About

Dr. Iqbal Hamza is a professor in the Department of Animal & Avian Sciences at the University of Maryland. His research focuses on uncovering heme trafficking pathways in eukaryotes, with pioneering work utilizing the invertebrate model C. elegans. His studies have demonstrated that this roundworm does not synthesize heme but instead utilizes environmental heme to produce heme-containing proteins, challenging the existing paradigm of heme synthesis in free-living eukaryotes. His work identified the first eukaryotic heme importer/transporter (HRG-1), which is conserved across species including zebrafish and humans, and elucidated mechanisms of heme export and inter-organ communication involving HRG-3, ABCC5/MRP5, and HRG-7. These discoveries have significantly advanced understanding of heme trafficking and established a paradigm for heme transport in animals. Beyond his work with C. elegans, Dr. Hamza has shown that related nematodes and parasitic helminths do not synthesize heme, similar to Trypanosomes and Leishmania, highlighting potential targets for therapeutic intervention. His research has led to the identification of homologs of heme transporters in humans and parasites that depend on host heme for survival. His work aims to develop inhibitors targeting heme transport pathways in parasites affecting humans, livestock, and plants, as well as in humans with genetic disorders of heme and iron metabolism.

Research topics

• Biology
• Biochemistry
• Chemistry
• Botany
• Organic chemistry
• Genetics
• Cell biology

Selected publications

• A cell-nonautonomous heme acquisition pathway enables erythroid hemoglobinization under stress

  Science · 2026-04-23

  articleOpen accessSenior authorCorresponding

  Heme, an iron-containing cofactor, is synthesized in mitochondria by an eight-enzyme pathway. Although cells were thought to manage heme autonomously, more than 1000 proteins contribute to its production, transport, and regulation. During terminal erythroid differentiation, mitochondria are discarded, yet hemoglobin production continues, which implies a cell-nonautonomous heme supply. We show that, under stress, erythroblasts import heme through the permease heme-responsive gene 1 (HRG1), which localizes to the plasma membrane and accumulates during stress erythropoiesis, the emergency program that expands red cell output. HRG1 loss impaired heme uptake, inhibited terminal erythroid differentiation, and caused anemia. In β-thalassemic mice, partial HRG1 loss reduces ineffective erythropoiesis, underscoring the importance of balanced heme import. These findings reveal intercellular heme sharing and identify HRG1 as a potential therapeutic target in hemoglobinopathies.

  PublisherDOI

• Heme Iron Polypeptide Resolves Iron-deficiency Anemia in Rats and Mice

  Biological Trace Element Research · 2026-04-15

  articleOpen access

  Dietary iron exists mainly as non-heme iron (NHI) and heme iron (HI). Mechanisms of NHI absorption have been recently revealed, but details of HI absorption remain uncertain. Heme is likely absorbed by receptor-mediated endocytosis, but to date, no receptor (or transporter) has been identified. Within enterocytes, heme may be catabolized by heme oxygenase in the ER, thus liberating ionic iron that then joins the labile cytosolic iron pool. One limiting factor in HI absorption research has been the lack of tractable experimental models. We addressed this shortcoming by establishing a nutritional paradigm that enables investigation of this process using pre-clinical rat and mouse models (JCI Insight. 2025;10(11):e184742). The approach utilized specially formulated diets containing lyophilized porcine RBCs that contained ~ 85% HI and 15% NHI. We have expanded upon these studies here to include heme iron polypeptide (HIP) as an iron source (Proferrin; Colorado Biolabs). HIP, a partially proteolyzed form of hemoglobin, is highly enriched for HI (~ 93% HI, 7% NHI). We again utilized a classic depletion/repletion experimental design in SD rats and C57BL/6 mice to compare outcomes when using three AIN-93-based test diets with ~ 50 ppm total iron: a HIP diet, a NHI diet containing FeSO4 and a HI-enriched diet formulated with porcine RBCs. Outcomes notably showed that all three experimental diets similarly corrected the anemia and normalized erythropoietic biomarkers in iron-depleted rats and mice within the 24-28-day test periods. These results solidify the concept that laboratory rodents are useful in vivo models to study intestinal HI absorption and utilization.

