Neurodegeneration

Longabaugh WJR, Zeng W, Zhang JA, Hosokawa H, Jansen CS, Li L, Romero-Wolf M, Liu P, Kueh HY, Mortazavi A, Rothenberg EV (2017) Bcl11b and combinatorial resolution of cell fate in the T-cell gene regulatory network.
PNAS

Lu D, Macchietto M, Chang D, Barros MM, Baldwin J, Mortazavi A, Dillman AR (2017) Activated entomopathogenic nematode infective juveniles release lethal venom proteins.
PLoS Pathogens

Abud EM, Ramirez RN, 17 authors, Mortazavi A, Carson MJ, Poon WW, Blurton-Jones M (2017) iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases.
Neuron

Ramirez RN, El-Ali NC, Mager MA, Wyman D, Conesa A, Mortazavi A (2017) Dynamic Gene Regulatory Networks of Human Myeloid Differentiation.
Cell Systems

Plikus MV, Guerrero-Juarez CF, …21 authors…, Ramirez RN, Murad R, Offermanns S, Metzger D, Chambon P, Widgerow AD, Tuan TL, Mortazavi A, Gupta RK, Hamilton BA, Millar SE, Seale P, Pear WS, Lazar MA, Cotsarelis G (2017) Regeneration of fat cells from myofibroblasts during wound healing. Science

Singh-Taylor A, Molet J, Jiang S, Korosi A, Bolton JL, Noam Y, Simeone K, Cope J, Chen Y, Mortazavi A, Baram TZ (2017) NRSF-dependent epigenetic mechanisms contribute to programming of stress-sensitive neurons by neonatal experience, promoting resilience.
Molecular Psychiatry

Zeng W, Jiang S, Kong X, El-Ali N, Ball AR Jr, MA CI, Hashimoto N, Yokomori K, Mortazavi A (2016) Single-nucleus RNA-seq of differentiating myoblasts reveals the extent of fate heterogeneity
Nucleic Acids Research

Conesa A, Madrigal P, Tarazona S, Gomez-Cabrero D, Cervera A, McPherson A, Szczesniak MW, Gaffney DJ, Elo LL, Zhang X, Mortazavi A (2016) A survey of best practices for RNA-seq data analysis.
Genome Biology

Dillman AR, Macchietto M, Porter CF, Rogers A, Williams B, Antoshechkin I, Lee MM, Goodwin Z, Lu X, Lewis EE, Goodrich-Blair H, Stock SP, Adams BJ, Sternberg PW, Mortazavi A (2015) Comparative genomics of Steinernema reveals deeply conserved gene regulatory networks.
Genome Biology

Mortazavi A (2015) Better together: multiplexing samples to improve the preparation and reliability of gene expression studies.
Nature Methods

Daniels EV, Murad R, Mortazavi A, Reed RD (2014) Extensive transcriptional response associated with seasonal plasticity of butterfly wing patterns.
Molecular Ecology

Yue F, ….60 authors …, Jansen C, …65 authors…, Mortazavi A, … 9 authors (2014) A comparative encyclopedia of DNA elements in the mouse genome.
Nature

Gerstein MB, Rozowsky J, … 56 authors…, Mortazavi A, Murad R, … 36 authors (2014) Comparative analysis of the transcriptome across distant species.
Nature

Zeng W, Chen YY, Newkirk DA, Wu B, Balog J, Kong X, Ball AR, Zanotti S, Tawil R, Hasimoto N, Mortazavi A, van der Maarel K, Yokomori K (2014) Genetic and Epigenetic Characteristics of FSHD-Associated 4q and 10q D4Z4 that are distinct from Non-4q/10q D4Z4 Homologs.
Human Mutation

Blanc V, Park E, Schaefer S, Miller M, Lin Y, Kennedy S, Billing AM, Hamidane HB, Graumann J, Mortazavi A, Nadeau JH, Davidson NO (2014) Genome-wide identification and functional analysis of Apobec-1-mediated C-to-U RNA editing in mouse small intestine and liver.
Genome Biology

Conesa A, Mortazavi A (2014) The common ground of genomics and systems biology.
BMC Systems Biology

