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About
Dr. Pamela Hoodless, PhD
Senior Scientist
- Associate Professor, Medical Genetics, University of British Columbia
- Faculty Member, Genome Science & Technology Graduate Program,
University of British Columbia
- Faculty Member, Developmental and Cell Biology, University of British
Columbia
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Associate Member, Bioinformatics Training Program, CIHR
Education:
B.Sc, Biochemistry, Queen's University, 1985
PhD, Biochemistry, Queen's University, 1991
Research Interest
My laboratory uses state of the art genomic
technologies to shed new light on classical processes in
developmental biology. We are exploring regulatory mechanisms in
heart and gastrointestinal tract development in the mouse embryo
using genome-wide analysis of gene expression, transcription factor
binding, and histone modifications. We have two main areas of focus:
Organogenesis in the
definitive endoderm
The control
of gene expression during liver differentiation
The liver is a fascinating organ which controls a
wide-array of homeostatic processes in the body including
detoxification, metabolism and bile production. Liver formation
initiates as a bud that evaginates from the foregut endoderm in
response to signals from the neighbouring cardiac mesoderm and the
septum transversum. This bud grows and differentiates to form the
functional liver.
We are interested in the
process of gene regulation during liver formation from the
endoderm through to the adult organ.
We are using
sequenced-based gene expression methods to analyze changes in
gene expression patterns throughout differentiation of
hepatocytes, the primary functional cell of the liver. We are
correlating gene expression changes with transcriptional
regulation by using chromatin immunoprecipiation coupled with
next generation sequencing (ChIP-seq) to examine the patterns of
transcription factor binding and histone modifications in the
embryonic hepatoblast and adult hepatocyte. Analysis of
microRNAs in this same process is also ongoing. Our work will
investigate the transcriptional networks and mechanisms that
function during hepatocyte differentiation.
Signaling pathways that control midgut
formation
The midgut is the region of the definitive
endoderm that will form part of the pancreas and the intestine. By
using gene expression analysis, we have identified a series of novel
genes that have distinct patterns of expression in the endoderm. One
of these genes, Nephrocan, is exclusively expressed in the midgut of
the early embryo. We are using this gene to explore the signaling
mechanisms controlling midgut formation in the mouse embryo.
Our work will provide insights into the origins
and functions of normal and cancer stem cells of the intestine and
liver. Moreover, there is growing interest in differentiating
pluripotent stem cells from many different sources in the laboratory to develop tissues for drug testing and transplantation.
Understanding the normal in
vivo differentiation processes will contribute to the
development of better methodologies for the differentiation of cells
in the laboratory for these purposes.
Heart valve formation
Congenital heart malformations are the most
common form of birth defects, with many of these involving the
heart valves.
In the embryonic heart, the valves develop in the
region between the atria and the ventricles, known as the
atrioventricular canal (AVC) and in the region where blood flows
into the major arteries, known as the outflow tract (OFT). Valve
formation initiates in these regions when cells of the
endocardium lining of the heart, undergo endothelial-to-mesenchymal
transition (EMT) and migrate into the region, known as the
endocardial cushion, located between the endocardium and the
myocardium. The cushions then undergo remodeling through
cellular differentiation to form the valve leaflets and these
cells secrete the extracellular matrix that provides the
mechanical flexibility to the valve leaflets.
Our work is focusing on the transcriptional
networks that control valve leaflet formation during the early
stages of valve formation. As with the liver, we are using cutting
edge gene expression analysis methodology and ChIP-seq to examine
functions of transcription factors and histone modifications in the
control of valve formation.
Of interest, valve calcification in adults has been linked to the
same pathways that control valve formation in the embryo. Our work
will provide insights into potential targets of congenital heart
defects as well as adult heart valve disease. In addition, our work
will contribute to a greater understanding of EMT, which is the
major driver of cancer metastases.
Publications
Chang AC, Fu Y, Garside VC, Niessen K, Chang
L, Fuller M, Setiadi A, Smrz J, Kyle A, Minchinton A, Marra M,
Hoodless PA, Karsan A. Notch Initiates the
Endothelial-to-Mesenchymal Transition in the Atrioventricular
Canal through Autocrine Activation of Soluble Guanylyl Cyclase.
Dev Cell 21(2): 288-300, 2011.
