Darryl Shibata, MD

After attending UCLA for his undergraduate degree, Dr. Shibata obtained his medical degree from the Keck School of Medicine of USC. After completing his internship training in pediatrics from UC San Diego, Dr. Shibata returned to USC for his residency and fellowship at LAC+USC Medical Center. Currently, Dr. Shibata has clinical appointments at both LAC+USC Medical Center and USC/Norris Comprehensive Cancer Center. In addition to his wide array of responsibilities in the research, education and practitioner capacities, Dr. Shibata sits on the editorial board of the BMC Cancer Journal and the American Journal of Pathology.

• Photolithographic Tumor DNA Isolation
  NIH · R21CA267245 · Jul 22, 2022 – May 31, 2025 · Role: Principal Investigator
• Arizona Cancer and Evolution Center (ACE)
  NIH · U54CA217376 · Apr 12, 2018 – Mar 31, 2024 · Role: Co-Principal Investigator
• Born to be Bad: Is Abnormal Cell Mobility Already Present At Initiation?
  NIH · R21CA185016 · Jul 30, 2014 – May 31, 2018 · Role: Principal Investigator
• How Do NSAIDs Prevent Colorectal Cancer
  NIH · R21CA170814 · Sep 13, 2012 – Aug 31, 2015 · Role: Principal Investigator
• Tumor Diversity As A Biomarker For Colorectal Cancer
  NIH · R21CA149990 · Apr 1, 2010 – Mar 31, 2014 · Role: Principal Investigator
• How Do Colorectal Cancers Arise Despite Surveillance?
  NIH · R33CA111940 · Aug 1, 2005 – Jun 30, 2010 · Role: Principal Investigator
• HUMAN COLON STEM CELL AND CRYPT DYNAMICS
  NIH · R21DK061140 · Sep 30, 2001 – Aug 31, 2005 · Role: Principal Investigator
• Fixing Fixed DNA
  NIH · R21CA091301 · Jul 1, 2001 – Jun 30, 2004 · Role: Principal Investigator
• Mouse Models of Early Intestinal Neoplasia
  NIH · R01CA080077 · Jan 1, 1999 – Mar 31, 2010 · Role: Principal Investigator
• PATHOLOGY OF TUMOR GROWTH
  NIH · R01CA070858 · May 21, 1997 – Apr 30, 2001 · Role: Principal Investigator
• PATHOLOGY OF TUMOR GROWTH
  NIH · R55CA070858 · Sep 15, 1996 – Apr 30, 1997 · Role: Principal Investigator
• PATHOLOGY OF GASTRIC CANCER
  NIH · R01CA058704 · Feb 1, 1993 – Jan 31, 1999 · Role: Principal Investigator

• Differences between mitotically old and young endometrial tumors. J Pathol. 2026 Jul 08.. View in PubMed
• Fluctuating DNA methylation sites encode colorectal tumour growth history. bioRxiv. 2026 Jul 02.. View in PubMed
• Annotation-Based Gene-Peak Links Improve Regulatory Network Prediction of Gene Expression in Human Kidney Multi-Omics. bioRxiv. 2026 Jun 17.. View in PubMed
• Conception-calibrated male pediatric tumor mitotic clocks. Commun Biol. 2026 Jun 09.. View in PubMed
• PHYFUM: Phylogenetic Reconstruction of Normal and Pre-malignant Tissue Evolution Using Fluctuating Methylation. bioRxiv. 2026 May 07.. View in PubMed
• Aggressive Neuroblastomas Start Growing after Infancy. bioRxiv. 2026 Mar 13.. View in PubMed
• Negative Selection Maintains Grossly Altered but Broadly Stable Karyotypes in Metastatic Colorectal Cancer. Cancer Discov. 2026 Feb 06; 16(2):218-234.. View in PubMed
• Spatially Discontinuous Mutation Topographies in Ductal Carcinoma In Situ Reveal Noncompetitive Growth Dynamics. Cancer Res. 2025 Dec 15; 85(24):5084-5097.. View in PubMed
• Epigenetic conservation infers that colorectal cancer progenitors retain the phenotypic plasticity of normal colon. Sci Rep. 2025 Nov 20; 15(1):40941.. View in PubMed
• Mapping the temporal landscape of breast cancer using epigenetic entropy. Commun Biol. 2025 Oct 16; 8(1):1477.. View in PubMed
• Fluctuating DNA methylation tracks cancer evolution at clinical scale. Nature. 2025 09; 645(8081):764-773.. View in PubMed
• Human brain ancestral barcodes. Elife. 2025 Jun 10; 13.. View in PubMed
• Developmental hematopoietic stem cell variation explains clonal hematopoiesis later in life. Nat Commun. 2024 11 26; 15(1):10268.. View in PubMed
• Human Brain Ancestral Barcodes. bioRxiv. 2024 Nov 12.. View in PubMed
• Mapping the Temporal Landscape of Breast Cancer Using Epigenetic Entropy. Res Sq. 2024 Oct 28.. View in PubMed
