Research

Investigating fundamental mechanisms of immune surveillance during cancer development and therapy

Research Overview

Ma Lab investigates the fundamental mechanisms of immune surveillance during cancer development and therapy. We focus on understanding how DNA damage responses, mutagenesis processes, and epigenetic disruptions shape tumor immunogenicity and influence treatment resistance, with the ultimate goal of developing novel cancer vaccines, TCR therapies, and combination treatments that maximize the potential of the immune system.

Research Directions

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DNA Damage Repair & Tumor Immunology

Our previous research demonstrated that DNA damage repair deficiencies lead to accumulation of immunogenic mutations, fundamentally alter the tumor immune microenvironment, and enhance tumor sensitivity to immune checkpoint blockade therapy. However, the complex interplay between DNA damage response pathways and immune surveillance mechanisms in cancer requires deeper investigation to fully understand and therapeutically exploit.

Research Aims:

  • Understanding how DNA damage repair deficient tumors developed primary and acquired resistance to immune checkpoint blockade therapies
  • Characterizing DNA damage response in tumor-infiltrating immune cells and its impact on anti-tumor immunity
  • Exploring how biochemical features of neoantigen peptides determine the immunogenicity of the mutagenesis processes
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Immunological Vulnerability of Epigenetic Dysregulated Tumors

Epigenetic dysregulation is a hallmark of cancer progression and drug resistance development. This dysregulation can also drive aberrant expression of non-canonical tumor antigens, potentially creating immunological vulnerabilities that may be targeted for therapeutic benefit.

Research Aims:

  • Elucidating the landscape of non-canonical tumor antigens associated with diverse epigenetic dysregulation in tumors
  • Developing cancer vaccine and TCR therapies to target epigenetic dysregulation
  • Identifying biomarkers for personalized immunotherapy approaches

Research Approaches

Our research employs diverse experimental approaches including cellular and animal models, patient samples and clinical cohorts, synthetic biology tools, and computational immunogenomic analyses to investigate these fundamental questions.

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Experimental Models

Cellular and animal models to study immune-tumor interactions and therapeutic responses

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Clinical Cohorts

Patient samples and clinical data to validate findings and identify biomarkers

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Synthetic Biology

Engineering tools for neoantigen discovery and TCR therapy development

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Computational Analysis

Immunogenomic analyses of large-scale genomic and immunologic datasets

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Translational Research

Bridging basic discoveries to clinical applications and therapeutic development

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Collaborative Science

Interdisciplinary partnerships with clinicians, computational biologists, and industry

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