Nancy Andrews

Positions:

Nanaline H. Duke Distinguished Professor of Pediatrics

Pediatrics
School of Medicine

Dean Emerita of the School of Medicine

School of Medicine
School of Medicine

Professor of Pediatrics

Pediatrics
School of Medicine

Professor of Pharmacology & Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1980

Yale University

M.S. 1980

Yale University

Ph.D. 1985

Massachusetts Institute of Technology

M.D. 1987

Harvard University

Grants:

Bridging the Gap to Enhance Clinical Research Program (BIGGER)

Administered By
Medicine, Infectious Diseases
Awarded By
National Institutes of Health
Role
Advisor
Start Date
End Date

School of Medicine 2017 Biddle

Administered By
School of Medicine
Awarded By
Mary Duke Biddle Foundation
Role
Principal Investigator
Start Date
End Date

Expansion of Animal Resources for Large Animals (Vivarium Expansion project)

Administered By
School of Medicine
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Genes that modify Iron loading in mice

Administered By
Pharmacology & Cancer Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Identification of Novel Genes That Modulate Systemic Iron Homeostasis

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Mentor
Start Date
End Date

Publications:

Disrupted iron homeostasis causes dopaminergic neurodegeneration in mice.

Disrupted brain iron homeostasis is a common feature of neurodegenerative disease. To begin to understand how neuronal iron handling might be involved, we focused on dopaminergic neurons and asked how inactivation of transport proteins affected iron homeostasis in vivo in mice. Loss of the cellular iron exporter, ferroportin, had no apparent consequences. However, loss of transferrin receptor 1, involved in iron uptake, caused neuronal iron deficiency, age-progressive degeneration of a subset of dopaminergic neurons, and motor deficits. There was gradual depletion of dopaminergic projections in the striatum followed by death of dopaminergic neurons in the substantia nigra. Damaged mitochondria accumulated, and gene expression signatures indicated attempted axonal regeneration, a metabolic switch to glycolysis, oxidative stress, and the unfolded protein response. We demonstrate that loss of transferrin receptor 1, but not loss of ferroportin, can cause neurodegeneration in a subset of dopaminergic neurons in mice.
Authors
Matak, P; Matak, A; Moustafa, S; Aryal, DK; Benner, EJ; Wetsel, W; Andrews, NC
MLA Citation
Matak, Pavle, et al. “Disrupted iron homeostasis causes dopaminergic neurodegeneration in mice.Proc Natl Acad Sci U S A, vol. 113, no. 13, Mar. 2016, pp. 3428–35. Pubmed, doi:10.1073/pnas.1519473113.
URI
https://scholars.duke.edu/individual/pub1123173
PMID
26929359
Source
pubmed
Published In
Proc Natl Acad Sci U S A
Volume
113
Published Date
Start Page
3428
End Page
3435
DOI
10.1073/pnas.1519473113

The channel kinase, TRPM7, is required for early embryonic development.

Global disruption of transient receptor potential-melastatin-like 7 (Trpm7) in mice results in embryonic lethality before embryonic day 7. Using tamoxifen-inducible disruption of Trpm7 and multiple Cre recombinase lines, we show that Trpm7 deletion before and during organogenesis results in severe tissue-specific developmental defects. We find that Trpm7 is essential for kidney development from metanephric mesenchyme but not ureteric bud. Disruption of neural crest Trpm7 at early stages results in loss of pigment cells and dorsal root ganglion neurons. In contrast, late disruption of brain-specific Trpm7 after embryonic day 10.5 does not alter normal brain development. We developed induced pluripotent stem cells and neural stem (NS) cells in which Trpm7 disruption could be induced. Trpm7(-/-) NS cells retained the capacities of self-renewal and differentiation into neurons and astrocytes. During in vitro differentiation of induced pluripotent stem cells to NS cells, Trpm7 disruption prevents the formation of the NS cell monolayer. The in vivo and in vitro results demonstrate a temporal requirement for the Trpm7 channel kinase during embryogenesis.
Authors
Jin, J; Wu, L-J; Jun, J; Cheng, X; Xu, H; Andrews, NC; Clapham, DE
MLA Citation
Jin, Jie, et al. “The channel kinase, TRPM7, is required for early embryonic development.Proc Natl Acad Sci U S A, vol. 109, no. 5, Jan. 2012, pp. E225–33. Pubmed, doi:10.1073/pnas.1120033109.
URI
https://scholars.duke.edu/individual/pub757602
PMID
22203997
Source
pubmed
Published In
Proc Natl Acad Sci U S A
Volume
109
Published Date
Start Page
E225
End Page
E233
DOI
10.1073/pnas.1120033109

TRP channel regulates EGFR signaling in hair morphogenesis and skin barrier formation.

