Akdemir Lab

Deciphering central nervous system tumors for better diagnosis and treatment

We investigate how cancer genomes evolve, how oncogenic alterations reshape the tumor microenvironment, and how these changes influence disease progression and treatment response. By integrating spatial and single-cell genomics, 3D genome organization, and patient-derived tumors, we connect discoveries about genome structure to clinically relevant questions.

Departments of Neurosurgery and Genomic Medicine · Brain Tumor Center · The University of Texas MD Anderson Cancer Center, Houston

    Illustrative spot map of a glioma section, colored by niche. Select a niche to highlight it.

    Research

    Cancer genome evolution and spatial tissue organization are intertwined. We combine patient samples, advanced sequencing, imaging, and computational methods to understand how genomic alterations change tumor biology.

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    ecDNA, oncogene amplification and cancer evolution

    How does the architecture of oncogene amplification influence tumor evolution and response to therapy?

    We study extrachromosomal DNA (ecDNA), homogeneously staining regions, and other amplification structures in gliomas and brain metastases. By integrating DNA FISH, whole-genome sequencing, and spatial transcriptomics, we investigate how amplification architecture relates to tumor cell states, immune organization, and clinical outcomes.

    Key work: ERBB2 amplification in esophageal adenocarcinoma brain metastases

    • ecDNA
    • ERBB2 and EGFR
    • DNA FISH
    • Brain metastases
    • Therapy response
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    Spatial ecosystems of brain tumors

    Which oncogenic drivers reshape the cells around them, and where?

    We use spatial transcriptomics and single-cell profiling to study gliomas in their native tissue context. Integrating these maps with genomic alterations reveals how oncogenic drivers relate to malignant cell states, immune populations, vasculature, and spatial neighborhoods across primary and recurrent tumors.

    Key work: Oncogenic drivers shape the tumor microenvironment in human gliomas

    • Spatial transcriptomics
    • Single-cell RNA and ATAC
    • Tumor microenvironment
    • Glioma
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    Treatment-driven evolution and recurrence

    How do treatment and acquired mutations reshape recurrent gliomas?

    We study longitudinal tumor genomes, temozolomide-associated hypermutation, mismatch-repair alterations, and changes in malignant cell states after therapy. Our goal is to connect the evolutionary history of recurrent tumors with their changing spatial ecosystems and identify vulnerabilities that emerge during progression.

    • Longitudinal genomics
    • TMZ hypermutation
    • DNA repair
    • Glioma recurrence
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    Chordoma evolution and treatment resistance

    What keeps TBXT switched on in chordoma, and which tumors will come back after treatment?

    Chordoma is a rare tumor of the skull base and spine driven by the developmental transcription factor TBXT (brachyury). We are building a multi-omic atlas of chordomas from the skull base, mobile spine and sacrum, including tumors sampled at several points during treatment.

    By integrating single-cell, genomic and spatial profiling, we study how chordomas are regulated, how they evolve, and how they respond to therapy.

    • TBXT (brachyury)
    • scATAC-seq
    • Long-read WGS
    • Spatial transcriptomics
    • Radiation therapy
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    Chromatin architecture and mutation

    How does the folded genome decide where mutations land?

    Two meters of DNA fold into a nucleus a few micrometers wide, organized into self-interacting domains (TADs) that control gene regulation and DNA replication. We showed that somatic mutation rates track this 3D structure across cancers. We now use Hi-C and single-cell chromatin accessibility in brain tumors to connect genome folding with DNA damage, repair and tumor evolution.

    Key work: Nature Genetics 2020

    • Hi-C
    • scATAC-seq
    • Mutational processes
    • Epigenome
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    Complex rearrangements and tumor evolution

    What do shattered chromosomes do to gene regulation, and does it matter for patients?

    Catastrophic rearrangements rewire which genes sit next to which enhancers. We develop methods that use chromatin organization and long-read whole-genome sequencing to reconstruct rearranged chromosomes and predict the regulatory changes they cause, and we follow these changes from primary tumors to recurrence and brain metastasis.

    Key work: Nature Genetics 2020

    • Long-read WGS
    • Structural variants
    • Brain metastasis
    • Clinical genomics

    Tumors we study

    Our questions begin with patient tumors and are shaped by collaborations across neurosurgery, neuropathology, oncology, genomics, and computational biology.

    Glioblastoma and gliomas

    The most common malignant brain tumors in adults, and the focus of our spatial and single-cell work.

    Chordoma

    A rare tumor of the skull base and spine with few treatment options and little genomic data.

    Brain metastases

    We investigate how metastatic cancers, including esophageal adenocarcinoma and HER2-positive breast cancer, evolve and adapt within the brain.

    Other CNS tumors

    Rare and pediatric tumors where integrative multi-omics can sharpen diagnosis.

    Methods we work with

    Spatial transcriptomicsscRNA-seqscATAC-seqHi-CNanopore long-read WGSWhole-genome sequencingAlgorithm development DNA FISHecDNA analysis

    Software & data

    We develop computational approaches to interpret complex cancer genomes and spatially resolved tumors. Explore our publicly available tools and research outputs.

    Long-read genome analysis

    Workflows for interpreting structural variants, copy-number changes, and complex amplification from nanopore sequencing. Links to individual tools will be added as they are released.

    Research in progress

    Spatial genomics resources

    Associated preprints and publications describe the spatial and genomic datasets generated by the lab. Public data portals will be linked when releases are available.

    Explore selected publications →

    Selected publications

    The full and current list is on Google Scholar.

    1. Oncogenic drivers shape the tumor microenvironment in human gliomas

      bioRxiv 2025 · preprint

      Integrating spatial and genomic profiling to investigate how oncogenic drivers relate to the glioma microenvironment.

