Where microscopic signals shape human destiny.
At the heart of almost every human cell, a primary cilium runs the show—sensing, deciding, directing. When this tiny organelle falters, whole organs drift off-script: kidneys fill with cysts, eyes lose sight, brains miswire. My work follows that thread—how a single cellular command center safeguards systems as different as retina and kidney, and what we can do when it goes wrong.
From there, I trace how this organelle is built, fed, and heard: how lipids sculpt its membrane identity, how intraflagellar transport ferries cargo in precisely timed convoys, and how ion channels and GPCRs turn mechanical or chemical cues into transcriptional decisions.
Ph.D. Work — Photoreceptors
When a Sensory Organelle Loses Its Supply Line
What are photoreceptors?
They're the light-sensing neurons in your retina. Each one has a "outer segment" packed with stacks of membrane discs that catch photons. That outer segment is actually a modified primary cilium—a compartment that can't make its own proteins and must be constantly resupplied from the cell body.
The core problem
If the cilium's import/transport system falters, essential proteins (like rhodopsin, your primary light receptor) don't reach the outer segment. Structure collapses, and vision fades.
What I asked
- How do specific lipids and trafficking machines keep this ciliary supply line running?
- Which parts of the transport system are needed to build the cilium versus maintain it day-to-day?
What I did
INPP5E & lipids:
Using conditional mouse knockouts, I showed that the phosphoinositide phosphatase INPP5E shapes the lipid environment at the ciliary base, organizing actin and ensuring proteins load correctly for the trip into the outer segment.
IFT-A components (IFT43, IFTAP):
I dissected how these lesser-known parts of the intraflagellar transport "fleet" govern cargo movement and long-term stability of the cilium.
Why it matters
Linking a single enzyme or transport subunit to a specific failure mode—mislocalized actin, blocked protein delivery—explains why mutations in these genes cause blindness (e.g., Joubert syndrome, MORM, retinitis pigmentosa). It also gives us defined targets to rescue before degeneration begins.
Postdoctoral Work — Kidneys & Cysts
When the Cilium's Message Doesn't Get Through
Context
Your kidney tubule cells also carry a primary cilium—this time to monitor fluid flow and chemical cues, helping the tissue keep its architecture. In Autosomal Dominant Polycystic Kidney Disease (ADPKD), mutations in PKD1/PKD2 (polycystins) derail that ciliary signaling. Over decades, fluid-filled cysts replace healthy tissue.
The core problem
We know the polycystin complex lives in the cilium and is critical, but what exact signal is lost, and is restoring that signal enough to stop cysts?
What I'm asking now
- Which cilium-originated signals keep kidney epithelial cells "in line"?
- Can we reintroduce those signals—selectively in the cilium—and reset the disease trajectory?
What I do
Precision control of inputs:
I use engineered versions of the polycystin channel and a chemogenetic toolset to open the "gate" only inside the cilium, on demand.
Read the consequences:
With imaging, transcriptomics, and epigenomics, I watch how cells respond—what genes flip, what pathways restore order.
Test causality:
If flipping that one switch halts cyst growth in models, it's a powerful proof that targeting ciliary signaling directly can be therapeutic.
Why it matters
ADPKD affects millions and has no cure. By defining the minimal signals needed to keep tubules cyst-free, we lay the groundwork for small-molecule "correctors" or gene-based strategies that restore ciliary communication rather than just managing symptoms.
⚡ Ciliary Calcium Dynamics
When a Single Ion Speaks Volumes
While the cilium hosts many messengers, calcium (Ca²⁺) is its loudest voice. Unlike the rest of the cell, the cilium is a compartment with its own rules — a nanodomain where calcium spikes are rare, confined, and deeply influential. These signals don't just flick switches. They reprogram cells.
In the Delling Lab, I focus on how ciliary calcium influx, particularly through the polycystin channel complex (PC1/PC2), regulates transcriptional networks that maintain tissue architecture.
What I Do:
- Use chemogenetic tools to control calcium entry exclusively inside the cilium, with second-by-second precision.
- Combine this with live imaging, transcriptomics, and epigenomic profiling to map what this ionic whisper changes — from chromatin marks to gene expression.
Why It Matters:
This work redefines calcium not just as a fast signaling ion but as a transcriptional regulator within the cilium. By showing that restoring only ciliary calcium is enough to rescue disease features in ADPKD models, we highlight it as a minimal therapeutic input — a master lever to reboot order.