EDWARD A. DOISY
Department of
Biochemistry & Molecular Biology
EST. 1924
Saint Louis University School of Medicine
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Our Legacy
1 Nobel Laureate
Doisy2 Members, National Academy of Sciences
Doisy, Sly1 Member, National Academy of Medicine
Roth3 Members, American Academy of Arts & Sciences
Doisy, Roth, Shilatifard1 Member, Leopoldina
Kutchan11 Fellows, American Association for the Advancement of Science
Di Cera, Doisy, Elliott, Katzman, Kutchan, Lee, Lodge, McKee, Olson, Shilatifard, Sly4 Members and 1 Fellow, National Academy of Inventors
Chang, Di Cera, Heyduk, Lodge, Pozzi2 Pew Scholars
Cole, Yap
Message from the Chair
Welcome to our website!
We recently celebrated 100 years since the founding of the department in 1924 by Dr. Edward A. Doisy, discoverer of estrogens and recipient of the 1943 Nobel Prize in Physiology or Medicine for his work on the synthesis of vitamin K.
The department has an impressive legacy of excellence that continues to this day, fueled by strategic use of the Doisy Fund that supports our growth.
It is an exciting time to join us as a student, postdoc, or new faculty member.
Thank you for visiting!
Department Stats
External Grant Expenditures
Publications
Department Members
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Doisy Conference on Coagulation
A one-day, free event for students, trainees, and researchers in the biomedical sciences.
Monday, May 5, 2025
Bayer Event Center, MO Botanical Garden
What's News
Congratulations to Suresh Kumar, Ph.D., Postdoctoral Fellow in the lab of Nicola Pozzi, on being…
BMB members will be honored at the Scholarly Works and Grantwinners Reception sponsored by the…
Congratulations to Reza Dastvan, Ph.D., for ranking 24th among all biochemistry PIs in the US,…
BRIMR released their final rankings for 2024. BMB ranked 37th out of 95 Biochemistry departments…
Congratulations to Enrico Di Cera, M.D., Professor and Chair of Biochemistry, Nicola Pozzi, Ph.D., Associate…
Department Committees
Doisy Fund
- Yuna Ayala, Ph.D.
- Ángel Baldán, Ph.D.
- Enrico Di Cera, M.D., Chair
- Kathleen E. Doisy, M.S.
- Oleg Kisselev, Ph.D.
- Krista Lentine, M.D., Ph.D.
- LaChina McCoy
- Eleonore Stump, Ph.D.
Instrumentation and Cores
- Edwin Antony, Ph.D., Chair
- Yuna Ayala, Ph.D.
- Ángel Baldán, Ph.D.
- Michelle Brennan, Ph.D.
- Reza Dastvan, Ph.D.
- Nicola Pozzi, Ph.D.
Training
- Madison Adolph, Ph.D., Co-Director of the BMB Graduate Program
- Yuna Ayala, Ph.D., Chair
- Susana Gonzalo, Ph.D.
- Tomasz Heyduk, Ph.D., Co-Director of the BMB Graduate Program
- LaChina McCoy
BMB Faculty Incentives
SLU Incentives
- F&A Rebate: Percentage of F&A rebated to 2-fund
- Non-salary incentive: Half of salary recovered beyond 50% rebated to 2-fund
- Salary bonus from the faculty compensation plan for faculty who have recovered 50% or more of their total compensation from extramural sources as a 3-year rolling average from preceding FYs
Primary Faculty
- Matching of the SLU F&A rebate
- Salary bonus for faculty with salary recovery from extramural sources of at least 50% (Assistant Professor), 65% (Associate Professor), or 75% (Professor). Salary recovery in excess of these levels will be rebated to a 2- fund for research use
- Salary bonus for any grant, new or renewal, with BMB faculty as the PI, generating full indirect costs, and providing at least 4 years of funding
- Salary bonus for new publications with BMB faculty as the corresponding author in journals with an impact factor greater than 10 and a travel award for the leading author of the publication, if a member of BMB
- Full support of the stipend of Ph.D. and M.D./Ph.D. students for 12 months from the date they pass their qualifying exam
Primary & Secondary Faculty
- Matching of JIT grants from the ICTS
- Student support through the Doisy Scholar Program
Doisy Scholar Program
Doisy Scholars
Biochemistry Ph.D. and M.D./Ph.D. students may be appointed as Doisy Scholars at any time during their training.