View
Abstract
Cullum R,
Alder O, Hoodless PA. The next generation: using new sequencing technologies
to analyze gene regulation. Respirology 16(2):210-222, 2010.
View
Abstract
Robertson G,
Schein J, Chiu R, Corbett R, Field M, Jackman SD, Mungall K, Lee
S, Okada HM, Qian JQ, Griffith M, Raymond A, Thiessen N, Cezard
T, Butterfield YS, Newsome R, Chan SK, She R, Varhol R, Kamoh B,
Prabhu AL, Tam A, Zhao Y, Moore RA, Hirst M, Marra MA, Jones SJ,
Hoodless PA, Birol I. De novo assembly and
analysis of RNA-seq data. Nat Methods 7(11): 909-912, 2010.
View
Abstract
Hoffman BG, Robertson G, Zavaglia PB, Beach M, Cullum R, Lee S,
Soukhatcheva G, Li L, Wederell ED, Thiessen N, Bilenky M, Cezard
T, Tam A, Kamoh B, Birol I, Dai D, Zhao YJ, Hirst M, Verchere B,
Helgason CD, Marra MA, Jones SJM, Hoodless PA.
Locus co-occupancy, nucleosome positioning, and
H3K4me1 regulate the functionality of FOXA2-, HNF4A-, and
PDX1-bound loci in islets and liver.
Genome Res 20(8): 1037-51, 2010.
View
Abstract
Hassan AS, Hou J, Wei W, Hoodless PA,
Expression of two novel transcripts in the mouse definitive endoderm.
Gene Expr Patterns 10:127-134, 2010.
View Abstract
McKnight K, Hou J,
Hoodless PA.
FoxH1 and FoxA2 are not required for formation of the midgut and
hindgut definitive endoderm.
Dev Biol 337: 471-481, 2010.
View Abstract
Vrljicak P, Chang AC, Morozova O,
Wederell ED, Niessen K, Marra MA, Karsan A, Hoodless PA. Genomic
Analysis Distinguishes Phases of Early Development of the Mouse
Atrio-Ventricular
Canal.
Physiol Genomics 40(3): 150-157, 2010.
View Abstract
Wederell ED, Bilenky M , Cullum R, Thiessen N, Dagpinar M, Delaney A,
Varhol R, Zhao YJ, Zeng T, Bernier B, Ingham M, Hirst M, Robertson G
Marra MA, Jones S, Hoodless PA.
Global Analysis of In Vivo
FoxA2 Binding Sites in Mouse Adult Liver Using Massively Parallel
Sequencing. Nuc Acids Res 36:
4549-4564, 2008.
View Abstract
Robertson AG, Bilenky M, Tam A, Zhao Y, Zeng T, Thiessen N, Cezard T,
Fejes A, Wederell E, Cullum R, Euskirchen G, Krzywinski M, Birol I,
Snyder M, Hoodless PA, Hirst
M, Marra MA, Jones SJM.
Genome wide relationship between histone H3 lysine 4 mono-and-tri
methylation and transcription factor binding.
Genome Res 18:1906-1917, 2008
View Abstract
Niessen K, Fu YX, Chang L, Wong F, McFadden D,
Hoodless PA & Karsan A.
Slug is a direct Notch target required for initiation of cardiac cushion
cellularization.
J
Cell Biol
182:315-25, 2008.
View Abstract
Hoffman
BG, Zavaglia B, Witzsche J, Ruiz de Algara T, Beach M, Hoodless PA,
Jones SJ, Marra MA, & Helgason CD. Identification of transcripts with
enriched expression in the developing and adult pancreas. Genome Biol 9
(6): R99, 2008.
View Article
Bowie
MB,
Kent
DG, Dykstra B, McKnight KD, McCaffrey L, Hoodless PA, & Eaves CJ.
Identification of a new intrinsically timed developmental checkpoint
that reprograms key hematopoietic stem cell properties. Proc Natl Acad
Sci U S A 104 (14): 5878-82, 2007.
View Abstract
Hou J, Charters AM,
Lee SC, Zhao Y, Wu MK, Jones SJ, Marra MA, & Hoodless PA. A systematic
screen for genes expressed in definitive endoderm by Serial Analysis of
Gene Expression (SAGE). BMC Dev Biol 7: 92, 2007.
