Research Summary

The Diaz Lab is interested in developing targeted therapeutics for the treatment of glioma. We apply molecular and computational approaches to elucidate targets and pathways mediating cancer progression. To date, some of the most effective cancer therapies have been those that hone in on molecular defects associated with specific driver genes. 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.

Research Funding

  • July 1, 2022 - June 30, 2026 - An informatics framework for single-cell multi-omics from clinical specimens , PI . Sponsor: NIH/NLM, Sponsor Award ID: R01LM013897
  • September 1, 2018 - May 30, 2024 - PROJECT HOPE: “High-Grade Glioma-Omics in Pediatric and AYA” , Project PI . Sponsor: NIH/NCI, Sponsor Award ID: P30 CA 82103
  • July 1, 2022 - June 30, 2023 - Decoding the epigenetic differences between molecular subtypes of pediatric diffuse midline glioma , Project PI . Sponsor: NIH/NCI, Sponsor Award ID: P30 CA 82103
  • July 1, 2019 - June 30, 2023 - Oncolytic virus to potentiate immune-checkpoint blockade in immunologically cold brain tumors , PI . Sponsor: Department of Defense, Sponsor Award ID: W81XWH-19-1-0348

Education

New York University, New York, NY, BA, 05/97, Mathematics
Cornell University, Ithaca, NY, MS, 05/03, Computer Science
Cornell University, Ithaca, NY, PhD, 05/03, Applied Mathematics

Honors & Awards

  • 2016, 2020
    Adult Basic Research Award, Society for Neuro-Oncology
  • 2015
    Brain Tumor SPORE Career Development Award, UCSF
  • 2010
    BCATS Plenary Talk Award
  • 2008
    Santa Clara University, Dean's Grant: “Implementing Eigenvalue Perturbation Techniques in Parallel.”
  • 1997
    Cornell University, Sage Fellowship and Engineering Scholarship.
  • 1997
    Institute for Advanced Study, Institute for Geometry and Topology Award.
  • 1993
    New York University, Tuition Scholarship

