Nancy A. Speck
University of Pennsylvania
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Primary Section: 41, Medical Genetics, Hematology, and Oncology Membership Type:
Member
(elected 2019)
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Biosketch
Nancy Speck is a hematologist recognized for her work on transcription factors called core-binding factors (RUNX1 and CBFβ), including their role in hematopoietic stem cell formation in the embryo, and how mutations in RUNX1 and CBFB contribute to leukemia. Speck was born in Jersey City, New Jersey and grew up in Timonium, Maryland. She graduated from Western Maryland College (now McDaniel College) in 1977 with dual majors in biology and chemistry, and with a Ph.D. in biochemistry from Northwestern University in 1983 where she studied immunology. She was a postdoctoral fellow at the Whitehead Institute and Center for Cancer Research at the Massachusetts Institute of Technology. She joined the faculty of Dartmouth Medical School in 1989, and moved to the University of Pennsylvania in 2008, where she is currently a Professor and Chair of the Department of Cell and Developmental Biology in the Perelman School of Medicine.
Research Interests
Nancy Speck determined that the disease specificity of a mouse retrovirus was most strongly influenced by a single transcription factor-binding site named “core.” She purified a core-binding factor (CBF) from calf thymus, cloned the genes encoding its subunits, and showed that CBF consists of DNA-binding (RUNX1) and non-DNA binding (CBFβ) subunits. The genes encoding RUNX1 and CBFβ were contemporaneously cloned by other laboratories from the breakpoints of the t(8;21) and inv(16) in acute myelogenous leukemia; Speck’s biochemical studies established that the genes disrupted on chromosomes 21 and 16 encoded two subunits of a single transcription factor.
Speck determined that RUNX1 and CBFβ were obligate partners in vivo, and were required for the formation of definitive blood cells, including hematopoietic stem cells, in the embryo. She discovered that RUNX1 expression marks a small population of endothelial cells in the embryo called "hemogenic endothelium,” and that blood cell formation from hemogenic endothelium was absolutely dependent on RUNX1. The existence of hemogenic endothelium was not widely accepted at that time; Speck’s identification of a transcription factor specifically expressed in hemogenic endothelium, and required for blood cell formation from hemogenic endothelium, were important for establishing this concept. Her current research focuses on hematopoietic stem cell formation in the embryo, and how inherited mutations in RUNX1 predispose individuals to leukemia.