View Abstract
Khattra J, Delaney
AD, Zhao Y, Siddiqui A, Asano J, McDonald H, Pandoh P, Dhalla N, Prabhu
AL, Ma K, Lee S, Ally A, Tam A, Sa D, Rogers S, Charest D, Stott J,
Zuyderduyn S, Varhol R, Eaves C, Jones S, Holt R, Hirst M, Hoodless PA,
& Marra MA. Large-scale production of SAGE libraries from microdissected
tissues, flow-sorted cells, and cell lines. Genome Res 17 (1): 108-16,
2007.
View Abstract
McKnight KD, Hou J, &
Hoodless PA. Dynamic expression of thyrotropin-releasing hormone in the
mouse definitive endoderm. Dev Dyn 236 (10): 2909-17, 2007.
View Abstract
Noorali S, Kurita T,
Woolcock B, de Algara TR, Lo M, Paralkar V, Hoodless P, & Vielkind J.
Dynamics of expression of growth differentiation factor 15 in normal and
PIN development in the mouse. Differentiation 75 (4): 325-36, 2007.
View Abstract
Bowie MB,
McKnight KD, Kent DG, McCaffrey L, Hoodless PA, & Eaves CJ.
Hematopoietic stem cells proliferate until after birth and show a
reversible phase-specific engraftment defect. J Clin Invest 116 (10):
2808-16, 2006.
View Abstract
Houde C, Dickinson
RJ, Houtzager VM, Cullum R, Montpetit R, Metzler M, Simpson EM, Roy S,
Hayden MR, Hoodless PA, & Nicholson DW. Hippi is essential for node
cilia assembly and Sonic hedgehog signaling. Dev Biol 300 (2): 523-33,
2006.
View Abstract
Mar L, &
Hoodless PA.
Embryonic fibroblasts from mice lacking Tgif were defective in
cell cycling. Mol Cell Biol 26
(11): 4302-10, 2006.
View Abstract
Siddiqui AS, Khattra
J, Delaney AD, Zhao Y, Astell C, Asano J, Babakaiff R, Barber S, Beland
J, Bohacec S, Brown-John M, Chand S, Charest D, Charters AM, Cullum R,
Dhalla N, Featherstone R, Gerhard DS, Hoffman B, Holt RA, Hou J, Kuo BY,
Lee LL, Lee S, Leung D, Ma K, Matsuo C, Mayo M, McDonald H, Prabhu AL,
Pandoh P, Riggins GJ, de Algara TR, Rupert JL, Smailus D, Stott J, Tsai
M, Varhol R, Vrljicak P, Wong D, Wu MK, Xie YY, Yang G, Zhang I, Hirst
M, Jones SJ, Helgason CD, Simpson EM, Hoodless PA, & Marra MA. A mouse
atlas of gene expression: large-scale digital gene-expression profiles
from precisely defined developing C57BL/6J mouse tissues and cells. Proc
Natl Acad Sci U S A 102 (51): 18485-90, 2005.
View Abstract
Noseda M, McLean G,
Niessen K, Chang L, Pollet I, Montpetit R, Shahidi R, Dorovini-Zis K, Li
L, Beckstead B, Durand RE, Hoodless PA, & Karsan A. Notch activation
results in phenotypic and functional changes consistent with
endothelial-to-mesenchymal transformation. Circ Res 94 (7): 910-7, 2004.
View Abstract
Hoodless
PA, Pye M, Chazaud C, Labbe E, Attisano L, Rossant J, & Wrana JL. FoxH1
(Fast) functions to specify the anterior primitive streak in the mouse.
Genes Dev 15 (10): 1257-71, 2001.
View Abstract
Sirard C, Kim S,
Mirtsos C, Tadich P, Hoodless PA, Itie A, Maxson R, Wrana JL, & Mak TW.
Targeted disruption in murine cells reveals variable requirement for
Smad4 in transforming growth factor beta-related signaling. J Biol Chem
275 (3): 2063-70, 2000.
View Abstract
Tremblay KD,
Hoodless
PA, Bikoff EK, & Robertson EJ. Formation of the definitive endoderm in
mouse is a Smad2-dependent process. Development 127 (14): 3079-90, 2000.
View Abstract
Hoodless PA, Tsukazaki T, Nishimatsu S, Attisano L, Wrana JL, & Thomsen GH.
