Research

Across vertebrates and invertebrates, developmental signaling systems (e.g., Hedgehog, WNT, and BMP) govern the emergence of organized tissues and organs. These conserved pathways define tissue boundaries, and coordinate growth so that organs achieve reproducible size, pattern, and function. In both vertebrate embryos and Drosophila, specialized signaling centers secrete instructive cues that spread across fields of naïve cells to pattern developing structures with exquisite precision. These universal signaling networks form the blueprint of multicellular organization and are equally relevant to regeneration and disease, where their misregulation drives fibrosis, congenital malformations, and cancer.

Despite decades of study, key mysteries remain about how cells initiate, propagate, and spatially restrict developmental signals to achieve reproducible outcomes: We do not yet understand how cells acquire the molecular capacity (or “competency”) to launch or relay inductive cues, nor the roles of chromatin or metabolic states in encoding this central capability. The transcriptional and trafficking programs that define these competencies remain largely uncharted. Equally unclear is how spatial gating ensures that only specific recipient cells internalize vesicle-borne or receptor-bound signals, preserving tissue boundaries and communication fidelity.

These gaps obscure the molecular logic that enables developmental robustness, the ability of tissues to maintain pattern and proportion despite genetic or environmental noise.

The Chabu lab integrates Drosophila and vertebrate epithelial models to investigate a unifying framework in which cells across metazoans selectively acquire signal-initiation and relay competency states encoded by chromatin and trafficking programs.

Signal-initiation (secretion) competency is encoded by chromatin-regulated transcriptional programs that activate the machinery required for extracellular vesicle (EV) biogenesis and morphogen packaging. Relay competency equips recipient cells to decode and retransmit vesicle-borne cues through morphogen-activated receptor networks, amplifying and refining the signal as it propagates across the tissue. A spatial gating system ensures that signal uptake and downstream transcriptional responses occur only in correctly positioned cells.

Together, these processes form a conserved molecular circuit that allows developing tissues to encode, transmit, and decode positional information with extraordinary fidelity, ensuring predictable organ architecture.

Tumors evolve within complex signaling and metabolic ecosystems that shape their growth, therapeutic resistance, and immune evasion. Our lab investigates how the broader mutational landscape of cancers reconfigures these signaling architectures to promote malignant progression and limit treatment durability.

Oncogenic Networks and Tumor Ecosystems

We study how primary oncogenic drivers such as KRAS or EGFR cooperate with secondary mutations, including LKB1/STK11 and TP53, to sculpt tumor microenvironments (TMEs) that suppress immune activation and sustain therapy-resistant growth. Using integrated cell culture, clinical samples, and genetically engineered mouse models of pancreatic and lung cancers, we dissect how these cooperative mutations rewire trafficking, metabolism, and extracellular vesicle signaling to promote tumor immune escape.

Systemic Manifestations of Cancer Signaling

Beyond local invasion and metastasis, tumors can disrupt homeostasis across distant organs. We are elucidating the molecular mechanisms driving paraneoplastic syndromes (e.g., cachexia and nephropathies) that emerge independently of metastatic spread. Our goal is to uncover the vesicle and cytokine-based signaling axes through which tumors systemically remodel host physiology.

Therapeutic Reprogramming of the Tumor Microenvironment

To counteract these adaptive ecosystems, we are developing genetically programmable “smart” bacterial therapies that selectively colonize tumors and rewire their microenvironments toward immune activation. These live agents, engineered for glycan-guided tumor tropism, deliver RNA or protein payloads to silence immune-evasion genes and stimulate innate-to-adaptive immune cascades. Because they act through conserved stress and glycan-sensing pathways, these mutation-agnostic platforms have the potential to overcome heterogeneity-driven therapeutic resistance and achieve durable tumor control.