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. 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 Aug 01; 83(15):2527-2542.  View on PubMed
  2. 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
  3. 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
  4. 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
  5. Diaz AA. Loss of ATRX suppresses anti-tumor immunity. Neuro Oncol. 2022 06 01; 24(6):901-902.  View on PubMed
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. Diaz AA. Exosomal PD-L1 induces immunosuppressive nonclassical monocytes. Neuro Oncol. 2020 07 07; 22(7):901-902.  View on PubMed
  13. Wang L, Catalan F, Shamardani K, Babikir H, Diaz A. Ensemble learning for classifying single-cell data and projection across reference atlases. Bioinformatics. 2020 06 01; 36(11):3585-3587.  View on PubMed
  14. 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. Clonal ZEB1-Driven Mesenchymal Transition Promotes Targetable Oncologic Antiangiogenic Therapy Resistance. Cancer Res. 2020 04 01; 80(7):1498-1511.  View on PubMed
  15. 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, Nowakowski TJ, Lim DA, Diaz A, Raleigh DR, Kriegstein AR. Outer Radial Glia-like Cancer Stem Cells Contribute to Heterogeneity of Glioblastoma. Cell Stem Cell. 2020 01 02; 26(1):48-63.e6.  View on PubMed
  16. 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. The Phenotypes of Proliferating Glioblastoma Cells Reside on a Single Axis of Variation. Cancer Discov. 2019 12; 9(12):1708-1719.  View on PubMed
  17. 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 Jul 17; 103(2):349.  View on PubMed
  18. 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 07 17; 103(2):309-322.e7.  View on PubMed
  19. 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. The immune suppressive microenvironment of human gliomas depends on the accumulation of bone marrow-derived macrophages in the center of the lesion. J Immunother Cancer. 2019 02 27; 7(1):58.  View on PubMed
  20. 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 09 15; 34(18):3217-3219.  View on PubMed

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