Aaron Diaz, PhD
Associate Professor
Neurological Surgery
School of Medicine

However, in highly diverse tumors, such as gliomas, clinical trials of promising targeted therapeutics often produce mixed results. This is at least partially due to intra-tumor regional heterogeneity in response to treatment. To address this pressing challenge, we combine high-throughput single-cell sequencing with state-of-the-art machine-learning algorithms, to produce quantitative models of tumor heterogeneity and micro-environment interaction. Moreover, brain tumor cells can exhibit phenotypes, and molecular signatures, of cell types found in the developing brain. We are also interested in the role of early-brain developmental programs in brain tumor growth.

• Tumor-wide RNA splicing aberrations generate immunogenic public neoantigens.
  bioRxiv : the preprint server for biology 2023 Kwok DW, Stevers NO, Nejo T, Chen LH, Etxeberria I, Jung J, Okada K, Cove MC, Lakshmanachetty S, Gallus M, Barpanda A, Hong C, Chan GKL, Wu SH, Ramos E, Yamamichi A, Liu J, Watchmaker P, Ogino H, …
• PP2Ac Deficiency Enhances Tumor Immunogenicity by Activating STING-Type I Interferon Signaling in Glioblastoma.
  Cancer research 2023 Mondal I, Das O, Sun R, Gao J, Yu B, Diaz A, Behnan J, Dubey A, Meng Z, Eskandar E, Xu B, Lu RO, Ho WS
• Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects.
  The Journal of clinical investigation 2023 Jain S, Rick JW, Joshi RS, Beniwal A, Spatz J, Gill S, Chang AC, Choudhary N, Nguyen AT, Sudhir S, Chalif EJ, Chen JS, Chandra A, Haddad AF, Wadhwa H, Shah SS, Choi S, Hayes JL, Wang L, Yagnik G, …
• A single-cell atlas of glioblastoma evolution under therapy reveals cell-intrinsic and cell-extrinsic therapeutic targets.
  Nature cancer 2022 Wang L, Jung J, Babikir H, Shamardani K, Jain S, Feng X, Gupta N, Rosi S, Chang S, Raleigh D, Solomon D, Phillips JJ, Diaz AA
• The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location.
  Nature genetics 2022 Liu I, Jiang L, Samuelsson ER, Marco Salas S, Beck A, Hack OA, Jeong D, Shaw ML, Englinger B, LaBelle J, Mire HM, Madlener S, Mayr L, Quezada MA, Trissal M, Panditharatna E, Ernst KJ, Vogelzang J, …
• Discovering dominant tumor immune archetypes in a pan-cancer census.
  Cell 2021 Combes AJ, Samad B, Tsui J, Chew NW, Yan P, Reeder GC, Kushnoor D, Shen A, Davidson B, Barczak AJ, Adkisson M, Edwards A, Naser M, Barry KC, Courau T, Hammoudi T, Argüello RJ, Rao AA, Olshen AB, …
• TIGIT and PD-1 Immune Checkpoint Pathways Are Associated With Patient Outcome and Anti-Tumor Immunity in Glioblastoma.
  Frontiers in immunology 2021 Raphael I, Kumar R, McCarl LH, Shoger K, Wang L, Sandlesh P, Sneiderman CT, Allen J, Zhai S, Campagna ML, Foster A, Bruno TC, Agnihotri S, Hu B, Castro BA, Lieberman FS, Broniscer A, Diaz AA, …
• miRNA-independent function of long noncoding pri-miRNA loci.
  Proceedings of the National Academy of Sciences of the United States of America 2021 He D, Wu D, Muller S, Wang L, Saha P, Ahanger SH, Liu SJ, Cui M, Hong SJ, Jain M, Olson HE, Akeson M, Costello JF, Diaz A, Lim DA
• Unique challenges for glioblastoma immunotherapy-discussions across neuro-oncology and non-neuro-oncology experts in cancer immunology. Meeting Report from the 2019 SNO Immuno-Oncology Think Tank.
  Neuro-oncology 2021 Chuntova P, Chow F, Watchmaker PB, Galvez M, Heimberger AB, Newell EW, Diaz A, DePinho RA, Li MO, Wherry EJ, Mitchell D, Terabe M, Wainwright DA, Berzofsky JA, Herold-Mende C, Heath JR, Lim M, …
• The evolution of alternative splicing in glioblastoma under therapy.
