Our Current Research and Innovation Efforts
The Chiarle Laboratory is interested in genetic mechanisms and therapy of cancers. By exploiting genome-wide approaches, we aim at understanding the general principles that govern the formation of chromosomal translocations in cancers and their therapeutic vulnerabilities. In translational efforts, we are developing innovative immunotherapies for tumors, including a vaccine to elicit strong and specific immune responses against tumors that express ALK and ALK-specific chimeric antigen receptor (CAR) T cells.
The Fleming Laboratory is interested in three general areas: 1) understanding how mammals acquire and utilize iron for the purpose of heme synthesis and erythropoiesis, 2) the genetics of rare inherited blood diseases, including genetic iron overload and iron deficiency, congenital anemias (particularly congenital sideroblastic anemia) and other cytopenias, as well as bone marrow failure disorders, and 3) the role of the ubiquitin-proteasome system (UPS) in modifying the erythroid proteome during terminal erythropoiesis. To investigate these areas, we take two general approaches. First we using next generation sequencing techniques to identify the genes underlying mouse and human disease phenotypes. Second, using targeted mutagenesis in the mouse, we are studying proteins implicated in systemic, intracellular and erythroid iron homeostasis, and the UPS.
The Haynes Laboratory engages in basic and translational science to better understand biological vulnerabilities that contribute to the Sudden Infant Death Syndrome (SIDS) and to elucidate means by which we can ultimately prevent this death from occurring. We focus on two overarching questions: (1) what are the pathogenic mechanisms underlying SIDS and; (2) can we utilize biomarkers of these mechanisms to identify living infants most at risk for SIDS? Through neurobiologic, genomic, proteomic, metabolomic, and physiologic approaches, our research includes unique collaborations with clinicians developing translational approaches to Sudden and Unexpected Death in Pediatrics and scientists studying animal models related to SIDS.
The Kanarek Laboratory is interested in folate metabolism. It is surprising that this essential vitamin, so famous for its key role in development, hematopoiesis and cancer progression, is still a mystery when it comes to its cellular and whole-body sensing and homeostasis.
The Kanarek lab applies genetic perturbations, biochemical assays, molecular biology, functional genomic screens, and metabolite profiling by mass spectrometry in cell-culture systems and in vivo to study basic folate biology including folate metabolism, folate-related signal transduction, the oncogenic role of folate and folate homeostasis in normal physiology and pathological conditions.
To learn more please visit https://www.kanareklab.com/
The Lehtinen Laboratory is fascinated by how the choroid plexus – cerebrospinal fluid (CSF) system instructs brain development and lifelong heath. Recent work in the lab has focused on investigating how the CSF proteome is regulated by the choroid plexus, a tissue located in each ventricle in the brain. We have produced a cellular and spatial map of the choroid plexus using sequencing approaches. A major goal is to adapt emerging imaging technologies in order to access and control CSF production in vivo. With this toolkit, we are addressing exciting questions about normal brain development, and exploring disease mechanisms underlying neurodevelopmental as well as age-associated neurologic conditions including hydrocephalus, mental health, and cancer.
The Simoes-Costa lab
The Simoes-Costa lab focuses on decoding the molecular programs that orchestrate cell differentiation in the vertebrate embryo. We employ functional genomics to characterize the gene regulatory circuits that control cell state transitions during embryonic development. We are particularly interested in how networks of regulatory genes operate in space to divide the early embryo into distinct fields of progenitor cells. Ultimately, our goal is to recapitulate developmental programs in vitro to engineer cell types for repair and regeneration.
Our model of choice is the neural crest, a stem cell population that plays a crucial role in the genesis of the vertebrate body plan. Neural crest cells emerge from the central nervous system to give rise to intricate structures like the craniofacial skeleton and the peripheral ganglia. They have served as an essential developmental model system due to their motility and ability to form various cell types. We approach the neural crest as a system for integrative biology, surveying how multiple layers of regulation work together to control cell identity and behavior.
Dr. Steen is the principal investigator of a state-of-the-art mass spectrometry-based proteomics laboratory. His group develops and applies quantitative proteomics methods to analyze a wide range of body fluids to map the molecular basis of the pathophysiological processes of a disease and/or to identify disease-relevant biomarkers in primary human specimens. The Steen group is particularly interested in establishing high-throughput proteomics pipelines to analyze hundreds or even thousands of samples in the context of various inflammatory, infectious, and neurodegenerative diseases.
As a member of the NIAID-funded Human Immunology Project Consortium (HIPC), Immune Development in Early Life (IDEaL) and Immunophenotyping Assessment in a Covid-19 Cohort (IMPACC) programs, and the NCI/NIDDK-funded Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) consortium, his pipeline has been widely used on large cohorts with thousands of samples. A key methodology published in 2023 in Science Advances allows for extremely robust deep plasma proteomics at an unprecedented throughput of 60 to 100 samples per day. This key methodology was validated on more than 3,200 samples from the IMPACC cohort.
Other research efforts from the Steen group are dedicated to developing sample-sparing proteomics platforms to enable the analysis of body fluid samples from the smallest, frailest patient population: extremely low gestational age preemies. These efforts are geared toward better understanding the molecular determinants of health and disease/complications in neonatal intensive care units. Finally, the Steen group also works on maximizing the information content that can be extracted from LC/MS-based discovery proteomics. While most proteomics studies take a more protein-centric approach, the Steen group focuses on the qualitative and quantitative information associated with the individual peptides providing insights into protein modifications and splice events.