Genetics and genomics of iron metabolism defects
Associate Professor of Medical Genetics at Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, researcher at CEINGE Biotecnologie Avanzate Franco Salvatore, and head of the analytical phase at the Medical genetics of diseases of the developmental age LAB CEINGE.
Since 2011, Immacolata Andolfo has focused her research on the genetic bases of complex disorders and Mendelian diseases, particularly hereditary anemias and iron metabolism defects. She specialized in anemias caused by membrane defects, with a key focus on hereditary stomatocytosis.
Between 2012 and 2015, she contributed as the first author to the identification of the causative genes of these conditions (PIEZO1, KCNN4, ABCB6). During her postgraduate and Ph.D. studies at the University Federico II of Naples, she gained expertise in research projects on genotype-phenotype correlation in hereditary membrane transport defects, becoming a leading expert in the genetics of dehydrated hereditary stomatocytosis and PIEZO1.
As a postdoctoral researcher (2017-2020) she conducted numerous studies on molecular genetics and pathophysiology of dehydrated hereditary stomatocytosis and other hereditary anemias.
In 2018, she began studying iron metabolism and identified PIEZO1 as a key player in this process. Her collaboration with Nobel laureate Professor Ardem Patapoutian led to groundbreaking work published in Cell.
She is a member of the Italian Society of Thalassemias and Hemoglobinopathies (SITE). She is also a member of the European Hematology Association (EHA), where he holds a position on the steering committee of the "Specialized working group". Additionally, she is a member of the Italian Society of Human Genetics (SIGU) and a member of EuroBloodNet, the European Reference Network (ERN) for Rare Hematological Diseases.
In 2021, she became a researcher in the tenure track in medical genetics at the Department of Molecular Medicine and Medical Biotechnologies, Università degli Studi di Napoli Federico II. Since 2024, she has been an Associate Professor of Medical Genetics at the same department.
From 2001 she also directed the analytical phase at the Medical genetics of diseases of the developmental age LAB CEINGE.
Immacolata Andolfo is the author of 124 publications, with 7414 citations, and an h-index of 39 (Google Scholar update on February 2025).
Hereditary defects of red blood cells and iron metabolism represent a very heterogeneous class of diseases and genetic syndromes, characterized by high genetic and phenotypic variability. In recent years, Andolfo's group has focused on studying hereditary dehydrated stomatocytosis and its main causative gene, PIEZO1. This gene encodes a mechanoreceptor involved in several biological processes essential for life. Recent research has focused on the role of PIEZO1 in the regulation of erythroid differentiation and iron metabolism, using various omics technologies such as transcriptomics, genomics, proteomics, and metabolomics in ex vivo, in vitro, and murine models of the disease.
1. Exploring mTOR pathway in PIEZO1 activating signaling in both hepatocytes and macrophages by in vitro and in vivo models.
2. Exploring the role of PIEZO1 in hereditary hemochromatosis
3. Dissecting the role of PIEZO1 in liver sinusoidal endothelial cells to identify new druggable targets for iron overload
4. Drug repositioning in erythroid and hepatic models of dehydrated hereditary stomatocytosis to find new therapeutic strategies
Barbara Eleni Rosato – researcher in tenue track of Medical Genetics at dipartimento di Medicina Molecolare e Biotecnologie mediche, Università degli studi di Napoli Federico II
Vanessa D’Onofrio post-graduate student of residency school of medical genetics at Università degli studi di Napoli Federico II
Federica Maria Esposito PhD student of Molecular Medicine and medical biotecnologies at Università degli studi di Napoli Federico II
Alessia Perrotta post-graduate researcher at dipartimento di Medicina Molecolare e Biotecnologie mediche, Università degli studi di Napoli Federico II
Sara Esposito Medical Biotechnology graduating student at Università degli studi di Napoli Federico II
1: Rosato BE, D'Onofrio V, Marra R, Nostroso A, Esposito FM, Iscaro A, Lasorsa VA, Capasso M, Iolascon A, Russo R, Andolfo I. RAS signaling pathway is essential in regulating PIEZO1-mediated hepatic iron overload in dehydrated hereditary stomatocytosis. Am J Hematol. 2025 Jan;100(1):52-65. doi: 10.1002/ajh.27523. PMID: 39558179.
2: Pinto VM, Russo R, Quintino S, Rosato BE, Marra R, Del Giudice F, Mogni M, Maffei M, Iolascon A, Forni GL, Andolfo I. Coinheritance of PIEZO1 variants and multi-locus red blood cell defects account for the symptomatic phenotype in beta-thalassemia carriers. Am J Hematol. 2023 Jun;98(6):E130-E133. doi:10.1002/ajh.26901. PMID: 36882369.
3: Ma S, Dubin AE, Zhang Y, Mousavi SAR, Wang Y, Coombs AM, Loud M, Andolfo I, Patapoutian A. A role of PIEZO1 in iron metabolism in mice and humans. Cell. 2021 Feb 18;184(4):969-982.e13. doi: 10.1016/j.cell.2021.01.024. PMID: 33571427
4: Andolfo I, Rosato BE, Manna F, De Rosa G, Marra R, Gambale A, Girelli D, Russo R, Iolascon A. Gain-of-function mutations in PIEZO1 directly impair hepatic iron metabolism via the inhibition of the BMP/SMADs pathway. Am J Hematol. 2020 Feb;95(2):188-197. doi: 10.1002/ajh.25683. Epub 2019 Dec 9. PMID: 31737919.
5: Andolfo I, Alper SL, De Franceschi L, Auriemma C, Russo R, De Falco L, Vallefuoco F, Esposito MR, Vandorpe DH, Shmukler BE, Narayan R, Montanaro D, D'Armiento M, Vetro A, Limongelli I, Zuffardi O, Glader BE, Schrier SL, Brugnara C, Stewart GW, Delaunay J, Iolascon A. Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1. Blood. 2013 May 9;121(19):3925-35, S1-12. doi: 10.1182/blood-2013-02-482489. PMID: 23479567.