Growing lab of a junior faculty member seeks talented postdoctoral fellow. Bone marrow suppression and pancytopenia can result from chronic inflammation. Bone marrow suppression is a risk factor for increased mortality for patients with chronic infections and aplastic anemia. However, very little is known about the mechanisms by which inflammatory cytokines affect the hematopoietic progenitors that reside in bone marrow. We discovered that interferon gamma (IFNγ) promotes hematopoietic stem cell (HSC) division and myeloid differentiation in a mouse model of Mycobacterium avium infection. While this response can be helpful in the short term, it may be deleterious over the long term, with prolonged inflammation leading to stem cell exhaustion. We have previously demonstrated that interferons, a class of inflammatory cytokines, directly activate hematopoietic stem cells (HSCs) to divide (Nature 2010). HSCs are the precursors of all cells of the peripheral blood, and they usually reside in a quiescent state in the bone marrow. Our work is among the first to demonstrate that inflammatory signaling can directly activate HSCs. Impaired quiescence mechanisms during long-term interferon stimulation result in differentiation and exhaustion of the HSC pool (Blood 2011, Stem Cells 2014, Cell Reports 2016). Meanwhile, basal inflammatory signaling mediated through the intestinal microbiome is required to maintain normal blood homeostasis (Blood, 2017). Ongoing work is focused on defining molecular pathways underlying these phenomena. This work will elucidate how inflammatory signals affect the pattern of HSC differentiation as well as how infections can contribute to aging and oncogenesis.
Our lab is located at Baylor College of Medicine, situated in the thriving Texas Medical Center in Houston, the most diverse city in the nation. We encourage women and minorities with a background in immunology, microbiology, or stem cell biology to apply. Current projects in the lab include: Mediators of interferon-dependent HSC proliferation and differentiation. We conducted transcriptional profiling of HSCs from naïve and infected animals to identify molecular mediators of the HSC immune response. Currently we are characterizing candidate genes from that screen for their role in HSC quiescence and differentiation. Investigating the effects of antibiotic treatment on primitive hematopoiesis. We are utilizing a mouse model of long-term antibiotic therapy to investigate how changes in microbiome and basal inflammatory tone affect hematopoiesis. Role of Dnmt3a in hematopoietic stem cell survival during infection. We are investigating how epigenetic regulation participates in stress hematopoiesis and whether this pathway can be used to select against preleukemic hematopoietic stem cell clones.
Matatall KA, Jeong M, Chen S, Sun D, Chen F, Mo Q, Kimmel M, and King KY. (2016) Chronic infection depletes hematopoietic stem cells through stress-induced terminal differentiation. Cell Reports. 17, 2584-95. PMID: 27926863.
Josefsdottir KS, Baldridge MT, Kadmon CS, and King KY. (2017) Antibiotics impair murine hematopoiesis by depleting intestinal microbiota. Blood. 129(6):729-739. PMID: 7879260.
Interested candidates should send a CV and cover letter to email@example.com.
Closing Date : 15-Mar-2017
Contact Person : Katrin Ottersbach
Contact Number : 0131 651 9511
Contact Email : firstname.lastname@example.org
Postdoctoral Fellow in Developmental Haematopoiesis and Infant Leukaemia MRC Centre for Regenerative Medicine & Edinburgh Cancer Research UK Centre The University of Edinburgh Applications are invited for a postdoctoral fellowship within the group of Dr Katrin Ottersbach, whose research centres on the developmental origins of haematopoiesis and infant leukaemia. The fellow will investigate the origin and pathogenesis of MLL-AF4-associated infant leukaemia, with a particular focus on the contribution of the foetal microenvironment. The MRC Centre for Regenerative Medicine provides a world-renowned environment designed to develop research careers of postdoctoral fellows and train them to become international leaders in stem cell and cancer biology.
The applicants must have a PhD in developmental biology, leukaemia or molecular biology/biochemistry and a minimum of 5 years’ research experience. The appointee should have experience in mouse models and multicolour flow cytometry, with additional experience in molecular biology techniques such as RNA-Seq and ATAC-Seq being highly desirable. Excellent communication and interpersonal skills and the ability to work as part of a team as well as semi-independently are crucial. This full-time post is available for 3 years in the first instance and available from 1 April 2017.