  PublisherOA PDFDOI

• A cell-nonautonomous heme acquisition pathway enables erythroid hemoglobinization under stress

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-11

  articleOpen accessSenior authorCorresponding

  Heme, an iron-containing cofactor, is synthesized in mitochondria by an eight-enzyme pathway. Although cells were thought to manage heme autonomously, over 1,000 proteins contribute to its production, transport, and regulation. During terminal erythroid differentiation, mitochondria are discarded yet hemoglobin production continues, implying a cell-nonautonomous heme supply. We show that, under stress, erythroblasts import heme through the permease Heme Responsive Gene 1 (HRG1), which localizes to the plasma membrane and accumulates during stress erythropoiesis, the emergency program that expands red cell output. HRG1 loss impaired heme uptake, inhibited terminal erythroid differentiation, and caused anemia. In β-thalassemic mice, partial HRG1 loss reduces ineffective erythropoiesis, underscoring the importance of balanced heme import. These findings reveal intercellular heme sharing and identify HRG1 as a potential therapeutic target in hemoglobinopathies.

  PublisherOA PDFDOI

• The UTRs of Leishmania donovani vary in length and are enriched in potential regulatory structures

  PLoS Pathogens · 2026-03-06

  articleOpen access

  Leishmania spp. regulate gene expression posttranscriptionally, yet untranslated regions (UTRs) that can affect mRNA stability and translation remain poorly delineated. We generated a de novo assembled genome for Leishmania donovani strain 1S2D (Ld1S) using PacBio HiFi and characterized the transcriptomes of promastigotes and axenic amastigotes with Oxford Nanopore direct RNA sequencing. The genome assembly consists of 65 scaffolds totaling ~33.3 Mb. Structural comparisons to LdBPK282A1 revealed numerous rearrangements, including genes reshuffled among polycistronic transcription units and validated by RNA sequencing of polycistronic reads. Promastigote and amastigote RNA sequencing produced 469,010 and 46,729 monocistronic reads containing a spliced-leader and a polyA tail sequences, defining 8,479 transcripts and supporting 7,415 of the 7,969 annotated protein-coding genes, as well as 604 putative long non-coding RNAs. We annotated UTRs for 4,921 genes and observed that putative RNA G-quadruplexes were markedly enriched in these regions. We also noted that 31.9% and 11.5% of genes were expressed into multiple isoforms in promastigotes and amastigotes, respectively. Collectively, these data provide a genome-wide annotation of L. donovani genes and their UTRs and reveal widespread and stage-specific UTR length polymorphisms and, overall, points to an important role of 3' UTRs in post-transcriptional regulation in L. donovani.

  PublisherDOI

• Heme and immunity: The heme oxygenase dichotomy

  Journal of Inorganic Biochemistry · 2025-02-06 · 5 citations

  reviewOpen accessSenior authorCorresponding

  Heme, an iron containing organic ring, is required for a diverse range of biological processes across all forms of life. Although this nutrient is essential, its pro-inflammatory and cytotoxic properties can lead to cellular damage. Heme oxygenase 1 (HO-1) is an endoplasmic reticulum (ER)-anchored enzyme that degrades heme, releasing equimolar amounts of carbon monoxide (CO), biliverdin (BV), and iron. The induction of HO-1 by heme presents an interesting dichotomy in the cell: CO and BV possess anti-inflammatory and antioxidant properties while free iron can be detrimental as it can generate hydroxyl radicals through the Fenton reaction. The heme/HO-1 axis is tightly regulated, and can influence cell fate, local tissue environments, and disease outcomes during pathogen infection. In this review we explore the role of heme during macrophage polarization and its ability to act as an immune activator while also examining the contribution of HO-1 and heme during infections with intracellular and extracellular pathogens. We highlight work from the emerging field of nutritional immunity of heme and iron, and how the substrates and byproducts of heme metabolism via HO-1 can be beneficial to the host or the pathogen depending on the context. Damaged or senescent red blood cells are erythrophagocytosed by macrophages. Heme is released from hemoglobin and is transported into the cytosol by heme responsive gene 1 (HRG1) where it is degraded by heme oxygenase (HO-1). Byproducts of HO-1 produce anti-inflammatory mediators. Heme can also activate toll-like receptor 4 (TLR-4) mediated production of pro-inflammatory mediators. • Heme is an essential nutrient that has pro-inflammatory and cytotoxic properties. • Heme oxygenase 1 is an endoplasmic reticulum-anchored enzyme that degrades heme. • Heme degradation products can possess anti-inflammatory and antioxidant properties. • Heme can polarize macrophages and act as an immune activator during infections.