Steijger T, Abril JF, Engström PG, Kokocinski F; The RGASP Consortium, Akerman M, Alioto T, Ambrosini G, Antonarakis SE, Behr J, Bertone P, Bohnert R, Bucher P, Cloonan N, Derrien T, Djebali S, Du J, Dudoit S, Gerstein M, Gingeras TR, Gonzalez D, Grimmond SM, Guigó R, Habegger L, Harrow J, Hubbard TJ, Iseli C, Jean G, Kahles A, Lagarde J, Leng J, Lefebvre G, Lewis S, Mortazavi A, and 26 more authors (2013) Assessment of transcript reconstruction methods for RNA-seq.
Nature Methods

Mortazavi A, Pepke S, Jansen C, Marinov GK, Ernst J, Kellis M, Hardison R, Myers RM, Wold B (2013) Integrating and mining the chromatin landscape of cell type specificity using Self-Organizing Maps.
Genome Research

Srinivasan J, Dilman AR, Macchietto MG, Heikkinen L, Lakso M, Fracchia KM, Antoshechkin I, Mortazavi A, Wong G, Sternberg PW (2013) The Draft Genome and Transcriptome of Panagrellus redivivus are shaped by the harsh demands of a free-living lifestyle.
Genetics

Park E, Williams B, Wold B, Mortazavi A (2012) RNA Editing in the human ENCODE RNA-seq data.
Genome Research.

The ENCODE Consortium (2012) An Integrated Encyclopedia of DNA Elements in the Human Genome.
Nature

Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, et al. (2012) Landscape of transcription in human cells.
Nature

Zeng W, Mortazavi A (2012) Technical considerations for functional sequencing assays.
Nature Immunology

The Mouse ENCODE Consortium (2012) An Encyclopedia of Mouse DNA Elements (Mouse ENCODE).
Genome Biology

Dilman AR, Mortazavi A, Sternberg PW (2012) Incorporating Genomics into the Toolkit of Nematology.
Journal of Nematology

Zhang JA, Mortazavi A, Williams BA, Wold BJ, Rothenberg EV (2012) Dynamic transformations of epigenetic marking and genome-wide transcriptional regulation establish T cell identity.
Cell

The ENCODE Project Consortium. (2011). A user's guide to the Encyclopedia of DNA Elements (ENCODE).
PLoS Biol.

Trapnell C, Williams BA, Porta G, Mortazavi A, Kwan G, van Baren MJ, Salzberg SL, Wold BJ, Pachter B. (2010) Transcript assembly and quantification by RNA-seq reveals unannotated transcripts and isoform switching during cell differentiation.
Nature Biotech

Mortazavi A*, Schwarz EM*, Williams B, Schaeffer L, Antoshechkin I, Wold BJ, Sternberg PW. (2010) Scaffolding a de novo nematode genome with RNA-seq.
Genome Research.

Pepke S, Wold B, Mortazavi A. (2009). Computation for ChIP-seq and RNA-seq studies.
Nature Methods.

Mortazavi A*, Williams BA*, McCue K, Schaeffer L, Wold B. (2008). Mapping and quantifying mammalian transcriptomes by RNA-seq.
Nature Methods.

Berghella L, De Angelis L, De Buysscher T, Mortazavi A, Biressi S, Forcales SV, Sirabella D, Cossu G, Wold BJ. (2008) A highly conserved molecular switch binds MSY-3 to regulate myogenin repression in postnatal muscle.
Genes and Development.

*Johnson, D. S., *Mortazavi, A., Myers, R. M. and Wold, B. (2007). Genome-wide mapping of in vivo protein DNA interactions.
Science. (*co-first authors).

Mortazavi A, Leeper Thompson EC, Garcia ST, Myers RM, Wold B. (2006). Comparative genomics modeling of the NRSF/REST repressor network: from single conserved sites to genome-wide repertoire.
Genome Research.

Roden JC, King BW, Trout D, Mortazavi A, Wold BJ, Hart CE. (2006). Mining gene expression data by interpreting principal components.
BMC Bioinformatics.

Professional Societies

Genetics Society of America
Society for Neuroscience

Other Experience

Associate Editor
BMC Bioinformatics 2010

Graduate Programs

Cellular and Molecular Biosciences
Mathematical and Computational Biology

Research Centers

Center for Complex Biological Systems