Dr. Matthew L. Fero

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Fred Hutchinson Cancer Research Center
Clinical Research Division
Associate MemberAppointed: 2000
University of Washington
School of Medicine
Medicine
Oncology
Associate ProfessorAppointed: 2000
Professional Headshot of Matthew L. Fero

Mailing Address

Fred Hutchinson Cancer Research Center
1100 Fairview Avenue N.
Seattle, Washington 98109-1024
United States

Contact Information

Phone: (206) 667-5065
Fax: (206) 667-1494
mfero@fhcrc.org
http://labs.fhcrc.org/fero/

Qualifications

Diplomate, American Board of Internal Medicine, Medical Oncology, 1996.
Diplomate, American Board of Internal Medicine, Internal Medicine, 1993.
M.D., University of California, Irvine, 1990.
B.A., University of California, Berkeley, Microbiology, 1984.

Expertise and Research Interests

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.

Other Expertise

Clinical Expertise: Hematopoietic stem cell transplantation

Future Research

The 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

Keywords

COS Keywords:

Animal Models, Biochemistry, Cancer or Carcinogenesis, Cell Cycle, Clinical Research Or Studies, Hematology, Medical Genetics, Oncology.

Memberships

American Association for Cancer Research
American Society of Hematology
Puget Sound Oncology Consortium

Patents

Compositions and methods for mediating cell cycle progression, Patent Number: 5958769, 1999, Institution-owned, United States.