- Appointment to Doisy Scholar is recommended by the BMB Training Committee and reviewed for approval by the Chair of BMB.
- Doisy Scholarship is an honor reserved for students who have distinguished themselves academically through course work and have achieved scholarly recognition through peer-reviewed publications and poster/oral presentations at meetings or extramural fellowships.
- The stipend and student fees of a Doisy Scholar are supported in full by the BMB Doisy Fund for 24 months.
Click to read more about our Doisy Scholars.
High Impact Publications
Papers highlighted below were published in journals with an impact factor of 10 or greater.
All papers were published within the past year.
All papers were published within the past year.
Recent Publications
Human lung microvascular endothelial cell protein modification by 2-chlorohexadecanoic acid: RhoA mediates 2-chlorohexadecanoic acid-elicited endothelial activation
Human lung microvascular endothelial cell protein modification by 2-chlorohexadecanoic acid: RhoA mediates 2-chlorohexadecanoic acid-elicited endothelial activation
Chlorolipids are produced during the neutrophil respiratory burst as a result of myeloperoxidase (MPO)-generated hypochlorous acid (HOCl) targeting the vinyl ether bond of plasmalogen phospholipids. The initial products of this reaction are 2-chlorofatty aldehydes (2-ClFALDs), which are subsequently oxidized to 2-chlorofatty acids (2-ClFAs). 2-Chlorohexadecanoic acid (2-ClHA) is the 16-carbon 2-ClFA species, and previous studies have shown that increased levels of plasma 2-ClHA associate with acute respiratory distress syndrome (ARDS)-caused mortality in human sepsis. 2-ClHA causes endothelial barrier dysfunction and increases neutrophil and platelet adherence to the endothelium. In this study, click chemistry analogs of 2-ClHA and hexadecanoic acid (HA) were used to identify proteins covalently modified by 2-ClHA and HA in human lung microvascular endothelial cells (HLMVECs). Eleven proteins were specifically modified by 2-ClHA, and an additional one hundred and ninety-four proteins were modified by both 2-ClHA and HA. STRING analysis of 2-ClHA-modified proteins revealed a network of proteins with RhoA as a hub. RhoA is one of the proteins specifically modified by 2-ClHA and not HA. The RhoA inhibitors, Rhosin and C3, inhibited both 2-ClHA-elicited HLMVEC barrier dysfunction and angiopoietin-2 (Ang-2) release from HLMVEC. Further studies showed 2-ClHA activates HLMVEC RhoA activity. The specificity of the 2-ClHA-RhoA pathway for endothelial activation was further confirmed since HA did not cause HLMVEC barrier dysfunction, Ang-2 release and RhoA activation. Collectively, these studies have identified multiple proteins modified exclusively by 2-ClHA in HLMVECs, including RhoA. These proteomics studies led to the key finding that RhoA is an important mediator of 2-ClHA-caused endothelial barrier dysfunction.
Insulin regulates lymphatic endothelial integrity via palmitoylation
Insulin regulates lymphatic endothelial integrity via palmitoylation
Lipid metabolism plays a critical role in lymphatic endothelial cell (LEC) development and vessel maintenance. Altered lipid metabolism is associated with loss of lymphatic vessel integrity, which compromises organ function, protective immunity, and metabolic health. Thus, understanding how lipid metabolism affects LECs is critical for uncovering the mechanisms underlying lymphatic dysfunction. Protein palmitoylation, a lipid-based post-translational modification, has emerged as a critical regulator of protein function, stability, and interaction networks. Insulin, a master regulator of systemic lipid metabolism, also regulates protein palmitoylation. However, the role of insulin-driven palmitoylation in LEC biology remains unexplored. To examine the role of palmitoylation in LEC function, we generated the first palmitoylation proteomics profile in human LECs, validated insulin-regulated targets, and determined the role of palmitoylation in LEC barrier function. In unstimulated conditions, palmitoylation occurred primarily on proteins involved in vesicular and membrane trafficking, and in translation initiation. Insulin treatment, instead, enriched palmitoylation of proteins involved in LEC integrity, namely junctional proteins such as claudin 5, along with small GTPases and ubiquitination enzymes. We also investigated the role of the long-chain fatty acid transporter CD36, a major mediator of palmitate uptake into cells, in regulating optimal lymphatic protein palmitoylation. CD36 silencing in LECs increased by 2-fold palmitoylation of proteins involved in inflammation and immune cell activation. Overall, our findings provide novel insights into the intricate relationship between lipid modification and LEC function, suggesting that insulin and palmitoylation play a critical role in lymphatic endothelial function.
