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Timothy Shaw, PhD

Program: Biostatistics and Bioinformatics

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Overview

Dr. Shaw's research focuses on systems immuno-oncology, particularly in developing computational tools to study immune interactions and associated regulatory networks.  


Associations

    • Biostatistics and Bioinformatics
    • Immuno-Oncology

Education & Training

Research

  Immunotherapy is emerging as a therapeutic modality, but achieving a durable response remains challenging in many instances. The problem is likely multifactorial and compounded by the complex regulatory network of the immune system. Thus, my research program aims to develop computational methodologies and tools to model these complexities. My program consists of the following three aims: 1) Building an integrative regulatory network of cancer-to-immune interactions and immune suppression. 2) Identifying targetable regulators generated from aim 1. 3) Using a proteo-genomics approach to identify cancer-specific isoforms for immunotherapy. My program will build a comprehensive systems biology resource of immune regulation of cancer, which will leverage multi-omics information derived from hidden-driver analysis, kinase activity, protein isoforms, and protein-protein interactions. Such an integrative approach presents opportunities to identify targets for immunotherapy or other therapeutic intervention.  

Publications

  • Shaw TI, Dong L, Tian L, Qian C, Liu Y, Ju B, High A, Kavdia K, Pagala VR, Shaner B, Pei D, Easton J, Janke LJ, Porter SN, Ma X, Cheng C, Pruett-Miller SM, Choi J, Yu J, Peng J, Gu W, Look AT, Downing JR, Zhang J. Integrative network analysis reveals USP7 haploinsufficiency inhibits E-protein activity in pediatric T-lineage acute lymphoblastic leukemia (T-ALL). Sci Rep. 2021 Mar.11(1):5154. Pubmedid: 33664368. Pmcid: PMC7933146.
  • Wagner J, Wickman E, Shaw TI, Anido AA, Langfitt D, Zhang J, Porter SN, Pruett-Miller SM, Tillman H, Krenciute G, Gottschalk S. Antitumor Effects of CAR T Cells Redirected to the EDB Splice Variant of Fibronectin. Cancer Immunol Res. 2021 Mar.9(3):279-290. Pubmedid: 33355188. Pmcid: PMC7925432.
  • Haydar D, Houke H, Chiang J, Yi Z, Odé Z, Caldwell K, Zhu X, Mercer KS, Stripay JL, Shaw TI, Vogel P, DeRenzo C, Baker SJ, Roussel MF, Gottschalk S, Krenciute G. Cell-surface antigen profiling of pediatric brain tumors: B7-H3 is consistently expressed and can be targeted via local or systemic CAR T-cell delivery. Neurooncol. 2021 Jun.23(6):999-1011. Pubmedid: 33320196. Pmcid: PMC8168826.
  • Ganguly S, Finkelstein D, Shaw TI, Michalek RD, Zorn KM, Ekins S, Yasuda K, Fukuda Y, Schuetz JD, Mukherjee K, Schuetz EG. Metabolomic and transcriptomic analysis reveals endogenous substrates and metabolic adaptation in rats lacking Abcg2 and Abcb1a transporters. PLoS One. 2021 Jul.16(7):e0253852. Pubmedid: 34255797. Pmcid: PMC8277073.
  • Wang X, Cho JH, Poudel S, Li Y, Jones DR, Shaw TI, Tan H, Xie B, Peng J. JUMPm: A Tool for Large-Scale Identification of Metabolites in Untargeted Metabolomics. Metabolites. 2020 May.10(5). Pubmedid: 32408578. Pmcid: PMC7281133.
