Graduate students Emily Dennis and Maria Muroch of the McNamara and Bekiranov labs, respectively, published their work “Loss of TET2 increases B-1 cell number and IgM production while limiting CDR3 diversity” in the Journal Frontiers of Immunology, along with several other co-authors.

The team investigated the role of the protein Ten-Eleven Translocation-2 (TET2) in regulating B-1 cells.  They compared wild type mice to mice with a global knockout of TET2 and analyzed numbers of B-1 cells, production of the antibody subtype IgM and gene expression levels.  They found elevated levels of both B-1a and B-1b cells in the peritoneal cavity, bone marrow and spleen.  They also analyzed the expression of receptor proteins by these cells.  Taken together, their study is the first to demonstrate that global loss of TET2 increases B-1 cell number and IgM production and reduces CDR3 diversity, which could impact many biological processes and disease states that are regulated by IgM. You can read more about their work here.

Team Erickson, composed of Loren Erickson, PhD, Coleen McNamara, MD (Carter Center Director, iPRIME Domain Director), and Justin Taylor, PhD tied for first place at the inaugural “Shark Tank” Competition at School of Medicine Retreat.  The competing teams submitted proposals and answered questions from the “Sharks”, proposals were voted on by retreat attendees.  They were awarded $150,000 for their project “Immune Mechanisms of IgE Sensitization to Alpha-Gal”.  You can learn more about the competition at the School of Medicine website here: https://news.med.virginia.edu/research/research-faculty-explore-emerging-approaches-and-biotechnologies/

New research suggests sensitivity to common food allergens such as dairy and peanuts could be an important and previously unappreciated cause of heart disease, and the increased risk for cardiovascular death even includes people without obvious food allergies.

UVA Health scientists and their collaborators looked at thousands of adults over time and found that people who produced antibodies in response to dairy and other foods were at elevated risk of cardiovascular-related death. This was true even when traditional risk factors for heart disease, such as smoking, high blood pressure and diabetes, were taken into account.

“What we looked at here was the presence of IgE antibodies to food that were detected in blood samples,” said researcher Dr. Jeffrey Wilson, an allergy and immunology expert at the University of Virginia School of Medicine. “We don’t think most of these subjects actually had overt food allergy. Thus, our story is more about an otherwise silent immune response to food. While these responses may not be strong enough to cause acute allergic reactions to food, they might nonetheless cause inflammation and over time lead to problems like heart disease.”

Full article at UVA Today Website.

Oom Pattarabanjird, a graduate student in the McNamara lab, reports in Nature Cardiovascular Research on her discovery of the human B cell subtype that produces antibody to target and inactivate inflammatory atherosclerotic antigens.

Atherosclerosis has emerged as a chronic inflammatory disease fueled by neoantigens formed by modification of self proteins, such as the oxidation of low density lipoprotein (LDL). Yet, the identity of the cell responsible for producing these protective antibodies in human has remained elusive. In the most recent edition of the journal, Oom describes novel findings using single cell protein and gene analysis of human circulating immune cells in individuals with severe compared to those with little to no coronary artery disease. She identified that the frequency of the CD24hi Marginal Zone B cells is significantly associated with high levels of the atheroprotective IgM to MDA-LDL, she went on to show that these cells produce IgM to MDA-LDL in vivo using humanized mice. Inhibition of CD24 using genetic approaches or the blocking antibody being studied in clinical trials for cancer, resulted in reduced IgM production and increase in vascular inflammation. Her findings have important implications for potential new therapy development using cells, antibodies, and vaccines for atherosclerosis.

The full text of the article, titled “Human circulating CD24hi marginal zone B cells produce IgM targeting atherogenic antigens and confer protection from vascular disease” can be found here: https://www.nature.com/articles/s44161-023-00356-1.

Article also posted on SOM Medicine in Motion News Website.

Oom Pattarabanjird (MSTP trainee with the McNamara lab) received an award for top poster at the recent Atherosclerosis Gordon Conference in Barcelona for her poster entitled “Human Marginal Zone B cells Produce Atheroprotective IgM and Confer Protection from Vascular Disease.”

Congratulations Oom!!

iPRIME members Dr. Loren Erickson and Dr. John Lukens received an NOA supplement for their project “IgE antibody responses to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal) in murine and human atherosclerosis”.  Congratulations to their team for their excellent work investigating the link between alpha-gal and CVD.  We are excited to see and promote the results of this important study!

Dr. Stefan Bekiranov, one of three PI’s of iPRIME &  Dr. Aidong Zhang, recipient of an iPRIME seed fund, have been awarded an NSF grant titled “An Explainable Machine Learning Platform for Single Cell Data Analysis” — this great work will push immunomedicine forward in amazing ways using novel technology.  Congratulations, Drs. Bekiranov and Zhang!

The immunology, imaging, informatics Precision ImmunoMedicine (iPRIME) initiative announces our iPRIME Fellowship Awards. This award will support innovative collaborative projects between students in biological and medical sciences and students in data science. Proposals may budget up to $15,000 and stipend support for one year.

The goal of our iPRIME Fellowship Awards is to facilitate the training of the next generation of scientists and caregivers prepared to apply precision immunomedicine concepts and approaches to their study and care of patients with cardiovascular disease (CVD). The iPRIME Fellowship Awards will catalyze collaborations between biological science, medicine, engineering, and data science by providing trainee stipend support and project costs.

Students in the biomedical sciences have submitted proposals, outlining their need to collaborate with students in the data sciences and/or computer sciences. Data science students interested in collaborating should contact Dr. Mike Davis, iPRIME Program Administrator at mrd5f@virginia.edu. He will pair you with the student whose project is of interest to you for submission of final proposals. The deadline for the paired proposals is June 2nd, 2023.

You can learn more at https://iprime.virginia.edu/iprime-fellowship-awards/

Brett Ransegnola (McNamara lab) and Meritxell Nus (Mallat lab in Cambridge, UK) have been awarded a $50K Leducq Transatlantic Network of Excellence to study the role of Id3 in marginal zone B cells.   They recently met in NYC with the “B cell and Cardiovascular Diseases” Leducq International ResearchTeam to discuss their collaborative science, and get in a little sightseeing.

Congratulations Brett and Meritxell!