1990 M.D., College of Medicine
University of California, Irvine
1990 - 1993 Internal Medicine Residency
Mayo Graduate School of Medicine
1993 – 1996 Oncology Fellowship,
University of Washington Medical Center
Dr. Fero specializes in the use of hematopoietic stem cell transplantation for the treatment of hematological malignancies. This includes harvesting marrow or peripheral blood stem cells from normal donors for allogeneic transplants; or from patients undergoing autologous transplantation. His clinical activitivies range from the inpatient and outpatient care of patients actively undergoing allogeneic and autologous transplantation, and in the long term follow up of transplant recipients.
Mechanisms of Tumor Suppression by p27
Our lab has studied the cellular and physiological roles of cell cycle inhibitor proteins by studying mouse models with mutations of these genes. This includes the p27Kip1 (Cdkn1b) cdk inhibitor gene, and other inhibitors of the cyclin D pathway including p21, and Rb family members. Deletion of p27 in knockout mice has demonstrated that this protein ordinarily limits the overall size of adult animals as well as particular tissues including the thymus, spleen and intermediate lobe of the pituitary. Interestingly, p27 and other cell cycle inhibitors are also crucial for maintaining cellular quiescence in sensory tissues such as the cochlea and retina. We are interested in the role of these cell cycle inhibitors in cancer, which is characterized by clonal hyper-proliferation. On the flip-side we are also interested in the requirement of Cdk inhibitor proteins to maintain normal cellular quiescence and whether celluar regeneration can be augmented by removing their inhibitory activity. This included colloborative efforts with the Roberts, Clurman, Kemp labs here at the Center and auditory specialists at the University of Washington and across the globe. Key findings of this work has included:
We discovered that a highly conserved X-chromosomal gene, Xpcl1, is overexpressed in lymphomas arising in retroviral infected p27 knockout mice. This gene encodes a cluster of miRNA which we, and others, have shown are overexpressed upon targeting by retroviruses. Further work has shown that Xpcl1 is a potent oncogene, even in the absence of any additional oncogenic stimuli. However, Xpcl1 has mixed oncogenic and anti-oncogenic effects. One of the anti-oncogenic effects is the induction of p27 expression. This explains our observation that the combination of Xpcl1 overexpression and p27 deletion has dramatic synergy on lymphomagenesis. Since p27 is the primary inhibitor of cyclin D/Cdk4 activity in lymphocytes, we believe that these discoveries have important implications for the pathogenesis of human mantle cell lymphoma. This work has recently culminated in our recent submission research manuscript to Cancer Cell.
Gene expression in megakaryocyte progenitor populations and lineage specific reporters.
This is a multi-institutional collaborative project between Dr. Fero and colleagues at the FHCRC, the U.W. and Children’s Hospital in Philadelphia. Our intent is to characterize gene expression in hematopoietic progenitor cells, specifically in the megakaryocyte lineage, using mouse model systems. In addition we are developing a novel method to sequence the transcriptome of single cells. This would be a major breakthrough that finally permit researchers will allow us to discern the heterogeneity of gene expression in mixed cell populations. We will use this knowledge to develop new reporter systems to prospectively identify pure populations of megakaryocyte progenitors to facilitate our ability to produce platelets in the laboratory.