Matthew L. Fero
Appointments and Affiliations
The additional layers of regulation and functional redundancy of cell cycle proteins in mammals may reflect the need for alternative, tissue specific, growth control pathways. Mouse models have challanged our understanding the biochemical mechanisms of CDK regulation in mammals and have demonstrated both generalized and tissue specific patterns of cellular growth control. Targeted disruption of the CKI genes, p27Kip1, causes a hyperplastic syndrome with increased tumor susceptibility, and CDK activation.
A non-protein encoding RNA transcript, Xpcl1, is located on the X-chromosome and encodes a cluster of microRNAs. When activated these miRNA cause T-cell lymphomas through an unknown mechanism. We have shown that Xpcl1 expression and cell cycle activation are highly synergistic with respect to tumor development. We are working to understand the mechanism of action of the Xpcl1 miRNA and whether they may be used as novel diagnostic or therapeutic targets.
Although hematopoiesis is one of the best characterized cellular developmental pathways our understanding key regulators is lacking as evidenced by our limited ability to faithfully grow blood cells in the laboratory and our inability to purify homogeneous progenitor populations. We have initiated a project to address these constraints by characterizing transcriptiome variation of individual hematopoietic progenitor populations with second generation RNA-Seq technology, and the development of novel gene expression reporters.
Future ResearchThe Fero lab is highly interactive and has collaborative interactions with local and international groups. Our current research projects include the following:
- Mechanism of tumor suppression by the p27Kip1 CDK inhibitor
- Role of the Xpcl1 microRNA cluster in T-cell development
- Single cell transcriptome heterogeneity in hematopoiesis
- Novel gene mutations in leukemia and lymphoma
Honors and Awards
Board Certification and Eligibility
Current License(s) to Practice
- NIH/NHLBI: Controlling Hematopoietic Lineage Commitment from ESC to platelets, Co-Investigator (P.I.: Torok-Storb, B.), 9/30/2009 - 8/31/2016.
- NIH/NIDDK: Core Center of Excellence in Hematology, Sub-Project: Core E, Project Leader (P.I.: Torok-Storb, B.), 9/30/2010-06/30/2015.