Irene Chernova, MD PhD
2021 Recipient of the Gary S. Gilkeson Career Development Award
Title of Project: The Role of the Ion Microenvironment on B cell Survival and Function in SLE
Mentor: Joseph Craft, MD
About the Researcher: Irena Chernova, MD, PhD, received her undergraduate degree at the University of Pennsylvania, where she was part of the research honors program and worked in a monocyte (innate immune cell) biology lab for three years.
Dr. Chernova’s ongoing interest in immunology led her to pursue an MD/PhD program at the University of Pennsylvania where her PhD thesis examined the nature of the bone marrow plasma cell pool. Plasma cells are the antibody-producing factories of the body and are crucial players in most areas of immunology: vaccines, immunity to infection and autoimmunity. Dr. Chernova’s work examined some basic assumptions about the biology of these cells and identified a large pool of short-lived plasma cells in the bone marrow, contradicting long-standing dogma. Her early findings have potentially wide-ranging implications including in the field of B cell-depleting therapies in lupus.
This work and related graduate school projects have resulted in 4 publications as well as a competitive fellowship from the NIH. Since completing her PhD, Dr. Chernova graduated from medical school with honors and completed her residency training in Internal Medicine at Yale New Haven Hospital and a fellowship in clinical Nephrology; she is currently board-certified in both specialties.
Dr. Chernova now works in the laboratory of Joseph Craft, MD, where she has been investigating how immune cells are able to survive in the kidneys of mice and humans with lupus. She currently spends most of her time engaged in direct basic science research including the design, execution, and analysis of experiments. Her clinical responsibilities are limited to attending on the nephrology consult service a few weeks a year, but she remains an active participant in numerous weekly nephrology conferences.
Dr. Chernova hopes to continue to develop her scientific skillset and to transition to an independently funded physician-scientist investigator in the next 2-4 years.
Systemic lupus erythematosus (SLE, lupus) is characterized by immune cell dysregulation including abnormalities in B lymphocytes, the antibody producing cell lineage of the immune system. In fact, therapies focused on depleting B cells are the mainstay of lupus treatment. However, these treatments are associated with side effects including lowered immune function and thus more targeted B cell therapies are needed. One aspect of B cell biology in SLE that is poorly characterized are the interactions of these cells with their organ environments. In the kidney, one of the major organs affected by SLE, B cells have to face a high sodium (Na+) environment and recent research suggests that Na+ content is also higher in organs such as skin in lupus patients as compared to healthy controls. Na+ content of organs like the spleen, where B cells reside, is unknown. My data show that changing the Na+ concentration in the kidney affects the survival of the B cells and may help improve kidney inflammation. I have identified a molecule responsible for sodium and potassium transport, Na+-K+-ATPase, as a likely key player mediating this effect, but many questions remain about the pathways inside the cell that are activated when a B cell is faced with a high salt environment. In my research I will: 1) quantitate the Na+ content of immune organs such as the spleen and 2) define the molecular pathways operating in B cells when they are exposed to high sodium (either in a dish or taken out of a “salty” organ). I hope that understanding these environments and molecular mechanisms can help design more targeted B cell therapies for SLE.