Dr. Mitchell Knutson

Seminar Details

Host: Dr. Vishal Gohil/ Dr. Paul Lindahl

Time: 4:00pm-5:00pm

Location: BICH Rm. 108

Seminar Abstract

Iron is indispensable for oxygen transport, mitochondrial respiration, and DNA synthesis, yet excess iron is cytotoxic because it catalyzes the generation of reactive oxygen species. Pathological iron overload occurs in hereditary hemochromatosis and in transfusion-dependent β-thalassemia, where progressive deposition in the liver, heart, pancreas, and endocrine tissues drives organ dysfunction and failure. Although systemic regulation of iron balance is well understood, the membrane transporters that mediate cellular iron uptake during overload remain incompletely defined. The identification of these routes is opening new opportunities for tissue-selective therapy. Current research centers on ZIP14 (SLC39A14), a broad-specificity metal-ion transporter that can mediate the cellular uptake of Zn²⁺, Fe²⁺, and Mn²⁺. Using whole-body and tissue-specific Zip14 knockout mice, we have delineated organs and cell types that depend on ZIP14 for iron acquisition under overload conditions and have been testing whether suppressing this pathway can limit iron deposition and iron-driven cell death (ferroptosis). These genetic models reveal both the contribution of ZIP14 to disease-associated iron loading and the consequences of its loss for zinc and manganese homeostasis, thereby defining the selectivity and safety constraints of any therapeutic strategy. The seminar will summarize these findings and discuss how transporter-level targeting might complement existing iron chelation–based approaches in iron overload disorders.