• Developmental hematopoietic stem cell variation explains clonal hematopoiesis later in life. bioRxiv. 2024 Mar 05.. View in PubMed
• Editorial Expression of Concern: Adenomatous polyposis coli (APC) regulates miR17-92 cluster through β-catenin pathway in colorectal cancer. Oncogene. 2024 Mar; 43(11):837.. View in PubMed
• Testing Adaptive Therapy Protocols Using Gemcitabine and Capecitabine in a Preclinical Model of Endocrine-Resistant Breast Cancer. Cancers (Basel). 2024 Jan 06; 16(2).. View in PubMed
• Growth Dynamics of Ductal Carcinoma in Situ Recapitulate Normal Breast Development. bioRxiv. 2023 Oct 02.. View in PubMed
• Testing Adaptive Therapy Protocols using Gemcitabine and Capecitabine on a Mouse Model of Endocrine-Resistant Breast Cancer. bioRxiv. 2023 Sep 22.. View in PubMed
• The co-evolution of the genome and epigenome in colorectal cancer. Nature. 2022 11; 611(7937):733-743.. View in PubMed
• Phenotypic plasticity and genetic control in colorectal cancer evolution. Nature. 2022 11; 611(7937):744-753.. View in PubMed
• Homeostasis limits keratinocyte evolution. Proc Natl Acad Sci U S A. 2022 08 30; 119(35):e2006487119.. View in PubMed
• Lineage tracing in human tissues. J Pathol. 2022 07; 257(4):501-512.. View in PubMed
• Gattaca: Base-Pair Resolution Mutation Tracking for Somatic Evolution Studies using Agent-based Models. Mol Biol Evol. 2022 04 11; 39(4).. View in PubMed
• Fluctuating methylation clocks for cell lineage tracing at high temporal resolution in human tissues. Nat Biotechnol. 2022 05; 40(5):720-730.. View in PubMed
• A Bayesian hierarchical model to estimate DNA methylation conservation in colorectal tumors. Bioinformatics. 2021 12 22; 38(1):22-29.. View in PubMed
• Functional human genes typically exhibit epigenetic conservation. PLoS One. 2021; 16(9):e0253250.. View in PubMed
• Navigating the path to distant metastasis. Nat Genet. 2020 07; 52(7):642-643.. View in PubMed
• Visualizing Human Colorectal Cancer Intratumor Heterogeneity with Phylogeography. iScience. 2020 Jul 24; 23(7):101304.. View in PubMed
• Deep learned tissue “fingerprints” classify breast cancers by ER/PR/Her2 status from H&E images. Sci Rep. 2020 04 29; 10(1):7275.. View in PubMed
• Minimal barriers to invasion during human colorectal tumor growth. Nat Commun. 2020 03 09; 11(1):1280.. View in PubMed
• Epigenetic Conservation Is a Beacon of Function: An Analysis Using Methcon5 Software for Studying Gene Methylation. JCO Clin Cancer Inform. 2020 02; 4:100-107.. View in PubMed
• Mutational signatures in colon cancer. BMC Res Notes. 2019 Dec 03; 12(1):788.. View in PubMed
• HiLDA: a statistical approach to investigate differences in mutational signatures. PeerJ. 2019; 7:e7557.. View in PubMed
• Cancer cell evolution through the ages. Science. 2019 08 02; 365(6452):440-441.. View in PubMed
• Tumorigenesis as the Paradigm of Quasi-neutral Molecular Evolution. Mol Biol Evol. 2019 07 01; 36(7):1430-1441.. View in PubMed
• Somatic cell evolution: how to improve with age. J Pathol. 2019 Jan; 247(1):3-5.. View in PubMed
• Epigenetic Heterogeneity in Human Colorectal Tumors Reveals Preferential Conservation And Evidence of Immune Surveillance. Sci Rep. 2018 11 23; 8(1):17292.. View in PubMed
• Evolutionary Stem Cell Poker and Cancer Risks: The Paradox of The Large And Small Intestines. Curr Pathobiol Rep. 2018 Sep; 6(3):193-198.. View in PubMed
• Spatial mutation patterns as markers of early colorectal tumor cell mobility. Proc Natl Acad Sci U S A. 2018 05 29; 115(22):5774-5779.. View in PubMed
• Classifying the evolutionary and ecological features of neoplasms. Nat Rev Cancer. 2017 10; 17(10):605-619.. View in PubMed
• Between-region genetic divergence reflects the mode and tempo of tumor evolution. Nat Genet. 2017 Jul; 49(7):1015-1024.. View in PubMed
• Early mutation bursts in colorectal tumors. PLoS One. 2017; 12(3):e0172516.. View in PubMed
• Management and outcomes following pancreaticoduodenectomy for ampullary adenocarcinoma. Am J Surg. 2017 Nov; 214(5):856-861.. View in PubMed
