Mingnan Chen
University of Utah, UT·Pharmacology
Autoimmune disease happens when the immune system turns on the body's own tissues, as in type 1 diabetes (T1D) and multiple sclerosis. Most available drugs dampen immunity broadly, hitting both the activated cells doing the damage and the naive cells that have never been triggered.
- Fields
Pharmacology
Microbiology & Immunology
Biomedical Engineering
- Topics
programmed death-1
autoimmune disease
type 1 diabetes
- Grants
- 4 known grants, through Jan 2031
What they work on
- Determine why a depleting anti-PD-1 antibody delays diabetes in early insulitis but accelerates it in late insulitis in NOD mice, profiling pancreatic islets and systemic immune cells by single-cell RNA sequencing and flow cytometry before and after treatment.
- Define why a depleting antibody and a PD-1 immunotoxin produce opposite outcomes, by comparing immune cell dynamics and gene expression after each, and testing whether removing the cells that drive the pro-autoimmune response prevents it.
- Test whether Fc-free PD-1 depleting agents, an albumin-amended antibody-drug conjugate (A3DC) and a bispecific killer cell engager (BiKE), protect late-insulitis NOD mice from high blood sugar without triggering harmful immune activation.
- Characterize and compare mouse PD-1 BiKEs, antibody-based molecules that bridge natural killer cells to target cells via the CD16 receptor, and establish their efficacy and safety in mouse models of autoimmune disease.
- Generate a library of 24 PD-1 A3DCs, in which albumin replaces the antibody Fc region, and select candidates based on neonatal Fc receptor binding and toxicity to PD-1+ cells for testing in a mouse type 1 diabetes model.
- Characterize PD-1 CAR Tregs, regulatory T cells engineered to target PD-1 on activated effector T cells, measuring binding specificity, regulatory phenotype, cytokine secretion and suppression, against a reference CAR Treg directed at the myelin antigen MOG.
- Evaluate whether PD-1 CAR Tregs restore immune tolerance in two experimental autoimmune encephalomyelitis (EAE) mouse models, using clinical disease scores and suppression of demyelinating effector T cells while checking that anti-infection immunity is preserved.
More about the research
The result can be prolonged low lymphocyte counts, general immune suppression and greater vulnerability to infection and cancer. A unifying idea runs through this lab's four projects: aim treatment at cells carrying PD-1 (programmed death-1), a surface marker found mainly on activated effector lymphocytes, while sparing PD-1-negative naive cells so the immune repertoire recovers once the drug clears. Earlier work using an immunotoxin — a cell-killing toxin attached to a targeting protein — confirmed those advantages but is not well suited to long-term treatment, so the lab is engineering alternative formats and asking how each one interacts with the diseased immune system.
Why it matters
People with type 1 diabetes, multiple sclerosis and other autoimmune conditions, and transplant recipients, currently face therapies that either fail to stop disease or suppress immunity broadly enough to raise infection and cancer risk. Agents that remove only PD-1-positive effector cells, and CAR Tregs aimed at those cells, could offer more selective immune suppression. Mapping how disease stage changes the response may also help match such treatments to the right patients at the right time.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Deciphering the Interplay of Depleting Anti-PD-1 Antibodies and Autoimmune Environments in Type-1 Diabetes: Towards Better Utility of Therapeutic Antibody
NIH · Feb 2026 – Jan 2031
Albumin-Amended Antibody Drug Conjugate (A3DC) for Immunosuppression
NIH · Apr 2025 – Nov 2027
PD-1 BiKE: Targeting and Depleting PD-1 Positive Cells for Autoimmune Disease Treatment
NIH · Jul 2025 – Jun 2027
Closest labs
Booki Min
Northwestern University, IL·Microbiology & Immunology
Determine how Lag3, an inhibitory surface co-receptor, lets Foxp3+ regulatory T cells suppress autoimmune neuroinflammation, using mice with the Lag3 outer domain, cytoplasmic tail or KIEELE motif deleted only in Tregs.
Igal Ifergan
University of Cincinnati, OH·Microbiology & Immunology
Characterize mature (CD27- CD11b+) and immature (CD27+ CD11b-) natural killer cell subsets in the brain and spinal cord across stages of relapsing-remitting EAE, a mouse model of MS, using single-cell RNA sequencing.
Jeffrey Miller
University of Minnesota, MN·Microbiology & Immunology
Engineer iPSC-derived NK (iNK) cells with gene edits that improve homing and migration into tumors, tolerance of low oxygen (hypoxia), and survival after transfer into patients with solid tumors.
The school
University of Utah: 58 labs on PI Pages, $789M a year on research, 366 research doctorates a year.
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