BADR Lab

Overview

Gliomas are the most common primary tumors of the central nervous system and remain among the most aggressive and incurable human cancers. These tumors form a complex cellular ecosystem enriched in glioma stem cells (GSCs), a subpopulation with potent self-renewal capacity that drives tumor initiation, progression, and therapeutic resistance.

The BADR Lab investigates the genetic, molecular, and metabolic programs that sustain malignancy in GSCs. Our work focuses on the key regulatory hubs that control tumor plasticity, including transcriptional reprogramming and metabolic switching, which enable tumor cells to adapt to environmental stress and therapeutic pressure.

Using multidisciplinary approaches that integrate functional genomics, chemical biology, and proteomic and metabolomic profiling, we study GBM using patient-derived tumor models, brain organoid systems that recapitulate the human brain microenvironment, and in vivo tumor models. These platforms allow us to identify vulnerabilities within aggressive tumor populations.

Our studies have uncovered critical metabolic dependencies, including reliance on fatty acid metabolism, that support highly malignant GSC states and represent promising therapeutic targets. Building on these discoveries, we develop and test experimental therapeutic strategies designed to induce tumor-selective stress, disrupt metabolic adaptation, and overcome treatment resistance in glioblastoma.

Ultimately, our goal is to translate insights into tumor plasticity and metabolic adaptation into next-generation therapies for patients with glioblastoma.

Research Projects

Mission

The BADR Lab seeks to understand how brain tumor cells survive therapeutic stress and evolve into treatment-resistant disease. By integrating functional genomics, cancer biology, metabolism, and drug engineering, we aim to uncover new vulnerabilities in glioblastoma and translate these discoveries into innovative therapies.

Glioblastoma (GBM) remains one of the most aggressive human cancers. A defining feature of this disease is its remarkable cellular plasticity, metabolic adaptability, and resistance to therapy. Our laboratory investigates the biological mechanisms that enable tumor cells to persist and recur after treatment, and we develop strategies to target these survival pathways therapeutically.

Our research is organized around four interconnected areas

Tumor Plasticity and Glioma Stem Cells

• Glioblastoma tumors contain diverse cellular populations that dynamically transition between transcriptional states. This cellular plasticity enables tumor cells to evade therapy and repopulate tumors after treatment.
• Our laboratory studies the biology of glioma stem cells (GSCs) and the mechanisms that regulate transitions between tumor states. We develop reporters, dynamic cell-state models, and orthotopic tumor systems to track how aggressive tumor populations emerge.
• Using genetic targeting and functional genomics, we aim to identify the key regulators that control tumor cell fate. Understanding these mechanisms may allow us to prevent the emergence of therapy-resistant tumor states or reprogram them into less aggressive phenotypes.

Therapeutic Vulnerabilities in Brain Tumors

• Cancer cells rely on specific molecular pathways to survive the stresses of rapid growth and therapy. Identifying these tumor dependencies provides opportunities to develop targeted treatments.
• Our lab combines functional genetic screening, chemical biology, patient-derived tumor models, and brain organoid systems to uncover pathways that are essential for glioblastoma survival.
• Recent work from our group has identified critical roles for protein homeostasis pathways, stress signaling networks, and transcriptional regulators that sustain tumor growth.
• By defining these dependencies, we aim to develop precision therapeutic strategies that selectively target tumor cells while sparing normal brain tissue.

Metabolic Reprogramming

• Tumor cells rewire their metabolism to support proliferation, survive oxidative stress, and resist therapy. Our laboratory investigates how metabolic adaptation drives tumor progression in glioblastoma.
• We focus on pathways controlling lipid metabolism. Using metabolic profiling, genetic perturbation, and targeted inhibitors, we identify enzymes that are essential for tumor survival.
• Targeting these metabolic vulnerabilities can induce lipotoxic stress, impair DNA repair, and sensitize tumors to therapy, revealing promising opportunities for therapeutic intervention.

Engineering Next-Generation Therapies for Brain Tumors

• A major challenge in treating brain tumors is delivering therapeutic agents across the blood–brain barrier while minimizing systemic toxicity.

• Our laboratory develops innovative therapeutic platforms designed to improve drug delivery and treatment efficacy for brain tumors. These approaches include:

  • Exploring alternative delivery routes to the brain, including intranasal administration.
  • Targeted nanoparticle drug delivery systems.
  • Chimeric molecules (PROTACs) for targeted protein degradation.

• Novel strategies to enhance brain-specific drug penetration.

• By integrating drug discovery with advanced delivery technologies, we aim to develop next-generation therapeutics capable of overcoming resistance and improving outcomes for patients with glioblastoma.

Research Team

Christian E. Badr, PhD
Associate Professor of Neurology, Harvard Medical School and Massachusetts General Hospital
Director, BADR Lab

Hayk Mnatsakanyan, PhD
Postdoctoral Research Fellow in Department of Neurology, Harvard Medical School and Massachusetts General Hospital, BADR Lab

Cagri Cakici, PhD
Postdoctoral Research Fellow in Department of Neurology, Harvard Medical School and Massachusetts General Hospital, BADR Lab

Abigail G. Hewett, B.S
Research Technician, Department of Neurology, Massachusetts General Hospital, BADR Lab

Caroline M. Spangler-Sakata
Undergraduate Student, Department of Neurology, Massachusetts General Hospital, BADR Lab

Publications

View publications

Open Positions

We are continuously seeking highly motivated and talented individuals to join our research team. We welcome applicants at different levels of training/education (undergraduate, graduate and medical students, Residents and Fellows). Interested individuals should send a curriculum vitae to Dr. Christian E. Badr at badr.christian@mgh.harvard.edu.