  Genome biology 2021 Wang L, Shamardani K, Babikir H, Catalan F, Nejo T, Chang S, Phillips JJ, Okada H, Diaz AA
• Exosomal PD-L1 induces immunosuppressive nonclassical monocytes.
  Neuro-oncology 2020 Diaz AA
• Ensemble learning for classifying single-cell data and projection across reference atlases.
  Bioinformatics (Oxford, England) 2020 Wang L, Catalan F, Shamardani K, Babikir H, Diaz A
• Clonal ZEB1-Driven Mesenchymal Transition Promotes Targetable Oncologic Antiangiogenic Therapy Resistance.
  Cancer research 2020 Chandra A, Jahangiri A, Chen W, Nguyen AT, Yagnik G, Pereira MP, Jain S, Garcia JH, Shah SS, Wadhwa H, Joshi RS, Weiss J, Wolf KJ, Lin JG, Müller S, Rick JW, Diaz AA, Gilbert LA, Kumar S, Aghi MK
• Outer Radial Glia-like Cancer Stem Cells Contribute to Heterogeneity of Glioblastoma.
  Cell stem cell 2020 Bhaduri A, Di Lullo E, Jung D, Müller S, Crouch EE, Espinosa CS, Ozawa T, Alvarado B, Spatazza J, Cadwell CR, Wilkins G, Velmeshev D, Liu SJ, Malatesta M, Andrews MG, Mostajo-Radji MA, Huang EJ, …
• The Phenotypes of Proliferating Glioblastoma Cells Reside on a Single Axis of Variation.
  Cancer discovery 2019 Wang L, Babikir H, Müller S, Yagnik G, Shamardani K, Catalan F, Kohanbash G, Alvarado B, Di Lullo E, Kriegstein A, Shah S, Wadhwa H, Chang SM, Phillips JJ, Aghi MK, Diaz AA
• Thermoregulation via Temperature-Dependent PGD2 Production in Mouse Preoptic Area.
  Neuron 2019 Wang TA, Teo CF, Åkerblom M, Chen C, Tynan-La Fontaine M, Greiner VJ, Diaz A, McManus MT, Jan YN, Jan LY
• Thermoregulation via Temperature-Dependent PGD2 Production in Mouse Preoptic Area.
  Neuron 2019 Wang TA, Teo CF, Åkerblom M, Chen C, Tynan-La Fontaine M, Greiner VJ, Diaz A, McManus MT, Jan YN, Jan LY
• The immune suppressive microenvironment of human gliomas depends on the accumulation of bone marrow-derived macrophages in the center of the lesion.
  Journal for immunotherapy of cancer 2019 Pinton L, Masetto E, Vettore M, Solito S, Magri S, D'Andolfi M, Del Bianco P, Lollo G, Benoit JP, Okada H, Diaz A, Della Puppa A, Mandruzzato S
• CONICS integrates scRNA-seq with DNA sequencing to map gene expression to tumor sub-clones.
  Bioinformatics (Oxford, England) 2018 Müller S, Cho A, Liu SJ, Lim DA, Diaz A
• CONICS integrates scRNA-seq with DNA sequencing to map gene expression to tumor sub-clones
  Bioinformatics 2018 S. Müller, A. Cho, S. Liu, D. Lim, A. Diaz
• Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas.
  JCI insight 2018 Müller S, Agnihotri S, Shoger KE, Myers MI, Smith N, Chaparala S, Villanueva CR, Chattopadhyay A, Lee AV, Butterfield LH, Diaz A, Okada H, Pollack IF, Kohanbash G
• The Transcriptionally Permissive Chromatin State of Embryonic Stem Cells Is Acutely Tuned to Translational Output.
  Cell stem cell 2018 Bulut-Karslioglu A, Macrae TA, Oses-Prieto JA, Covarrubias S, Percharde M, Ku G, Diaz A, McManus MT, Burlingame AL, Ramalho-Santos M
• Single-cell profiling of human gliomas reveals macrophage ontogeny as a basis for regional differences in macrophage activation in the tumor microenvironment.
  Genome biology 2017 Müller S, Kohanbash G, Liu SJ, Alvarado B, Carrera D, Bhaduri A, Watchmaker PB, Yagnik G, Di Lullo E, Malatesta M, Amankulor NM, Kriegstein AR, Lim DA, Aghi M, Okada H, Diaz A
• Single-cell Co-expression Subnetwork Analysis.
