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Appointments:
Assistant Professor
Ben May Department for Cancer Research
Committee Cancer Biology
Committee on Immunology
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Education:
Ph.D. The Beatson Institute for Cancer
Research, 1990
B.Sc., University of Edinburgh, 1986
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Contact:
Phone: (773) 834-8309
Fax:
(773) 702-6260
E-Mail: kmacleod@huggins.bsd.uchicago.edu
Address:
The University of Chicago
GCIS W338
929 East 57th Street
Chicago, Illinois 60637
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Related Research Interests:
Apoptosis
Cell Cycle
Cell
Differentiation/Development
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Kay Macleod, Ph.D.
Regulation of Cell Cycle Checkpoints and Cell Death by
the RB Tumor Suppressor in Response to Oxidative Stress and DNA Damage
Research Summary
Our work investigates the critical role played by the RB tumor
suppressor (and its target genes) in sensing and managing the response
to oxidative stress and DNA damage, through modulation of cell death
regulators and induction of cell cycle checkpoints.
Our investigations make use of three biological systems: (1) the blood
system in which we investigate the role of pRb and its downstream E2f
targets in stress responses during differentiation; (2) the mammary
gland in which we are exploring how non-apoptotic cell death regulates
mammary epithelial development and determines the rate of tumor
progression and metastasis; and, (3) the liver, in which we investigate
the role of non-apoptotic cell death and regenerative proliferation in
hepatocyte function, liver disease and cancer. For example, using mouse
models, we are currently examining how anti-oxidants might be used to
prevent myelodysplasia and progression to myeloid leukemia. We are also
examining how stress-induced autophagy prevents necrosis and tumor
progression in a mouse model of breast cancer. Furthermore, we have
identified a role for key RB/E2F target genes in preventing oxidative
damage in hepatocytes and our current work is exploiting genetically
engineered mouse strains and real-time imaging in vivo to determine the
role of these genes in cancer progression. In summary, we are
exploiting our findings regarding basic developmental processes and
stress responses in biology to address mechanisms of tumor progression
and drug action in cancer.
Selected Papers
Spike, BT, Dirlam, A, Dibling, BC, Marvin, J, Williams, BO, Jacks, T
& KF Macleod The Rb tumor suppressor is required for stress
erythropoiesis. The EMBO Journal. 23: 4319-29 (2004).
Liu, H., Dibling, B., Spike B, Dirlam, A & Macleod, K: Novel
functions of the RB tumor suppressor. Curr. Op. Gen. & Dev. 14,
55-64 (2004).
Liu H, Thompson AM & KF Macleod: A novel form of pRb expressed
during normal myelopoiesis and in tumor associated macrophages. Cell
Proliferation 38: 13-24 (2005).
Spike, BT & KF Macleod The Rb tumor suppressor in stress responses
and hematopoietic homeostasis. Cell Cycle 4: e181-184 (2005).
Dirlam A.
& KF Macleod :The Retinoblastoma tumour suppressor. The Cancer Handbook. 2nd
Edition. Chapter 24. Edited by Malcolm R Alison. John Wiley & Sons
Ltd.
(2006).
Kristin Tracy, Benjamin C. Dibling, Benjamin T. Spike, James Knabb,
Paul Schumacker & Macleod KF: BNIP3 is an RB/E2F target gene
required for hypoxia-induced autophagy. Mol. Cell Biol. 27, 6229-42
(2007).
Spike, BT, Dibling BC & Macleod, KF: Hypoxic stress underlies
defects in erythroblast islands in the Rb null mouse. Blood 110,
2173-81 (2007).
Abhinav Diwan, Andrew G Koesters, Amy M Odley, Suvarnamala Pushkaran,
Christopher P Baines, Benjamin T Spike, Diedre Daria, Anil G Jegga,
Hartmut Geiger, Bruce J Aronow, Jeffrey D Molkentin, Kay F Macleod,
Theodosia A Kalfa, Gerald W Dorn II: Unrestrained erythroblast
development in Nix-/- mice reveals a mechanism for apoptotic modulation
of erythropoiesis. Proc.Natl.Acad.Sci. USA 104, 6794-9 (2007).
Dirlam, A. Spike, B.T. & Macleod, KF: De-regulated E2f-2 activity
drives deregulated cell cycle and maturation defects in Rb null
erythroblasts. In press at Mol.Cell Biol. (2007).
Benjamin T Spike & Kay F. Macleod: Effects of hypoxia on
heterotypic interactions with macrophages. In press at Cell Cycle 6,
(21) (2007).
Kristin Tracy & Kay F. Macleod: Regulation of mitochondrial
integrity, autophagy and cell survival by BNIP3. In press at
Autophagy 3, (6) (2007).
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Faculty and Research
Programs
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