  • Brewer CT, Kodali K, Wu J, Shaw TI, Peng J, Chen T. Toxicoproteomic Profiling of hPXR Transgenic Mice Treated with Rifampicin and Isoniazid. Cells. 2020 Jul.9(7). Pubmedid: 32660103. Pmcid: PMC7407182.
  • Glenn TC, Pierson TW, Bayona-Vásquez NJ, Kieran TJ, Hoffberg SL, Thomas Iv JC, Lefever DE, Finger JW, Gao B, Bian X, Louha S, Kolli RT, Bentley KE, Rushmore J, Wong K, Shaw TI, Rothrock MJ, McKee AM, Guo TL, Mauricio R, Molina M, Cummings BS, Lash LH, Lu K, Gilbert GS, Hubbell SP, Faircloth BC. Adapterama II: universal amplicon sequencing on Illumina platforms (TaggiMatrix). PeerJ. 2019 Oct.7:e7786. Pubmedid: 31616589. Pmcid: PMC6791344.
  • Wang B, Maxwell BA, Joo JH, Gwon Y, Messing J, Mishra A, Shaw TI, Ward AL, Quan H, Sakurada SM, Pruett-Miller SM, Bertorini T, Vogel P, Kim HJ, Peng J, Taylor JP, Kundu M. ULK1 and ULK2 Regulate Stress Granule Disassembly Through Phosphorylation and Activation of VCP/p97. Mol Cell. 2019 May.74(4):742-757.e8. Pubmedid: 30979586. Pmcid: PMC6859904.
  • Silveira AB, Kasper LH, Fan Y, Jin H, Wu G, Shaw TI, Zhu X, Larson JD, Easton J, Shao Y, Yergeau DA, Rosencrance C, Boggs K, Rusch MC, Ding L, Zhang J, Finkelstein D, Noyes RM, Russell BL, Xu B, Broniscer A, Wetmore C, Pounds SB, Ellison DW, Zhang J, Baker SJ. Correction to: H3.3 K27M depletion increases differentiation and extends latency of diffuse intrinsic pontine glioma growth in vivo. Acta Neuropathol. 2019 Jun.137(6):1021. Pubmedid: 30976974. Pmcid: PMC6999025.
  • Hunt LC, Stover J, Haugen B, Shaw TI, Li Y, Pagala VR, Finkelstein D, Barton ER, Fan Y, Labelle M, Peng J, Demontis F. A Key Role for the Ubiquitin Ligase UBR4 in Myofiber Hypertrophy in Drosophila and Mice. Cell Rep. 2019 Jul.28(5):1268-1281.e6. Pubmedid: 31365869. Pmcid: PMC6697171.
  • Xu K, Ding L, Chang TC, Shao Y, Chiang J, Mulder H, Wang S, Shaw TI, Wen J, Hover L, McLeod C, Wang YD, Easton J, Rusch M, Dalton J, Downing JR, Ellison DW, Zhang J, Baker SJ, Wu G. Structure and evolution of double minutes in diagnosis and relapse brain tumors. Acta Neuropathol. 2019 Jan.137(1):123-137. Pubmedid: 30267146. Pmcid: PMC6338707.
  • Wang H, Diaz AK, Shaw TI, Li Y, Niu M, Cho JH, Paugh BS, Zhang Y, Sifford J, Bai B, Wu Z, Tan H, Zhou S, Hover LD, Tillman HS, Shirinifard A, Thiagarajan S, Sablauer A, Pagala V, High AA, Wang X, Li C, Baker SJ, Peng J. Deep multiomics profiling of brain tumors identifies signaling networks downstream of cancer driver genes. Nat Commun. 2019 Aug.10(1):3718. Pubmedid: 31420543. Pmcid: PMC6697699.
  • Silveira AB, Kasper LH, Fan Y, Jin H, Wu G, Shaw TI, Zhu X, Larson JD, Easton J, Shao Y, Yergeau DA, Rosencrance C, Boggs K, Rusch MC, Ding L, Zhang J, Finkelstein D, Noyes RM, Russell BL, Xu B, Broniscer A, Wetmore C, Pounds SB, Ellison DW, Zhang J, Baker SJ. H3.3 K27M depletion increases differentiation and extends latency of diffuse intrinsic pontine glioma growth in vivo. Acta Neuropathol. 2019 Apr.137(4):637-655. Pubmedid: 30770999. Pmcid: PMC6546611.