  Scientific reports 2017 Bartlett TE, Müller S, Diaz A
• Single-Cell mRNA Sequencing in Cancer Research: Integrating the Genomic Fingerprint.
  Frontiers in genetics 2017 Müller S, Diaz A
• Single-cell sequencing maps gene expression to mutational phylogenies in PDGF- and EGF-driven gliomas.
  Molecular systems biology 2016 Müller S, Liu SJ, Di Lullo E, Malatesta M, Pollen AA, Nowakowski TJ, Kohanbash G, Aghi M, Kriegstein AR, Lim DA, Diaz A
• SCell: integrated analysis of single-cell RNA-seq data.
  Bioinformatics (Oxford, England) 2016 Diaz A, Liu SJ, Sandoval C, Pollen A, Nowakowski TJ, Lim DA, Kriegstein A
• Single-cell analysis of long non-coding RNAs in the developing human neocortex.
  Genome biology 2016 Liu SJ, Nowakowski TJ, Pollen AA, Lui JH, Horlbeck MA, Attenello FJ, He D, Weissman JS, Kriegstein AR, Diaz AA, Lim DA
• A gene-expression screen identifies a non-toxic sumoylation inhibitor that mimics SUMO-less human LRH-1 in liver.
  eLife 2015 Suzawa M, Miranda DA, Ramos KA, Ang KK, Faivre EJ, Wilson CG, Caboni L, Arkin MR, Kim YS, Fletterick RJ, Diaz A, Schneekloth JS, Ingraham HA
• Molecular identity of human outer radial glia during cortical development.
  Cell 2015 Pollen AA, Nowakowski TJ, Chen J, Retallack H, Sandoval-Espinosa C, Nicholas CR, Shuga J, Liu SJ, Oldham MC, Diaz A, Lim DA, Leyrat AA, West JA, Kriegstein AR
• HiTSelect: a comprehensive tool for high-complexity-pooled screen analysis.
  Nucleic acids research 2014 Diaz AA, Qin H, Ramalho-Santos M, Song JS
• Recurrent epimutations activate gene body promoters in primary glioblastoma.
  Genome research 2014 Nagarajan RP, Zhang B, Bell RJ, Johnson BE, Olshen AB, Sundaram V, Li D, Graham AE, Diaz A, Fouse SD, Smirnov I, Song J, Paris PL, Wang T, Costello JF
• Integration of genome-wide approaches identifies lncRNAs of adult neural stem cells and their progeny in vivo.
  Cell stem cell 2013 Ramos AD, Diaz A, Nellore A, Delgado RN, Park KY, Gonzales-Roybal G, Oldham MC, Song JS, Lim DA
• NSeq: a multithreaded Java application for finding positioned nucleosomes from sequencing data.
  Frontiers in genetics 2013 Nellore A, Bobkov K, Howe E, Pankov A, Diaz A, Song JS
• CHANCE: comprehensive software for quality control and validation of ChIP-seq data.
  Genome biology 2012 Diaz A, Nellore A, Song JS
• Genome Biology
  CHANCE: comprehensive software for quality control and validation of ChIP-seq data 2012 Diaz A, Nellore A, Song J S
• Normalization, bias correction, and peak calling for ChIP-seq.
  Statistical applications in genetics and molecular biology 2012 Diaz A, Park K, Lim DA, Song JS
• Polycomb-like 3 promotes polycomb repressive complex 2 binding to CpG islands and embryonic stem cell self-renewal.
  PLoS genetics 2012 Hunkapiller J, Shen Y, Diaz A, Cagney G, McCleary D, Ramalho-Santos M, Krogan N, Ren B, Song JS, Reiter JF
• Proceedings of the 4th WSEAS/IASME International Conference on Dynamical Systems and Control
  Rezoning Techniques for ALE Computations 2008 Diaz A
• Nonlinear Analysis: Hybrid Systems
  An Error Analysis for Execution Traces of Hybrid Automata Using Jacobi's Equation 2008 Diaz, A
• European Series in Applied and Industrial Mathematics: Proceedings Societe de Mathematiques Appliquees et Industrielles
  A Cell-Centered Arbitrary Lagrangian Eulerian (ALE) Method for Multimaterial Compressible Flows 2008 Maire P-H, De Buhan M, Diaz A, Dobrzynski C, Kluth G, Lagoutiere, F
• International Journal of Hybrid Systems
  Extraction of Finite State Controllers, AD and DA maps, and Associated Small Topologies for Measure Valued Control Laws 2003 Diaz A