• Single cell lineage tracing reveals a role for TgfβR2 in intestinal stem cell dynamics and differentiation. Proc Natl Acad Sci U S A. 2016 10 25; 113(43):12192-12197.. View in PubMed
• At least two well-spaced samples are needed to genotype a solid tumor. BMC Cancer. 2016 Mar 25; 16:250.. View in PubMed
• Synchronous rectal adenocarcinoma and splenic marginal zone lymphoma. Curr Oncol. 2016 Feb; 23(1):e70-4.. View in PubMed
• HistoMosaic Detecting KRAS G12V Mutation Across Colorectal Cancer Tissue Slices through in Situ PCR. Anal Chem. 2016 Mar 01; 88(5):2792-8.. View in PubMed
• Ethnic differences in cross-sectional associations between impaired glucose regulation, identified by oral glucose tolerance test or HbA1c values, and cardiovascular disease in a cohort of European and South Asian origin. Diabet Med. 2016 Mar; 33(3):340-7.. View in PubMed
• Derivation of induced pluripotent stem cells from orangutan skin fibroblasts. BMC Res Notes. 2015 Oct 16; 8:577.. View in PubMed
• Induced pluripotent stem cell models of Zellweger spectrum disorder show impaired peroxisome assembly and cell type-specific lipid abnormalities. Stem Cell Res Ther. 2015 Aug 29; 6:158.. View in PubMed
• Many private mutations originate from the first few divisions of a human colorectal adenoma. J Pathol. 2015 Nov; 237(3):355-62.. View in PubMed
• Can oncology recapitulate paleontology? Lessons from species extinctions. Nat Rev Clin Oncol. 2015 May; 12(5):273-85.. View in PubMed
• A Big Bang model of human colorectal tumor growth. Nat Genet. 2015 Mar; 47(3):209-16.. View in PubMed
• Diffuse large B-cell lymphoma of germinal center and nongerminal center phenotypes presenting concurrently at the same anatomic site: intratumoral heterogeneity or composite lymphoma? Appl Immunohisto . View in PubMed
• Ancestral inference in tumors: how much can we know? J Theor Biol. 2014 Oct 21; 359:136-45. Zhao J, Siegmund KD , Shibata D , Marjoram P . . View in PubMed
• Deep sequencing reveals lack of a clonal relationship between a metachronous classical hodgkin and diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2014 Jun; 14(3):e87-93.. View in PubMed
• Direct measurements of human colon crypt stem cell niche genetic fidelity: the role of chance in non-darwinian mutation selection. Front Oncol. 2013 Oct 14; 3:264.. View in PubMed
• Occult progression by Apc-deficient intestinal crypts as a target for chemoprevention. Carcinogenesis. 2014 Jan; 35(1):237-46.. View in PubMed
• miR-675 mediates downregulation of Twist1 and Rb in AFP-secreting hepatocellular carcinoma. Ann Surg Oncol. 2013 Dec; 20.. View in PubMed
• Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer. Science. 2013 Feb 01; 339(6119):543-8.. View in PubMed
• Single-molecule genomic data delineate patient-specific tumor profiles and cancer stem cell organization. Cancer Res. 2013 Jan 01; 73(1):41-9.. View in PubMed
• The gene expression profiles of induced pluripotent stem cells from individuals with childhood cerebral adrenoleukodystrophy are consistent with proposed mechanisms of pathogenesis. Stem Cell Res Ther. 2012 Oct 04; 3(5):39.. View in PubMed
• Cancer. Heterogeneity and tumor history. Science. 2012 Apr 20; 336(6079):304-5.. View in PubMed
• Heterogeneity and randomness of DNA methylation patterns in human embryonic stem cells. DNA Cell Biol. 2012 Jun; 31(6):893-907.. View in PubMed
• The role of theorem proving in systems biology. J Theor Biol. 2012 May 07; 300:57-61.. View in PubMed
• Epigenetic subgroups of esophageal and gastric adenocarcinoma with differential GATA5 DNA methylation associated with clinical and lifestyle factors. PLoS One. 2011; 6(10):e25985.. View in PubMed
• Different phenotypic consequences of simultaneous versus stepwise Apc loss. Oncogene. 2012 Apr 19; 31(16):2028-38.. View in PubMed
• Molecular tumor clocks to study the evolution of drug resistance. Mol Pharm. 2011 Dec 05; 8(6):2050-4.. View in PubMed
• High DNA methylation pattern intratumoral diversity implies weak selection in many human colorectal cancers. PLoS One. 2011; 6(6):e21657.. View in PubMed
