Dr. Yvette Yien is an Assistant Professor in the Department of Biological Sciences at the University of Delaware. Dr. Yien grew up in sunny Singapore, where she received her B.Sc. in Life Sciences from the National University of Singapore. During her undergraduate work, she carried out research in the field of x-ray crystallography. This research experience sparked a life-long interest in the role of protein complexes and protein-protein interactions which persists to this day in her own lab. Initially, she was convinced that she wanted to study protein biochemistry until a friend reviewed an entire semester of cell biology lectures that she had skipped right before the test. During this cramming session, she was won over by the beauty of the apoptosis pathway and promptly joined the lab of Dr. Victor Yu at the Institute of Molecular and Cellular Biology to work on the biochemistry of mitochondrial apoptosis pathway proteins. The year she spent in Dr. Yu’s lab sparked a life-long fascination with cell biology, and shaped her approach of identifying problems in vivo, and solving them in vitro. Dr. Yien moved to the US in 2004 and entered the Ph.D. program in Biomedical Sciences at the Mount Sinai School of Medicine in New York City with the goal of learning how cells develop. She worked with Dr. James Bieker, who discovered the Erythroid Kruppel Life Factor, EKLF/KLF1, a master regulator of erythroid transcription and globin switching. KLF1 turned out to be the founding member of the vertebrate KLF family of zinc-finger transcription factors, which regulate a wide range of critical processes such as development, cell death and proliferation. Dr. Yien investigated how the function of EKLF/KLF1 could be modulated in a context-specific manner during erythroid differentiation. During her studies, she observed that EKLF splicing was altered in the bone marrows of pregnant mice and in murine fetal livers. This made her wonder if pregnancy caused adaptive changes in erythropoiesis to meet the requirements of the pregnant female and developing fetus. This fascination with sex-specific regulation of hematopoiesis has persisted and is one of the projects in the Yien lab.
During graduate school, Dr. Yien attended a research seminar by Dr. Trista North on the identification of the PGE2/Wnt pathway as a regulator of hematopoietic stem cells. This seminar opened up the possibility of doing in vivo genetic and imaging experiments in zebrafish that were not possible in mice. Further, she realized that zebrafish is an excellent model organism in which to examine how cellular development occurs within an organismal context. Excited by these possibilities, Dr. Yien left for Boston in 2012 to work on the role of mitochondrial iron metabolism in erythroid cell biology in Barry Paw’s zebrafish lab at Brigham and Women’s Hospital. Her research showed that erythroid cells expressed specialized, mitochondrial membrane proteins which increase the rate transport of heme intermediates and iron during terminal erythroid differentiation. Further, she identified CLPX as a regulator of heme synthesis in vertebrates. Her work in these areas earned her a Ruth L. Kirschstein National Research Service Award (F32) and a K01 career development award from NIH/NIDDK.
Dr. Yien started her lab in 2017 at the University of Delaware with the overarching goal of understanding how cells couple nutrient metabolism with cell-type specific requirements. Although most cells types require the essentially same nutrients for their survival, the specific quantities and fates of these nutrients vary among different cell types as different cells utilize nutrients in varying ways to carry out their specialized functions. One such nutrient that carries out many ubiquitous, life-essential redox reactions in cells in key processes such as such as respiration, maintenance of the circadian rhythm, and detoxification, is iron. Iron also plays a central role in cell-specific processes such as dopamine production within the dopaminergic neuron and oxygen transport by red blood cells. Iron requirements and utilization in different cell types differ widely. For instance, developing erythroid cells, which synthesize 90% of the body’s heme for hemoglobin production, transport massive quantities of iron and rapidly process them into heme. This requires expression of erythroid-specific iron transporters and other proteins which increase the activities of heme synthesis enzymes. Deficiencies in these proteins cause hemoglobinzation defects and developmental defects. Other tissues, such as the liver, utilize iron for the formation of iron-sulphur clusters, which play a key role in mitochondrial respiration, and for synthesis of liver cytochromes. The processes that govern iron fate and which couple the rate of iron uptake to its utilization are mostly unknown. Identification of these regulatory mechanisms is a central goal of the lab.
Currently, the specific goals of the Yien lab are: 1. To interrogate how iron transport and fate is coupled with to cellular requirements, and to exploit this knowledge to understand mechanisms of hematologic physiology and disease. The lab hypothesizes that this occurs by the functional and structural interaction of iron transport proteins and heme metabolome with the mitochondrial homeostasis machinery, which may allow crosstalk between iron metabolism with other nutrient metabolism pathways. 2. To understand how iron is utilized during tissue development, particularly in pathways required for terminal erythroid differentiation and liver development. 3. To elucidate how pregnancy causes adaptive changes in maternal bone marrow hematopoiesis and iron metabolism, increasing erythroid cell production necessary to keep up with increased maternal blood volume, placental function, and fetal iron requirements. The lab employs a broad range of model systems and techniques to solve these problems, including yeast and mammalian cell culture, as well as zebrafish and mouse animal models; this is complemented by biochemical techniques such as metabolic labeling, heme synthesis pathway enzymatic assays and metabolomics (the latter two techniques conducted at the University of Utah). Their long-term goal is to exploit their knowledge of tissue-specific regulation of iron metabolism to more generally understand how nutrient metabolism is regulated in a cell-specific contexts. The work of the lab is currently funded by a P01 subproject award from the NHLBI, an R35 award from NIGMS, an NIDDK R03, pilot and feasibility grants from the NIDDK administered through Indiana University and the Center for Iron and Heme Disorders at the University of Utah, and a Cooley’s Anemia Foundation fellowship.
In addition to her interests in iron metabolism, mitochondrial biology, and pregnancy, Dr. Yien is also enthusiastic about trainee development and passionate about increasing diversity in the scientific workforce, and accessibility to healthcare for under-served populations. One of the things her lab does is to focus on research problems that disproportionately affect women and children. Most of Dr. Yien’s undergraduates have won research awards, and her first postdoc, Dr. Mark Perfetto, was selected for a postdoc exchange program at the Center of Iron and Heme Disorders at the University of Utah. She is actively recruiting postdoctoral fellows and graduate students who are looking to pursue challenging questions in a supportive and diverse research environment. More information about the lab can be found here: https://www.bio.udel.edu/people/yyien.