  PublisherDOI

• Myocarditis could be the first presentation of arrhythmogenic cardiomyopathy

  Archives of cardiovascular diseases · 2025-01-01

  article1st authorCorresponding
  PublisherDOI

• The UTRs of Leishmania donovani vary in length and are enriched in potential regulatory structures

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-22

  preprintOpen access

  Abstract Leishmania spp. regulate gene expression largely post-transcriptionally, yet untranslated regions (UTRs) remain poorly delineated. We generated high-quality genome and transcriptome datasets for Leishmania donovani strain 1S2D (Ld1S) by combining PacBio HiFi de novo assembly with Oxford Nanopore direct RNA sequencing of promastigotes and axenic amastigotes. The genome assembly consists of 65 scaffolds totaling ∼33.3 Mb. Structural comparisons to LdBPK282A1 revealed numerous rearrangements, including some reshufling genes among polycistronic transcription units and validated by polycistronic reads from RNA sequencing. Promastigote and amastigote RNA sequencing produced 469,010 and 46,729 monocistronic reads containing a spliced-leader and a polyA tail sequences, defining 8,479 transcripts and supporting 7,415 of the 7,969 annotated protein coding genes, as well as 604 putative long non-coding RNAs. We annotated UTRs for 4,921 genes and observed that putative RNA G-quadruplexes were markedly enriched in UTRs. We also noted that 31.9% and 11.5% were expressed into multiple isoforms in promastigotes and amastigotes, respectively. Collectively, these data provide a comprehensive annotation of L. donovani genes and their UTRs and reveal widespread and stage-specific UTR length polymorphisms, and, overall, points to an important role of 3’ UTR in post-transcriptional regulation in L. donovani . Author Summary Leishmania donovani parasites cause visceral leishmaniasis, a deadly disease affecting hundreds of thousands of people worldwide. Unlike most eukaryotes, these parasites do not regulate their genes mainly at the level of transcription. Instead, control happens after the genes are transcribed, and much of this regulation depends on regions of RNA that are not translated into protein, called untranslated regions (UTRs). However, UTRs in Leishmania have remained poorly characterized. Here we generated high-quality genome and transcriptome resources for a clinical strain of L. donovani . By combining state-of-the-art long-read sequencing technologies, we precisely mapped thousands of UTRs and discovered that many genes produce transcripts with variable UTR lengths that differ between parasite life stages. We also found that UTRs are enriched in RNA structures called G-quadruplexes, which are known to influence gene regulation. These findings provide the most comprehensive view to date of UTRs in Leishmania and highlight their central role in controlling how genes are expressed during the parasite’s life cycle. Our work lays a foundation for future studies aimed at understanding parasite biology and identifying new targets for intervention.