A plethora of growth factors regulate keratinocyte proliferation and differentiation that control hair morphogenesis and skin barrier formation. Wavy hair phenotypes in mice result from naturally occurring loss-of-function mutations in the genes for TGF-alpha and EGFR. Conversely, excessive activities of TGF-alpha/EGFR result in hairless phenotypes and skin cancers. Unexpectedly, we found that mice lacking the Trpv3 gene also exhibit wavy hair coat and curly whiskers. Here we show that keratinocyte TRPV3, a member of the transient receptor potential (TRP) family of Ca(2+)-permeant channels, forms a signaling complex with TGF-alpha/EGFR. Activation of EGFR leads to increased TRPV3 channel activity, which in turn stimulates TGF-alpha release. TRPV3 is also required for the formation of the skin barrier by regulating the activities of transglutaminases, a family of Ca(2+)-dependent crosslinking enzymes essential for keratinocyte cornification. Our results show that a TRP channel plays a role in regulating growth factor signaling by direct complex formation.
Authors
Cheng, X; Jin, J; Hu, L; Shen, D; Dong, X-P; Samie, MA; Knoff, J; Eisinger, B; Liu, M-L; Huang, SM; Caterina, MJ; Dempsey, P; Michael, LE; Dlugosz, AA; Andrews, NC; Clapham, DE; Xu, H
MLA Citation
Cheng, Xiping, et al. “TRP channel regulates EGFR signaling in hair morphogenesis and skin barrier formation.Cell, vol. 141, no. 2, Apr. 2010, pp. 331–43. Pubmed, doi:10.1016/j.cell.2010.03.013.
URI
https://scholars.duke.edu/individual/pub757612
PMID
20403327
Source
pubmed
Published In
Cell
Volume
141
Published Date
Start Page
331
End Page
343
DOI
10.1016/j.cell.2010.03.013

Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA).

Iron deficiency is usually attributed to chronic blood loss or inadequate dietary intake. Here, we show that iron deficiency anemia refractory to oral iron therapy can be caused by germline mutations in TMPRSS6, which encodes a type II transmembrane serine protease produced by the liver that regulates the expression of the systemic iron regulatory hormone hepcidin. These findings demonstrate that TMPRSS6 is essential for normal systemic iron homeostasis in humans.
Authors
Finberg, KE; Heeney, MM; Campagna, DR; Aydinok, Y; Pearson, HA; Hartman, KR; Mayo, MM; Samuel, SM; Strouse, JJ; Markianos, K; Andrews, NC; Fleming, MD
MLA Citation
Finberg, Karin E., et al. “Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA).Nat Genet, vol. 40, no. 5, May 2008, pp. 569–71. Pubmed, doi:10.1038/ng.130.
URI
https://scholars.duke.edu/individual/pub757626
PMID
18408718
Source
pubmed
Published In
Nat Genet
Volume
40
Published Date
Start Page
569
End Page
571
DOI
10.1038/ng.130

Interleukin-6 induces hepcidin expression through STAT3.

Iron homeostasis is maintained through meticulous regulation of circulating hepcidin levels. Hepcidin levels that are inappropriately low or high result in iron overload or iron deficiency, respectively. Although hypoxia, erythroid demand, iron, and inflammation are all known to influence hepcidin expression, the mechanisms responsible are not well defined. In this report we show that the inflammatory cytokine interleukin-6 (IL-6) directly regulates hepcidin through induction and subsequent promoter binding of signal transducer and activator of transcription 3 (STAT3). STAT3 is necessary and sufficient for the IL-6 responsiveness of the hepcidin promoter. Our findings provide a mechanism by which hepcidin can be regulated by inflammation or, in the absence of inflammatory stimuli, by alternative mechanisms leading to STAT3 activation.
Authors
Wrighting, DM; Andrews, NC
MLA Citation
Wrighting, Diedra M., and Nancy C. Andrews. “Interleukin-6 induces hepcidin expression through STAT3.Blood, vol. 108, no. 9, Nov. 2006, pp. 3204–09. Pubmed, doi:10.1182/blood-2006-06-027631.
URI
https://scholars.duke.edu/individual/pub757640
PMID
16835372
Source
pubmed
Published In
Blood
Volume
108
Published Date
Start Page
3204
End Page
3209
DOI
10.1182/blood-2006-06-027631