Roland Jurecic, Ph.D.
Associate Professor of Microbiology and Immunology, and Cell Biology and Anatomy
Description of Research
The research in Dr. Jurecic's laboratory focuses on the study of: (1) Molecular pathways that regulate self-renewal and differentiation of hematopoietic stem cells (HSCs) and cancer stem cells, (2) Functional heterogeneity and interconvertibility of HSCs, (3) Novel approaches to attenuate the progression of acquired immune-mediated Bone Marrow Failure (BMF) and Aplastic Anemia, (4) Acute and chronic effects of radiotherapy and chemotherapy on the hematopoietic system and HSCs, and pharmacological mitigation of early and late effects of radio and chemotherapy on HSC and immune system function, and (5) the role of E3 ubiquitin ligase RNF41 in development of Acute Promyelocytic Leukemia.
- Discovery of new E3 ubiquitin ligase that affects proliferation and differentiation of HSC and hematopoietic progenitors by regulating steady-state cytokine receptor levels through ligand-independent degradation, and that may be involved in etiology of hematological malignancies such as Acute Promyelocytic Leukemia.
- Finding that Wnt5a gene negatively regulates B cell proliferation, and that inactivation of Wnt5a leads to development of myeloid leukemias and B cell lymphomas. Discovery of the deletion of the WNT5a gene and/or loss of WNT5a expression in human primary leukemias, demonstrating for the first time that WNT5a gene functions as a tumor suppressor (in collaboration with Dr. Steve Jones, University of Massachussetts Medical School).
- Delayed treatment of sublethally irradiated mice with Leukadherins, novel β2 integrin agonists with anti-inflammatory and immunosuppressive properties, results in a statistically significant (A) recovery of BM cellularity, hematopoiesis and HSC and progenitor cell compartments, and (B) improvement of long-term HSC function.
- Treatment with novel β2 integrin agonists is safely and significantly (1) reducing BM aplasia and the loss of HSCs and progenitors, (2) improving survival in the mouse model of severe Aplastic Anemia, and (3) converting severe AA into moderate chronic and survivable disease.
- Utilizing the preclinical mouse model of chemotherapy treatment for breast cancer with influenza infection mouse model, Dr. Jurecic and his colleagues have shown that chemotherapy (a) causes long-lasting and significant reduction of HSCs and hematopoietic progenitors, (b) attenuates flu infection-induced emergency hematopoiesis necessary for rapid innate immune response to acute infections, and (c) significantly decreases the ability of virus-specific memory CD8 T cells to produce proinflammatory antiviral cytokines critical for efficient viral clearance.
Selected Cancer-Related Publications
Collaborating in the Multidisciplinary Research Program(s):