      Authors

      B Zhao*, CY Cho*, L Ye*, T Keal*, T Mitchell*, I Martin-Barrio*, C Abi Faraj, M Unal, J Alsing, NM Lawson, ER Kim, F Chavez, KM Rangel, SK Singh, JH McCarthy, DM Ashley, WKA Yung, V Puduvalli, G Nir, JS Weinberg, L Wang, KL Ligon, G Genovese, P Van Loo, PA Futreal, JT Huse†, JR Dixon†, FF Lang†, KC Akdemir†

    2. Recurrent ERBB2 alterations are associated with esophageal adenocarcinoma brain metastases

      Cancer Cell · accepted in principle; final publication details pending

      Identifying prevalent ERBB2 amplification in esophageal adenocarcinoma brain metastases and associations between amplification architecture and clinical outcomes.

      Authors

      N Lawson*, L Ye*, C Cho*, B Zhao*, T Mitchell, I Martin-Barrio, B Beernaert, M Banu, Y Lissanu, S Shaffer, H Tawbi, J Li, MK Gule-Monroe, JT Huse, MB Murphy, F Yin, FF Lang, EE Parker, JS Weinberg†, KC Akdemir†

    3. Somatic mutation distributions in cancer genomes vary with three-dimensional chromatin structure

      Nature Genetics 2020

      Linking regional somatic mutation patterns to the three-dimensional structure of the cancer genome.

      Authors

      KC Akdemir†, VT Le, JM Kim, S Killcoyne, DA King, Y Lin, Y Tian, A Inoue, SB Amin, FS Robinson, M Nimmakayalu, RE Herrera, EJ Lynn, K Chan, S Seth, LJ Klimczak, M Gerstung, DA Gordenin, J O'Brien, L Li, YL Deribe, RG Verhaak, PJ Campbell, R Fitzgerald, AJ Morrison, JR Dixon†, PA Futreal†

    4. Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer

      Nature Genetics 2020

      Investigating how structural rearrangements disrupt chromatin domains and regulatory organization.

      Authors

      KC Akdemir, VT Le, S Chandran, Y Li, RG Verhaak, R Beroukhim, PJ Campbell, L Chin, JR Dixon, PA Futreal, PCAWG Structural Variation Working Group and PCAWG Consortium

    * co-first authors, † co-corresponding authors

    News

    Recent milestones from the lab.

    NIH R35 MIRA award

    The lab received an NIH R35 MIRA award supporting our research program in cancer genome biology.

    ERBB2 brain metastasis study

    Our study of ERBB2 amplification architecture in esophageal adenocarcinoma brain metastases was accepted in principle at Cancer Cell; publication details will follow.

    Spatial glioma study

    We shared our work connecting oncogenic drivers to the tumor microenvironment in human gliomas. Read the preprint.

    Interested in joining?

    Learn about postdoctoral and student opportunities and reach out about current availability. Explore opportunities.

    People

    Computational biologists, data scientists and trainees from five countries, working closely with clinical and wet-lab collaborators.

    Kadir C. Akdemir

    Kadir C. Akdemir, PhD

    Principal investigator

    From Siirt, Turkey

    Hobbies spending time with his son and building Lego

    Alumni

      Join us

      We're looking for curious people who want to turn large, messy patient datasets into biological insight. We train lab members across computational and experimental approaches and support each person's next career step.

      Postdoctoral fellows

      Develop and apply algorithms for spatial transcriptomics, single-cell chromatin, Hi-C and long-read genome data from primary brain tumors. You'll work on tumor behavior, clinical outcomes and resistance to therapy, and build your own research program.

      Email Kadir with your CV, a short note on your background, how our interests intersect and your timeframe. Informal inquiries are welcome.

      See the job posting

      PhD and rotation students

      We are part of the MD Anderson UTHealth Houston Graduate School of Biomedical Sciences (GSBS). Apply to the graduate program rather than directly to the lab; first-year students rotate through about three labs before choosing a thesis lab.

      We usually host rotation students every quarter. Prospective students are welcome to get in touch with questions.

      Undergraduate and high school students

      We host students through the CPRIT-CURE Summer Undergraduate Program and the PCCSM program for STEM-focused high school and college students and first-year medical students.

      We especially welcome students from groups underrepresented in science and medicine. Contact Kadir about open positions.

      How we mentor

      • Every trainee owns a project with a clear question, and gets regular one-on-one time to shape it.
      • We write code that others can read and rerun, and we share methods and data openly.
      • Computational and clinical collaborators sit at the same table, so analyses stay close to patients.
      • We plan careers early, whether the next step is academia, industry or medicine.

      Funding and support

      Our research is made possible by federal, foundation and institutional support. We are grateful to our funders and to the patients and families who make this work possible.

      • NIH NIGMS R35 MIRA

        Maximizing Investigators' Research Award to Kadir C. Akdemir from the National Institute of General Medical Sciences

      • Andrew M. McDougall Brain Metastasis Clinic and Research Program

        MD Anderson Cancer Center

      • National Institute of General Medical Sciences (NIGMS)
      • National Cancer Institute
      • Break Through Cancer
      • MD Anderson Moon Shots Program
      • Chordoma Foundation
      • The Broach Foundation for Brain Cancer Research
      • Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation
      • Emerson Collective

      Contact

      Prospective lab members, collaborators and patients' advocates are welcome to reach out.

      Email
      kcakedemir@mdanderson.org
      Location
      Basic Science Research Building, 5th floor
      UT MD Anderson Brain Tumor Center
      Houston, Texas
      Social
      @kcakdemir
      Code
      github.com/akdemirlab

      Find us in Houston

      Basic Science Research Building
      The University of Texas MD Anderson Cancer Center
      Houston, Texas

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