• Reduction of pancreatic acinar cell tumor multiplicity in Dnmt1 hypomorphic mice. Carcinogenesis. 2011 Jun; 32(6):829-35.. View in PubMed
• A stem cell niche dominance theorem. BMC Syst Biol. 2011 Jan 08; 5:4.. View in PubMed
• Mutation and epigenetic molecular clocks in cancer. Carcinogenesis. 2011 Feb; 32(2):123-8.. View in PubMed
• A stem cell niche dominance theorem. J Stem Cells Regen Med. 2010; 6(2):98.. View in PubMed
• Using DNA methylation patterns to infer tumor ancestry. PLoS One. 2010 Aug 09; 5(8):e12002.. View in PubMed
• Is there any genetic instability in human cancer? DNA Repair (Amst). 2010 Aug 05; 9(8):858; discussion 859-60. Shibata D , Lieber MR . . View in PubMed
• Identification and functional relevance of de novo DNA methylation in cancerous B-cell populations. J Cell Biochem. 2010 Mar 01; 109(4):818-27.. View in PubMed
• Hormone therapy, DNA methylation and colon cancer. Carcinogenesis. 2010 Jun; 31(6):1060-7.. View in PubMed
• A simple algebraic cancer equation: calculating how cancers may arise with normal mutation rates. BMC Cancer. 2010 Jan 05; 10:3.. View in PubMed
• Systems biologists seek fuller integration of systems biology approaches in new cancer research programs. Cancer Res. 2010 Jan 01; 70(1):12-3.. View in PubMed
• Many colorectal cancers are “flat” clonal expansions. Cell Cycle. 2009 Jul 15; 8(14):2187-93.. View in PubMed
• Inferring clonal expansion and cancer stem cell dynamics from DNA methylation patterns in colorectal cancers. Proc Natl Acad Sci U S A. 2009 Mar 24; 106(12):4828-33.. View in PubMed
• Older individuals appear to acquire mitotically older colorectal cancers. J Pathol. 2009 Mar; 217(4):483-8.. View in PubMed
• Urinary tract infections and reduced risk of bladder cancer in Los Angeles. Br J Cancer. 2009 Mar 10; 100(5):834-9.. View in PubMed
• Inferring human stem cell behaviour from epigenetic drift. J Pathol. 2009 Jan; 217(2):199-205.. View in PubMed
• Water intake and bladder cancer risk in Los Angeles County. Int J Cancer. 2008 Oct 01; 123(7):1649-56.. View in PubMed
• Modeling DNA methylation in a population of cancer cells. Stat Appl Genet Mol Biol. 2008; 7(1):Article.. View in PubMed
• Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice. J Transl Med. 2008 May 19; 6:26.. View in PubMed
• Inferring relative numbers of human leucocyte genome replications. Br J Haematol. 2008 Jun; 141(6):862-71.. View in PubMed
• Unregulated smooth-muscle myosin in human intestinal neoplasia. Proc Natl Acad Sci U S A. 2008 Apr 08; 105(14):5513-8.. View in PubMed
• Tractable Cre-lox system for stochastic alteration of genes in mice. Nat Methods. 2008 Mar; 5(3):227-9.. View in PubMed
• Mistakes make history: visualizing intestinal tectonics. Gastroenterology. 2008 Feb; 134(2):628-31.. View in PubMed
• Stem cells as common ancestors in a colorectal cancer ancestral tree. Curr Opin Gastroenterol. 2008 Jan; 24(1):59-63.. View in PubMed
• Ancestral trees for modeling stem cell lineages genetically rather than functionally: understanding mutation accumulation and distinguishing the restrictive cancer stem cell propagation theory and the unrestricted cell propagation theory of human tumorigenesis. Breast Dis. 2008; 29:15-25.. View in PubMed
• The fuzzy math of solid tumor stem cells: a perspective. Cancer Res. 2007 Oct 01; 67(19):8985-8.. View in PubMed
• Lack of increases in methylation at three CpG-rich genomic loci in non-mitotic adult tissues during aging. BMC Med Genet. 2007 Jul 31; 8:50.. View in PubMed
• IL-12 facilitates both the recovery of endogenous hematopoiesis and the engraftment of stem cells after ionizing radiation. Exp Hematol. 2007 Feb; 35(2):203-13.. View in PubMed
• The stem cell population of the human colon crypt: analysis via methylation patterns. PLoS Comput Biol. 2007 Mar 02; 3(3):e28.. View in PubMed
• Stem cell chronicles: autobiographies within genomes. Stem Cell Rev. 2007 Jan; 3(1):94-103.. View in PubMed

• Lenz, Heinz-Josef
• Siegmund, Kimberly
• Wiemels, Joseph
• Peters, Anne
• Liang, Gangning
• Haiman, Christopher