  • Larson JD, Kasper LH, Paugh BS, Jin H, Wu G, Kwon CH, Fan Y, Shaw TI, Silveira AB, Qu C, Xu R, Zhu X, Zhang J, Russell HR, Peters JL, Finkelstein D, Xu B, Lin T, Tinkle CL, Patay Z, Onar-Thomas A, Pounds SB, McKinnon PJ, Ellison DW, Zhang J, Baker SJ. Histone H3.3 K27M Accelerates Spontaneous Brainstem Glioma and Drives Restricted Changes in Bivalent Gene Expression. Cancer Cell. 2019 01.35(1):140-155.e7. Pubmedid: 30595505. Pmcid: PMC6570409.
  • Stewart E, McEvoy J, Wang H, Chen X, Honnell V, Ocarz M, Gordon B, Dapper J, Blankenship K, Yang Y, Li Y, Shaw TI, Cho JH, Wang X, Xu B, Gupta P, Fan Y, Liu Y, Rusch M, Griffiths L, Jeon J, Freeman BB, Clay MR, Pappo A, Easton J, Shurtleff S, Shelat A, Zhou X, Boggs K, Mulder H, Yergeau D, Bahrami A, Mardis ER, Wilson RK, Zhang J, Peng J, Downing JR, Dyer MA. Identification of Therapeutic Targets in Rhabdomyosarcoma through Integrated Genomic, Epigenomic, and Proteomic Analyses. Cancer Cell. 2018 Sep.34(3):411-426.e19. Pubmedid: 30146332. Pmcid: PMC6158019.
  • Wang X, Jones DR, Shaw TI, Cho JH, Wang Y, Tan H, Xie B, Zhou S, Li Y, Peng J. Target-Decoy-Based False Discovery Rate Estimation for Large-Scale Metabolite Identification. J Proteome Res. 2018 Jul.17(7):2328-2334. Pubmedid: 29790753. Pmcid: PMC6252074.
  • Xie B, Wang Y, Jones DR, Dey KK, Wang X, Li Y, Cho JH, Shaw TI, Tan H, Peng J. Isotope Labeling-Assisted Evaluation of Hydrophilic and Hydrophobic Liquid Chromatograph-Mass Spectrometry for Metabolomics Profiling. Anal Chem. 2018 Jul.90(14):8538-8545. Pubmedid: 29883117. Pmcid: PMC6324930.
  • Tan H, Yang K, Li Y, Shaw TI, Wang Y, Blanco DB, Wang X, Cho JH, Wang H, Rankin S, Guy C, Peng J, Chi H. Integrative Proteomics and Phosphoproteomics Profiling Reveals Dynamic Signaling Networks and Bioenergetics Pathways Underlying T Cell Activation. Immunity. 2017 Mar.46(3):488-503. Pubmedid: 28285833. Pmcid: PMC5466820.
  • Lee KH, Zhang P, Kim HJ, Mitrea DM, Sarkar M, Freibaum BD, Cika J, Coughlin M, Messing J, Molliex A, Maxwell BA, Kim NC, Temirov J, Moore J, Kolaitis RM, Shaw TI, Bai B, Peng J, Kriwacki RW, Taylor JP. C9orf72 Dipeptide Repeats Impair the Assembly, Dynamics, and Function of Membrane-Less Organelles. Cell. 2016 Oct.167(3):774-788.e17. Pubmedid: 27768896. Pmcid: PMC5079111.
  • Joo JH, Wang B, Frankel E, Ge L, Xu L, Iyengar R, Li-Harms X, Wright C, Shaw TI, Lindsten T, Green DR, Peng J, Hendershot LM, Kilic F, Sze JY, Audhya A, Kundu M. The Noncanonical Role of ULK/ATG1 in ER-to-Golgi Trafficking Is Essential for Cellular Homeostasis. Mol Cell. 2016 May.62(4):491-506. Pubmedid: 27203176. Pmcid: PMC4993601.
  • Joo JH, Wang B, Frankel E, Ge L, Xu L, Iyengar R, Li-Harms X, Wright C, Shaw TI, Lindsten T, Green DR, Peng J, Hendershot LM, Kilic F, Sze JY, Audhya A, Kundu M. The Noncanonical Role of ULK/ATG1 in ER-to-Golgi Trafficking Is Essential for Cellular Homeostasis. Mol Cell. 2016 Jun.62(6):982. Pubmedid: 27315557.
  • Li Y, Wang X, Cho JH, Shaw TI, Wu Z, Bai B, Wang H, Zhou S, Beach TG, Wu G, Zhang J, Peng J. JUMPg: An Integrative Proteogenomics Pipeline Identifying Unannotated Proteins in Human Brain and Cancer Cells. J Proteome Res. 2016 Jul.15(7):2309-2320. Pubmedid: 27225868. Pmcid: PMC5033046.
  • Wong K, Shaw TI, Oladeinde A, Glenn TC, Oakley B, Molina M. Rapid Microbiome Changes in Freshly Deposited Cow Feces under Field Conditions. Front Microbiol. 2016 Apr.7:500. Pubmedid: 27148189. Pmcid: PMC4830129.