Kingfisher: An open-sourced web-based platform for the analysis of hydrogen exchange mass spectrometry data
Kingfisher: An open-sourced web-based platform for the analysis of hydrogen exchange mass spectrometry data
Hydrogen-deuterium exchange mass spectrometry (HDX-MS) is now a critical tool in molecular biology and structural proteomics. It is routinely used to probe protein and conformational dynamics through a well-established experiment where amide hydrogens exchange with deuterium atoms in a buffer containing DO. Although there have been numerous advances in the field, data analysis still poses challenges mainly due to the need for manual curation of the data and the lack of standardized statistics and accessible software. In response, we developed Kingfisher, an open-source, user-friendly, web-based solution that facilitates downstream analysis using well-established statistics and provides advanced high-resolution representations of the HDX results. Kingfisher is able to read data directly as exported from common software packages and usually takes less than a minute to run the analysis, without the need to download the raw code or install any software. We foresee Kingfisher as a valuable tool for both newcomers and experts in the field of Hydrogen Exchange Mass Spectrometry. Kingfisher is available to all users as an interactive web application at https://kingfisher.wustl.edu/.
Lupus Anticoagulant and Anti-Prothrombin Antibodies: Embracing the Future
Lupus Anticoagulant and Anti-Prothrombin Antibodies: Embracing the Future
Lupus anticoagulant (LAC) is a well-known laboratory test used to explore potential reasons for the prolongation of phospholipid-dependent coagulation tests. An extended clotting time in a coagulation test typically suggests a bleeding tendency, as the plasma takes longer to clot. However, a positive LAC result, defined as normalization of prolonged clotting time by adding anionic phospholipids in the system, does not necessarily imply this. In fact, quite the opposite is true: a positive LAC often strongly correlates with an increased risk of thromboembolic events. Therefore, despite being conceptually counterintuitive, LAC remains extremely valuable in routine clinical practice for identifying individuals at risk for thromboembolic events. Over the years, various factors have been recognized as potential inducers of LAC, with antiphospholipid antibodies associated with antiphospholipid syndrome (APS) playing a significant role. Today, research indicates that, among antiphospholipid antibodies, those targeting plasma proteins β-glycoprotein I and prothrombin are central to LAC. This article offers a historical perspective on LAC, emphasizing recent developments in anti-prothrombin antibodies, their connection to LAC, and novel detection methods. Our premise is that a deeper understanding of how anti-prothrombin antibodies contribute to LAC and the identification of subpopulations of these antibodies potentially responsible for it in thrombotic APS patients could lead to transformative advancements, offering new strategies for risk stratification and personalized treatments for patients with APS and beyond.
Cryo-EM captures the coordination of asymmetric electron transfer through a di-copper site in DPOR
Cryo-EM captures the coordination of asymmetric electron transfer through a di-copper site in DPOR
Enzymes that catalyze long-range electron transfer (ET) reactions often function as higher order complexes that possess two structurally symmetrical halves. The functional advantages for such an architecture remain a mystery. Using cryoelectron microscopy we capture snapshots of the nitrogenase-like dark-operative protochlorophyllide oxidoreductase (DPOR) during substrate binding and turnover. DPOR catalyzes reduction of the C17 = C18 double bond in protochlorophyllide during the dark chlorophyll biosynthetic pathway. DPOR is composed of electron donor (L-protein) and acceptor (NB-protein) component proteins that transiently form a complex in the presence of ATP to facilitate ET. NB-protein is an αβ heterotetramer with two structurally identical halves. However, our structures reveal that NB-protein becomes functionally asymmetric upon substrate binding. Asymmetry results in allosteric inhibition of L-protein engagement and ET in one half. Residues that form a conduit for ET are aligned in one half while misaligned in the other. An ATP hydrolysis-coupled conformational switch is triggered once ET is accomplished in one half. These structural changes are then relayed to the other half through a di-nuclear copper center at the tetrameric interface of the NB-protein and leads to activation of ET and substrate reduction. These findings provide a mechanistic blueprint for regulation of long-range electron transfer reactions.