Publications

  • Vigorito AC, Campregher PV, Storer BE, Carpenter PA, Moravec CK, Kiem HP, Fero ML, Warren EH, Lee SJ, Appelbaum FR, Martin PJ, Flowers ME (Jul 2009) Evaluation of NIH consensus criteria for classification of late acute and chronic GVHD., Blood, 114 (3), 702-8 Abstract
  • Glover CE, Gurley KE, Kim KH, Storer B, Fero ML, Kemp CJ (Jun 2009) Endocrine dysfunction in p27Kip1 deficient mice and susceptibility to Wnt-1 driven breast cancer., Carcinogenesis, 30 (6), 1058-63 Abstract
  • Flowers ME, Storer B, Carpenter P, Rezvani AR, Vigorito AC, Campregher PV, Moravec C, Kiem HP, Fero M, Georges G, Warren E, Lee S, Sanders JE, Appelbaum F, Martin PJ (Dec 2008) Treatment change as a predictor of outcome among patients with classic chronic graft-versus-host disease., Biology of Blood and Marrow Transplantation, 14 (12), 1380-4 Abstract
  • Garrett-Engele CM, Tasch MA, Hwang HC, Fero ML, Perlmutter RM, Clurman BE, Roberts JM (Dec 2007) A mechanism misregulating p27 in tumors discovered in a functional genomic screen., PLoS Genetics, 3 (12), e219 Abstract
  • Chien WM, Garrison K, Caufield E, Orthel J, Dill J, Fero ML (Mar 2007) Differential gene expression of p27Kip1 and Rb knockout pituitary tumors associated with altered growth and angiogenesis., Cell Cycle, 6 (6), 750-7 Abstract
  • Chien WM, Rabin S, Macias E, Miliani de Marval PL, Garrison K, Orthel J, Rodriguez-Puebla M, Fero ML (Mar 2006) Genetic mosaics reveal both cell-autonomous and cell-nonautonomous function of murine p27Kip1., Proceedings of the National Academy of Sciences of the United States of America, 103 (11), 4122-7 Abstract
  • Walkley CR, Fero ML, Chien WM, Purton LE, McArthur GA (Feb 2005) Negative cell-cycle regulators cooperatively control self-renewal and differentiation of haematopoietic stem cells., Nature Cell biology, 7 (2), 172-8 Abstract
  • Hwang HC, Martins CP, Bronkhorst Y, Randel E, Berns A, Fero M, Clurman BE, Identification of oncogenes collaborating with p27Kip1 loss by insertional mutagenesis and high-throughput insertion site analysis, Proceedings of the National Academy of Sciences (USA), 99(17), 11293-8, Aug 2002 Abstract
  • McArthur GA, Foley KP, Fero ML, Walkley CR, Deans AJ, Roberts JM, Eisenman RN, MAD1 and p27(KIP1) cooperate to promote terminal differentiation of granulocytes and to inhibit Myc expression and cyclin E-CDK2 activity, Molecular and Cellular Biology, 22(9), 3014-23, May 2002 Abstract
  • Fero ML, Kemp CJ (2002) p27 (Kip1), The Encyclopedia of Molecular Medicine., New York, John Wiley & Sons, Inc., 2363-6 pages (bookchapter)
  • Beier R, Burgin A, Kiermaier A, Fero M, Karsunky H, Saffrich R, Moroy T, Ansorge W, Roberts J, Eilers M, Induction of cyclin E-cdk2 kinase activity, E2F-dependent transcription and cell growth by Myc are genetically separable events, The Embo Journal, 19(21), 5813-23, November 2000 Abstract
  • Levine EM, Close J, Fero M, Ostrovsky A, Reh TA, p27(Kip1) regulates cell cycle withdrawal of late multipotent progenitor cells in the mammalian retina, Developmental Biology, 219(2), 299-314, 2000 Abstract
  • Lowenheim H, Furness DN, Kil J, Zinn C, Gultig K, Fero ML, Frost D, Gummer AW, Roberts JM, Rubel EW, Hackney CM, Zenner HP, Gene disruption of p27(Kip1) allows cell proliferation in the postnatal and adult organ of corti, Proceedings of the National Academy of Sciences (USA), 96(7), 4084-8, 1999 Abstract
  • Hiromura K, Pippin JW, Fero ML, Roberts JM, Shankland SJ, Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27(Kip1), Journal of Clinical Investigation, 103(5), 597-604, March 1999 Abstract
  • Coats S, Whyte P, Fero ML, Lacy S, Chung G, Randel E, Firpo E, Roberts JM, A new pathway for mitogen-dependent cdk2 regulation uncovered in p27(Kip1)-deficient cells, Current Biology, 9(4), 163-73, 1999 Abstract
  • Fero ML, Randel E, Gurley KE, Roberts JM, Kemp CJ, The murine gene p27Kip1 is haplo-insufficient for tumour suppression, Nature, 396(6707), 177-80, 1998 Abstract
  • Ophascharoensuk V, Fero ML, Hughes J, Roberts JM, Shankland SJ, The cyclin-dependent kinase inhibitor p27Kip1 safeguards against inflammatory injury, Nature Medicine, 4(5), 575-80, May 1998 Abstract
  • Durand B, Fero ML, Roberts JM, Raff MC, p27Kip1 alters the response of cells to mitogen and is part of a cell-intrinsic timer that arrests the cell cycle and initiates differentiation, Current Biology, 8(8), 431-40, 1998 Abstract
  • Fero ML, Rivkin M, Tasch M, Porter P, Carow CE, Firpo E, Polyak K, Tsai LH, Broudy V, Perlmutter RM, Kaushansky K, Roberts JM, A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice, Cell, 85(5), 733-44, May 1996 Abstract
  • Morgan WF, Fero ML, Land MC, Winegar RA, Inducible expression and cytogenetic effects of the EcoRI restriction endonuclease in Chinese hamster ovary cells, Molecular and Cellular Biology, 8(10), 4204-11, October 1988 Abstract
  • Morgan WF, Bodycote J, Doida Y, Fero ML, Hahn P, Kapp LN, Spontaneous and 3-aminobenzamide-induced sister-chromatid exchange frequencies estimated by ring chromosome analysis [published erratum appears in Mutagenesis 1988 May, Mutagenesis, 1(6), 453-9, November 1986 Abstract
  • Morgan WF, Bodycote J, Fero ML, Hahn PJ, Kapp LN, Pantelias GE, Painter RB, A cytogenetic investigation of DNA rereplication after hydroxyurea treatment: implications for gene amplification, Chromosoma, 93(3), 191-6, 1986 Abstract

Profile Details

Last Verified: 8/4/2009

COS Expertise ID #872746
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