Nancy Speck
University of Pennsylvania, PA·Biology
Every blood cell in the body comes from hematopoietic stem cells (HSCs), which first form in the embryo from a small group of blood-vessel lining cells called hemogenic endothelium. How this transition is controlled matters for two practical reasons.
- Fields
Biology
Genetics
Microbiology & Immunology
- Topics
hematopoietic stem cells
pre-HSCs
hematopoiesis
- Grants
- 3 known grants, through May 2030
What they work on
- Determine which components of the TGFβ/BMP signaling pathways must be inhibited, and at what time, to improve maturation of SMAD7-deficient pre-HSCs into HSCs, using a quantitative ex vivo culture system with mouse embryo cells.
- Track the molecular changes as pre-HSCs mature into HSCs using clonal barcoding single-cell RNA sequencing, then apply these insights to optimize generation of HSCs from induced pluripotent stem cells.
- Determine how the transcription factor RUNX1 restrains background type I interferon signaling in granulocyte-monocyte progenitors, and whether this signaling causes increased retroelement accessibility in RUNX1-mutant cells.
- Test whether elevated inflammation in RUNX1 mutant mice strengthens innate immune training, the lasting heightened response of innate immune cells, after exposure to the TLR4 ligand lipopolysaccharide.
- Examine GMPs and neutrophils from patients with familial platelet disorder for an epigenomic activation signature, altered neutrophil subpopulations and hyper-responses to activating signals.
- Map transcriptionally active retroelements in hemogenic endothelial cells to exact genome locations using long-read sequencing and retroelement-adapted bioinformatics, and test whether they activate genes for blood stem cell formation.
- Test whether RUNX1 regulates the activity of retrotransposon long terminal repeats that carry RUNX1 binding motifs during formation of hematopoietic stem and progenitor cells in the embryo.
More about the research
Labs still struggle to make fully working HSCs from stem cells for transplantation. And when blood-forming genes go wrong, the result can be inflammation and leukemia. The grants cover three questions: what signals help immature 'pre-HSCs' finish becoming true HSCs, how repetitive retroelement DNA helps switch on the blood-forming program, and how mutations in RUNX1, a key blood-development transcription factor, inflame the innate immune system.
Why it matters
Finding the signals that let pre-HSCs mature could improve protocols for generating hematopoietic stem cells from human iPSCs for transplantation. Understanding how inherited RUNX1 mutations amplify inflammation may eventually guide efforts to reduce inflammation, and possibly leukemia risk, in people with familial platelet disorder with predisposition for myeloid malignancy. The retroelement work adds basic understanding of how so-called 'junk DNA' helps control blood formation in the embryo.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Strategies to promote the maturation of pre-hematopoietic stem cells (pre-HSCs) into HSCs
NIH · Aug 2026 – May 2030
Regulation of inflammation in myeloid progenitors and neutrophils by RUNX1
NIH · May 2026 – Jan 2030
Retroelement-mediated cis-regulation of embryonic hematopoiesis
NIH · Aug 2025 – Jul 2027
Closest labs
Pamela Wenzel
University of Texas Health Science Center at Houston, TX·Biology
Test how interrupting mitochondrial maturation affects commitment of hemogenic endothelium (blood-forming vessel cells) to blood fate, using drugs, in vitro vessel-mimicking platforms and cardiac mutant mice.
Christopher Michael Sturgeon
Icahn School of Medicine at Mount Sinai, NY·Biology
Define the signaling, transcriptional and epigenetic mechanisms that specify each hemogenic mesoderm subset and restrict it to one blood program, aiming to improve in vitro production of progenitors including hematopoietic stem cells.
Waihay Wong
Northwestern University, IL·Medicine & Clinical Research·Early-career
Test whether the NLRP3 inflammasome, an immune-cell sensor that triggers inflammatory signaling, is required for Tet2-deficient blood cells to outcompete normal ones, using mouse models of clonal hematopoiesis, human cell xenografts and patient specimens.
The school
University of Pennsylvania: 90 labs on PI Pages, $2.2B a year on research, 750 research doctorates a year.
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