Antiphospholipid IgG Certified Reference Material ERM-DA477/IFCC: a tool for aPL harmonization?
Antiphospholipid IgG Certified Reference Material ERM-DA477/IFCC: a tool for aPL harmonization?
The Certified Reference Material (CRM) ERM-DA477/IFCC is a new polyclonal IgG anti-beta2-glycoprotein I (anti-β2GPI) material for the harmonization of the laboratory diagnosis of antiphospholipid syndrome (APS). We evaluated CRM's ability to represent the heterogeneity of APS patient anti-β2GPI antibodies and to calibrate IgG anti-β2GPI methods.
2-Chloro- and 2-Bromopalmitic acids inhibit mitochondrial function in airway epithelial cells
2-Chloro- and 2-Bromopalmitic acids inhibit mitochondrial function in airway epithelial cells
2-Chloropalmitic acid (2-ClPA) and 2-bromopalmitic acid (2-BrPa) increase in inflammatory lung disease associated with formation of hypochlorous or hypobromous acid, and exposure to halogen gases. Moreover, these lipids may elicit cell responses that contribute to lung injury, but the mechanisms remain unclear. Here, we tested the hypothesis that 2-ClPA and 2-BrPA induce metabolic defects in airway epithelial cells by targeting mitochondria. H441 or primary human airway epithelial cells were treated with 2-ClPA or 2-BrPA and bioenergetics measured using oxygen consumption rates and extracellular acidification rates, as well as respiratory complex activities. Relative to vehicle or palmitic acid, both 2-halofatty acids inhibited ATP-linked oxygen consumption and reserve capacity, suggestive of increased proton leak. However, neither 2-ClPA nor 2-BrPA altered mitochondrial membrane potential, suggesting proton leak does not underlie inhibited ATP-linked oxygen consumption. Interestingly, complex II activity was significantly inhibited which may contribute to diminished reserve capacity, but activity of complexes I, III and IV remain unchanged. Taken together, the presented data highlight the potential of 2-halofatty acids to disrupt bioenergetics and in turn cause cellular dysfunction.
Another cryo-EM success: structure of FXIII
Targeting CRM1 for Progeria Syndrome Therapy
Targeting CRM1 for Progeria Syndrome Therapy
Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease caused by progerin, a mutant variant of lamin A. Progerin anchors aberrantly to the nuclear envelope disrupting a plethora of cellular processes, which in turn elicits senescence. We previously showed that the chromosomal region maintenance 1 (CRM1)-driven nuclear export pathway is abnormally enhanced in patient-derived fibroblasts, due to overexpression of CRM1. Interestingly, pharmacological inhibition of CRM1 using leptomycin B rescues the senescent phenotype of HGPS fibroblasts, delineating CRM1 as a potential therapeutic target against HGPS. As a proof of concept, we analyzed the beneficial effects of pharmacologically modulating CRM1 in dermal fibroblasts from HGPS patients and the LMNA mouse, using the first-in-class selective inhibitor of CRM1 termed selinexor. Remarkably, treatment of HGPS fibroblasts with selinexor mitigated senescence and promoted progerin clearance via autophagy, while at the transcriptional level restored the expression of numerous differentially-expressed genes and rescued cellular processes linked to aging. In vivo, oral administration of selinexor to the progeric mouse resulted in decreased progerin immunostaining in the liver and aorta, decreased progerin levels in most liver, lung and kidney samples analyzed by immunoblotting, and improved aortic histopathology. Collectively our data indicate that selinexor exerts its geroprotective action by at least two mechanisms: normalizing the nucleocytoplasmic partition of proteins with a downstream effect on the aging-associated transcriptome and decreasing progerin levels. Further investigation of the overall effect of selinexor on Lmna mouse physiology, with emphasis in cardiovascular function is warranted, to determine its therapeutic utility for HGPS and aging-associated disorders characterized by CRM1 overactivity.
Metabolic dysfunction and insulin sensitizers in acute and chronic disease
Metabolic dysfunction and insulin sensitizers in acute and chronic disease
The concept of insulin resistance has been a major topic for more than 5 decades. While there are several treatments that may impact insulin resistance, this pathology is uniquely addressed by mitochondrially directed thiazolidinedione (TZD) insulin sensitizers. Understanding of this mechanism of action and consideration of 'insulin resistance' as a consequence of metabolic inflammation allows a new paradigm for approaching chronic diseases.