  PublisherOA PDFDOI

• A global survey of taxa-metabolic associations across mouse microbiome communities

  Cell Host & Microbe · 2025-11-01 · 3 citations

  articleOpen access

  Host-microbiota mutualism is rooted in the exchange of dietary and metabolic molecules. Microbial diversity broadens the metabolite pool, with each taxon contributing distinct compounds in varying proportions. In the human microbiome, high variability in consortial composition is largely compensated by similar metabolic functions across different taxa. However, the extent of compensation in lower diversity mouse models, and whether vivaria are metabolically equivalent, is unknown. We provide a searchable resource of microbiome composition variability across 51 murine vivaria and 12 wild mouse colonies worldwide, with vivarium-specific variants mapped according to predicted 3D structures for each microbial species. Our matched metabolomics data show that realized metabolic potential has relatively low variability, providing functional evidence for metabolic compensation. Additionally, variability is related to taxonomic composition rather than vivarium, revealing taxa-metabolite associations that are potentially relevant to phenotypic differences between vivaria. Collectively, this resource offers tools to strengthen microbiome studies and collaborative science.

  PublisherDOI

• Development of rat and mouse models of heme-iron absorption

  JCI Insight · 2025-06-08 · 3 citations

  articleOpen access

  Heme iron (HI), derived principally from hemoglobin (Hb) in animal foods, is a highly bioavailable source of dietary iron for humans. Despite several decades of focused research, however, molecular mechanisms governing HI absorption remain undefined. Previous studies in mice and rats have not produced a consensus, definitive model of efficient HI absorption/utilization. We hypothesized that a nutritional approach, using semipurified, HI-containing diets, could be utilized to establish a tractable rodent model of HI absorption that could ultimately be employed to test the roles of receptors, transporters, and enzymes using genetic engineering technology. Experiments were designed to assess HI utilization by feeding animals AIN-93G-based, HI-enriched experimental diets formulated with lyophilized porcine RBCs, containing approximately 85% HI and 15% nonheme iron (NHI). Total iron was within the physiological range (50-75 ppm) and precisely matched NHI control diets containing ferrous sulfate were utilized as comparators. Notably, in Sprague-Dawley (S-D) rats and C57BL/6 (B6) mice, dietary HI effectively (a) resolved iron-deficiency anemia; (b) supported normal pregnancy, lactation, and neonatal development; and (c) contributed to iron loading in Hamp-KO mice and rats (modeling hereditary hemochromatosis). A nutritional paradigm has thus been established that facilitates investigation into mechanisms of HI absorption by S-D rats and B6 mice.

  PublisherDOI

• Author Correction: HRG-9 homologues regulate haem trafficking from haem-enriched compartments

  Nature · 2024-12-12

  erratumOpen access
  PublisherOA PDFDOI

Recent grants

• Selective inhibitors of Heme Transporters as Antiparasitic Agents

  NIH · $702k · 2015–2019

• Inter-organ signaling in heme metabolism and organismal homeostasis.

  NIH · $5.4M · 2006–2026

• NIH Grant R21NS075650

  NIH · $159k · 2013

• The Transport of Nutritional Heme in Animal Development

  NIH · $3.6M · 2010–2022

• NIH Grant R21DK068260

  NIH · $316k · 2006

Frequent coauthors

• Anita U. Rao

  University of Maryland, College Park

  28 shared

• Emmanuel Lesuisse

  Institut Jacques Monod

  25 shared

• Lynn K. Carta

  Agricultural Research Service

  25 shared

• Xiaojing Yuan

  University of Maryland, Baltimore

  22 shared

• Jonathan D. Gitlin

  11 shared

• Caiyong Chen

  Zhejiang University

  10 shared

• Michael Krause

  National Institutes of Health

  10 shared

• Tamika K. Samuel

  University of Maryland, College Park

  8 shared

Education

• Postdoctoral Fellow/Instructor, Pediatrics - cell biology

  Washington University in Saint Louis School of Medicine

  2002

• Ph.D., Biochemistry

  University at Buffalo State University of New York School of Medicine and Biomedical Sciences

  1997

• M.Sc., Biochemistry

  University of Bombay

  1991

• B.Sc., Biochemistry

  University of Bombay

  1989

Awards & honors

• AGNR Awards
• Excellence in Extension Award
• Excellence in Instruction Award
• Excellence in Research Award