Marshall S. Horwitz
Professor of Medicine
Adjunct Professor of Genome Sciences and of Pathology

Dr. Horwitz's research interests are focused on cancers of the blood and bone marrow failure syndromes. His laboratory employs genetic linkage analysis and positional candidate cloning approaches to map and identify genes responsible for familial predisposition to leukemia, lymphoma, and bone marrow failure syndromes. His laboratory has found genes responsible for human cyclic neutropenia, canine cyclic hematopoiesis, and severe congenital neutropenia (Kostmann syndrome). The lab employs molecular biology and biochemical approaches aimed at elucidating mechanisms of cellular differentiation during hematopoiesis. More recently, his laboratory has embarked on a new approach for constructing cell fate maps by inferring the order in which somatic mutations accumulate during the course of development.

Publications:

Horwitz, M., Benson, K.F., Person, R., Aprikyan, A.G., and Dale, D.C.
(1999) Mutations in ELA2, encoding neutrophil elastase, define a 21-day
biological clock in cyclic haematopoiesis. Nature Genetics 23:433-436.

Person, R.E., Li, F.-Q., Duan, Z., Benson, K.F., Papadaki, H.A.,
Eliopoulos, G., Kaufman, C., Bertolone, S.J., Nakamato, B.,
Papayannopoulou, T., Grimes, H.L., and Horwitz, M. (2003) Gfi1
proto-oncogene mutations cause human neutropenia and targets neutrophil
elastase. Nature Genetics 34:308-312.

Benson, K.F., Li, F.-Q., Person, R.E., Albani, D., Duan, Z., Wechsler,
J., Meade-White, K., Williams, K., Acland, G.M., Niemeyer, G., Lothrop,
C.D., and Horwitz, M. (2003) Mutations associated with neutropenia in
dogs and humans disrupt intracellular transport of neutrophil elastase.
Nature Genetics 35:90-96.

Duan, Z., Zarebski, A., Montoya-Durango, D., Grimes, H.L., and Horwitz,
M. (2005) Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by
recruitment of histone lysine methyltransferase G9a and histone
deacetylase HDAC1. Molecular and Cellular Biology 25:10338-10351.

Salipante, S.J., and Horwitz, M.S. (2006) Phylogenetic fate mapping.
Proceedings National Academy of Sciences USA 103:5448-5453.51.

Duan, Z.J., Person, R.E., Lee, H.-H., Huang, S., Donadieu, J., Badolato,
R., Grimes, H.L., Papayannopoulou, T., and Horwitz, M.S. (2007)
Epigenetic regulation of protein-coding and microRNA genes during
myelopoiesis by the Gfi1-interacting, tumor suppressor PRDM5. Molecular
and Cellular Biology 27:6889-6902.

Salipante, S.J., Thompson, J.M., and Horwitz, M.S. Phylogenetic fate
mapping: Theoretical and experimental studies applied to the development
of mouse fibroblasts. Genetics (accepted).

Zarebski, A., Velu, C.S., Baktula, A.M., Bourdeau, T., Horman, S.R.,
Basu, S., Horwitz, M.S., Hildeman, D., Trent, J.O., and Grimes, H.L. The
human severe congenital neutropenia-associated Gfi1 N382S mutant blocks
murine granulopoiesis through CSF1. Immunity (accepted).

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