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Dwight Stambolian

University of Pennsylvania, PA·Genetics

The complement system is a set of blood and tissue proteins that act as a rapid-response arm of innate immunity, tagging microbes, dying cells and debris for clearance. It has to be kept tightly in check, because leftover activation causes inflammation that damages healthy tissue.

Fields

Genetics

Microbiology & Immunology

Medicine & Clinical Research

Topics

complement system

alternative pathway

complement factor H

Grants
1 known grant, through Oct 2028

What they work on

  1. Differentiate eight patient-derived iPSC lines into retinal pigment epithelium, four with CFH risk alleles and four gene-corrected isogenic controls, and quantify mRNA, protein and function of complement components, regulators and receptors.
  2. Measure intracellular alternative-pathway complement activity in risk-variant and corrected iPSC-RPE cells to test whether genetic variation shifts complement handling inside the cell as well as what is secreted.
  3. Compare the protein cargo of extracellular vesicles released from the apical versus basal surfaces of risk and control iPSC-RPE, testing whether CFH variants change vesicle content and amount.
  4. Characterize sub-cellular deposit formation by scanning electron microscopy and immunostaining, and test whether cigarette smoke extract and cytokines alter deposits and complement output in CFH risk lines.

More about the research

Aging, infection and inherited DNA variants can all tip that balance. This project asks how specific genetic variants change complement activity inside and around the cells at the back of the eye, the layer whose failure drives age-related macular degeneration (AMD), a leading cause of vision loss.

Why it matters

AMD is a major cause of blindness, and complement genes are among its strongest genetic risk factors, yet it is unclear what those variants actually do to cells. Linking CFH risk variants to measurable changes in complement output, vesicle cargo and sub-retinal deposits could reveal therapeutic targets aimed at the RPE itself. Because kidney and lung barrier cells are also hit by complement-driven disease, the findings may carry over to those organs.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Functional Analysis of Complement Variants in a Genotyped iPSC Epithelial Cell Model System

NIH · Dec 2023 – Oct 2028

Closest labs

Baerbel Rohrer

Medical University of South Carolina, SC·Medicine & Clinical Research

Characterize a perfused 3D RPE/choroid tissue chip built from stem cells, measuring gene expression by single-cell RNA sequencing, complement activation, Bruch's membrane formation and extracellular vesicles.

Jason Miller

University of Michigan, MI·Medicine & Clinical Research·Early-career

Determine the composition of lipid droplets, small fat-storage compartments, in human retinal pigment epithelium (RPE) cultures fed different lipid loads, using mass spectrometry.

Jianhai Du

West Virginia University, WV·Biochemistry

Trace how retinal pigment epithelium cells use the amino acid proline as fuel alongside glucose, using tracer methods and mass spectrometry.

The school

University of Pennsylvania: 90 labs on PI Pages, $2.2B a year on research, 750 research doctorates a year.

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