Anastasia Nijnik

We study the biology of hematopoietic stem cells (HSCs) and the regulation of blood and immune cell production in health and disease, focusing specifically on the regulation of gene expression, and the transcriptional and epigenetic mechanisms. Our work has broad implications for the understanding of disorders of bone marrow, blood, and immune system, including bone marrow failures, primary immunodeficiencies, inflammatory disorders, and hematologic malignancies.

I. MYSM1 in Hematopoiesis and Hematopoietic Stem Cell Function: We have demonstrated that the chromatin-binding deubiquitinase MYSM1 is an essential transcriptional regulator of HSC function and leukocyte development. In recent work, we characterized the cross-talk between MYSM1 and the p53 stress response pathway, and analyzed the genes regulated by MYSM1 in HSCs. We are currently analyzing the MYSM1 regulated checkpoints in hematopoiesis and immunity, the molecular mechanisms of MYSM1 activity in these systems, and the pathology of the human MYSM1 deficiency syndrome. The work relies on molecular biology, genetics and bioinformatics, transgenic mouse models, and work with patient samples.

II. BAP1 in the Regulation of B cell Development and Humoral Immune Response: Our team is exploring the role of other nuclear deubiquitinases in B cell development and humoral immune response.

III. Hematopoiesis and Inflammatory Stress: We are exploring HSC dysfunction in rheumatoid arthritis, a chronic systemic inflammatory disorder that affects one in a hundred adults in Canada. We hypothesize that long-term epigenetic changes in HSCs contribute to the altered immune cell production and disease persistence in this disorder. The research program is conducted in close collaboration with Dr. Ines Colmegna and Dr. David Langlais. We are also engaged in a collaborative research program, addressing the mechanisms of inflammatory lung disease in systemic autoimmune rheumatic diseases.

IV. Hematopoiesis and Genotoxic Stress: We are exploring hematopoietic responses to genotoxic stress, and the roles of p53-dependent transcriptional programs and p53-independent mechanisms in this response. The work has implications for the understanding of bone marrow damage in the context of cancer radiotherapy.