  • Shaw TI, Srivastava A, Chou WC, Liu L, Hawkinson A, Glenn TC, Adams R, Schountz T. Transcriptome sequencing and annotation for the Jamaican fruit bat (Artibeus jamaicensis). PLoS One. 2013 May.7(11):e48472. Pubmedid: 23166587. Pmcid: PMC3499531.
  • Bradnam KR, Fass JN, Alexandrov A, Baranay P, Bechner M, Birol I, Boisvert S, Chapman JA, Chapuis G, Chikhi R, Chitsaz H, Chou WC, Corbeil J, Del Fabbro C, Docking TR, Durbin R, Earl D, Emrich S, Fedotov P, Fonseca NA, Ganapathy G, Gibbs RA, Gnerre S, Godzaridis E, Goldstein S, Haimel M, Hall G, Haussler D, Hiatt JB, Ho IY, Howard J, Hunt M, Jackman SD, Jaffe DB, Jarvis ED, Jiang H, Kazakov S, Kersey PJ, Kitzman JO, Knight JR, Koren S, Lam TW, Lavenier D, Laviolette F, Li Y, Li Z, Liu B, Liu Y, Luo R, Maccallum I, Macmanes MD, Maillet N, Melnikov S, Naquin D, Ning Z, Otto TD, Paten B, Paulo OS, Phillippy AM, Pina-Martins F, Place M, Przybylski D, Qin X, Qu C, Ribeiro FJ, Richards S, Rokhsar DS, Ruby JG, Scalabrin S, Schatz MC, Schwartz DC, Sergushichev A, Sharpe T, Shaw TI, Shendure J, Shi Y, Simpson JT, Song H, Tsarev F, Vezzi F, Vicedomini R, Vieira BM, Wang J, Worley KC, Yin S, Yiu SM, Yuan J, Zhang G, Zhang H, Zhou S, Korf IF. Assemblathon 2: evaluating de novo methods of genome assembly in three vertebrate species. Gigascience. 2013 Jul.2(1):10. Pubmedid: 23870653. Pmcid: PMC3844414.
  • Shaw TI, Zhang M. HIV N-linked glycosylation site analyzer and its further usage in anchored alignment. Nucleic Acids Res. 2013 Jul.41(Web):W454-W458. Pubmedid: 23748959. Pmcid: PMC3692120.
  • Shaw TI, Ruan Z, Glenn TC, Liu L. STRAW: Species TRee Analysis Web server. Nucleic Acids Res. 2013 Jul.41(Web):W238-W241. Pubmedid: 23661681. Pmcid: PMC3692081.
  • Manzourolajdad A, Wang Y, Shaw TI, Malmberg RL. Information-theoretic uncertainty of SCFG-modeled folding space of the non-coding RNA. J Theor Biol. 2013 Feb.318:140-163. Pubmedid: 23160142. Pmcid: PMC3538908.
  • Schountz T, Shaw TI, Glenn TC, Feldmann H, Prescott J. Expression profiling of lymph node cells from deer mice infected with Andes virus. BMC Immunol. 2013 Apr.14:18. Pubmedid: 23570545. Pmcid: PMC3637227.
  • Srivastava A, Winker K, Shaw TI, Jones KL, Glenn TC. Transcriptome analysis of a North American songbird, Melospiza melodia. DNA Res. 2012 Nov.19(4):325-333. Pubmedid: 22645122. Pmcid: PMC3415294.
  • Wang Y, Manzour A, Shareghi P, Shaw TI, Li YW, Malmberg RL, Cai L. Stable stem enabled Shannon entropies distinguish non-coding RNAs from random backgrounds. BMC Bioinformatics. 2012 Apr.13 Suppl 5:S1. Pubmedid: 22537005. Pmcid: PMC3358654.
  • Shaw TI, Manzour A, Wang Y, Malmberg RL, Cai L. Analyzing modular RNA structure reveals low global structural entropy in microRNA sequence. J Bioinform Comput Biol. 2011 Apr.9(2):283-298. Pubmedid: 21523933.
  • Malmberg RL, Shaw TI, Cai L. RNApasta: a tool for analysis of RNA structural alignments. Int J Bioinform Res Appl. 2010 Dec.6(6):571-583. Pubmedid: 21354963.

Grants

Title: Integrated transcriptome-based prognostic and disease monitoring strategies in childhood AML
Sponsor: Amer Cancer Society
PI: Shaw, T.