Selected Publications

  1. Kwok DW, Stevers NO, Etxeberria I, Nejo T, Colton Cove M, Chen LH, Jung J, Okada K, Lakshmanachetty S, Gallus M, Barpanda A, Hong C, Chan GKL, Liu J, Wu SH, Ramos E, Yamamichi A, Watchmaker PB, Ogino H, Saijo A, Du A, Grishanina NR, Woo J, Diaz A, Hervey-Jumper SL, Chang SM, Phillips JJ, Wiita AP, Klebanoff CA, Costello JF, Okada H. Tumour-wide RNA splicing aberrations generate actionable public neoantigens. Nature. 2025 Feb 19.  View on PubMed
  2. Lucas CG, Al-Adli NN, Young JS, Gupta R, Morshed RA, Wu J, Ravindranathan A, Shai A, Oberheim Bush NA, Taylor JW, de Groot J, Villanueva-Meyer JE, Pekmezci M, Perry A, Bollen AW, Theodosopoulos PV, Aghi MK, Chang EF, Hervey-Jumper SL, Raleigh DR, Molinaro AM, Costello JF, Diaz AA, Clarke JL, Butowski NA, Phillips JJ, Chang SM, Berger MS, Solomon DA. Longitudinal multimodal profiling of IDH-wildtype glioblastoma reveals the molecular evolution and cellular phenotypes underlying prognostically different treatment responses. Neuro Oncol. 2025 Jan 12; 27(1):89-105.  View on PubMed
  3. Lad M, Beniwal AS, Jain S, Shukla P, Kalistratova V, Jung J, Shah SS, Yagnik G, Saha A, Sati A, Babikir H, Nguyen AT, Gill S, Rios J, Young JS, Lui A, Salha D, Diaz A, Aghi MK. Glioblastoma induces the recruitment and differentiation of dendritic-like "hybrid" neutrophils from skull bone marrow. Cancer Cell. 2024 Sep 09; 42(9):1549-1569.e16.  View on PubMed
  4. Pichol-Thievend C, Anezo O, Pettiwala AM, Bourmeau G, Montagne R, Lyne AM, Guichet PO, Deshors P, Ballestín A, Blanchard B, Reveilles J, Ravi VM, Joseph K, Heiland DH, Julien B, Leboucher S, Besse L, Legoix P, Dingli F, Liva S, Loew D, Giani E, Ribecco V, Furumaya C, Marcos-Kovandzic L, Masliantsev K, Daubon T, Wang L, Diaz AA, Schnell O, Beck J, Servant N, Karayan-Tapon L, Cavalli FMG, Seano G. VC-resist glioblastoma cell state: vessel co-option as a key driver of chemoradiation resistance. Nat Commun. 2024 Apr 29; 15(1):3602.  View on PubMed
  5. Nejo T, Wang L, Leung KK, Wang A, Lakshmanachetty S, Gallus M, Kwok DW, Hong C, Chen LH, Carrera DA, Zhang MY, Stevers NO, Maldonado GC, Yamamichi A, Watchmaker PB, Naik A, Shai A, Phillips JJ, Chang SM, Wiita AP, Wells JA, Costello JF, Diaz AA, Okada H. Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma. Sci Rep. 2024 03 16; 14(1):6362.  View on PubMed
  6. Nejo T, Wang L, Leung KK, Wang A, Lakshmanachetty S, Gallus M, Kwok DW, Hong C, Chen LH, Carrera DA, Zhang MY, Stevers NO, Maldonado GC, Yamamichi A, Watchmaker P, Naik A, Shai A, Phillips JJ, Chang SM, Wiita AP, Wells JA, Costello JF, Diaz AA, Okada H. Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma. bioRxiv. 2023 Nov 02.  View on PubMed
  7. 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, Saijo A, Du A, Grishanina N, Woo J, Diaz A, Chang SM, Phillips JJ, Wiita AP, Klebanoff CA, Costello JF, Okada H. Tumor-wide RNA splicing aberrations generate immunogenic public neoantigens. bioRxiv. 2023 Oct 20.  View on PubMed
  8. 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. PP2Ac Deficiency Enhances Tumor Immunogenicity by Activating STING-Type I Interferon Signaling in Glioblastoma. Cancer Res. 2023 08 01; 83(15):2527-2542.  View on PubMed
  9. Lad BM, Beniwal AS, Jain S, Shukla P, Jung J, Shah SS, Yagnik G, Babikir H, Nguyen AT, Gill S, Young JS, Lui A, Salha D, Diaz A, Aghi MK. Glioblastoma induces the recruitment and differentiation of hybrid neutrophils from skull bone marrow. bioRxiv. 2023 Mar 25.  View on PubMed
  10. 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, Costello JF, Diaz A, Heiland DH, Aghi MK. Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects. J Clin Invest. 2023 03 01; 133(5).  View on PubMed
  11. 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. A single-cell atlas of glioblastoma evolution under therapy reveals cell-intrinsic and cell-extrinsic therapeutic targets. Nat Cancer. 2022 12; 3(12):1534-1552.  View on PubMed
  12. 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, Gatesman TA, Halbert ME, Palova H, Pokorna P, Sterba J, Slaby O, Geyeregger R, Diaz A, Findlay IJ, Dun MD, Resnick A, Suvà ML, Jones DTW, Agnihotri S, Svedlund J, Koschmann C, Haberler C, Czech T, Slavc I, Cotter JA, Ligon KL, Alexandrescu S, Yung WKA, Arrillaga-Romany I, Gojo J, Monje M, Nilsson M, Filbin MG. The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location. Nat Genet. 2022 12; 54(12):1881-1894.  View on PubMed
  13. Diaz AA. Loss of ATRX suppresses anti-tumor immunity. Neuro Oncol. 2022 06 01; 24(6):901-902.  View on PubMed
  14. 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, Immunoprofiler Consortium, Cai C, Zhan J, Davis KC, Kelley RK, Chapman JS, Atreya CE, Patel A, Daud AI, Ha P, Diaz AA, Kratz JR, Collisson EA, Fragiadakis GK, Erle DJ, Boissonnas A, Asthana S, Chan V, Krummel MF. Discovering dominant tumor immune archetypes in a pan-cancer census. Cell. 2022 01 06; 185(1):184-203.e19.  View on PubMed
  15. Babikir H, Wang L, Shamardani K, Catalan F, Sudhir S, Aghi MK, Raleigh DR, Phillips JJ, Diaz AA. ATRX regulates glial identity and the tumor microenvironment in IDH-mutant glioma. Genome Biol. 2021 11 11; 22(1):311.  View on PubMed
  16. 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, Amankulor NM, Rajasundaram D, Pollack IF, Kohanbash G. TIGIT and PD-1 Immune Checkpoint Pathways Are Associated With Patient Outcome and Anti-Tumor Immunity in Glioblastoma. Front Immunol. 2021; 12:637146.  View on PubMed
  17. 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. miRNA-independent function of long noncoding pri-miRNA loci. Proc Natl Acad Sci U S A. 2021 03 30; 118(13).  View on PubMed
  18. 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, Margolin KA, Chiocca EA, Kasahara N, Ellingson BM, Brown CE, Chen Y, Fecci PE, Reardon DA, Dunn GP, Liau LM, Costello JF, Wick W, Cloughesy T, Timmer WC, Wen PY, Prins RM, Platten M, Okada H. 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 Oncol. 2021 03 25; 23(3):356-375.  View on PubMed
  19. Wang L, Shamardani K, Babikir H, Catalan F, Nejo T, Chang S, Phillips JJ, Okada H, Diaz AA. The evolution of alternative splicing in glioblastoma under therapy. Genome Biol. 2021 01 26; 22(1):48.  View on PubMed
  20. Diaz AA. Exosomal PD-L1 induces immunosuppressive nonclassical monocytes. Neuro Oncol. 2020 07 07; 22(7):901-902.  View on PubMed

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