Dominant-negative Smad2 mutants inhibit activin/Vg1 signaling and
disrupt axis formation in Xenopus. Dev Biol 207 (2): 364-79, 1999.
View Abstract
Hoodless PA, & Wrana
JL. Mechanism and function of signaling by the TGF beta superfamily.
Curr Top Microbiol Immunol 228: 235-72, 1998.
View Abstract
Labbe
E, Silvestri C, Hoodless PA, Wrana JL, & Attisano L. Smad2 and Smad3
positively and negatively regulate TGF beta-dependent transcription
through the forkhead DNA-binding protein FAST2. Mol Cell 2 (1): 109-20,
1998.
View Abstract
Macias-Silva M,
Hoodless PA, Tang SJ, Buchwald M, & Wrana JL. Specific activation of
Smad1 signaling pathways by the BMP7 type I receptor, ALK2. J Biol Chem
273 (40): 25628-36, 1998.
View Abstract
Tang SJ,
Hoodless PA,
Lu Z, Breitman ML, McInnes RR, Wrana JL, & Buchwald M. The Tlx-2
homeobox gene is a downstream target of BMP signalling and is required
for mouse mesoderm development. Development 125 (10): 1877-87, 1998.
View Abstract
Waldrip WR, Bikoff
EK, Hoodless PA, Wrana JL, & Robertson EJ. Smad2 signaling in
extraembryonic tissues determines anterior-posterior polarity of the
early mouse embryo. Cell 92 (6): 797-808, 1998.
View Abstract
Hoodless PA,
Hemmati-Brivanlou A. Inhibitory
control of neural differentiation in mammalian cells.
Development, Genes and Evolution 207:19-28, 1997.
View
Abstract
Li M, Li J,
Hoodless
PA, Tzukazaki T, Wrana JL, Attisano L, & Tsang BK. Mothers against
decapentaplegic-related protein 2 expression in avian granulosa cells is
up-regulated by transforming growth factor beta during ovarian
follicular development. Endocrinology 138 (9): 3659-65, 1997.
View Abstract
Eppert K, Scherer SW,
Ozcelik H, Pirone R, Hoodless P, Kim H, Tsui LC, Bapat B, Gallinger S,
Andrulis IL, Thomsen GH, Wrana JL, & Attisano L. MADR2 maps to 18q21 and
encodes a TGFbeta-regulated MAD-related protein that is functionally
mutated in colorectal carcinoma. Cell 86 (4): 543-52, 1996.
View Abstract
Hoodless PA, Haerry
T, Abdollah S, Stapleton M, O’Connor MB, Attisano L, & Wrana JL. MADR1,
a MAD-related protein that functions in BMP2 signaling pathways. Cell 85
(4): 489-500, 1996.
View Abstract
Macias-Silva M, Abdollah S,
Hoodless PA, Pirone R, Attisano L, & Wrana JL. MADR2 is a
substrate of the TGFbeta receptor and its phosphorylation is required
for nuclear accumulation and signaling. Cell 87 (7): 1215-24, 1996.
View Abstract
Duncan
SA, Manova K, Chen WS, Hoodless P,
Weinstein
DC,
Bachvarova RF, & Darnell JE, Jr. Expression of transcription factor
HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the
developing mouse embryo: HNF-4 is a marker for primary endoderm in the
implanting blastocyst. Proc Natl Acad Sci U S A 91 (16): 7598-602, 1994.
View Abstract
Weinstein
DC,
Ruiz i Altaba A, Chen WS, Hoodless P, Prezioso VR, Jessell TM, & Darnell
JE, Jr. The winged-helix transcription factor HNF-3 beta is required for
notochord development in the mouse embryo. Cell 78 (4): 575-88, 1994. View Abstract
Hoodless PA, Ryan AK,
Schrader TJ, & Deeley RG. Characterization of liver-enriched proteins
binding to a developmentally demethylated site flanking the avian
apoVLDLII gene. DNA Cell Biol 11 (10): 755-65, 1992.
View Abstract
Hoodless PA, Roy RN,
Ryan AK, Hache RJ, Vasa MZ, & Deeley RG. Developmental regulation of
specific protein interactions with an enhancerlike binding site far
upstream from the avian very-low-density apolipoprotein II gene. Mol
Cell Biol 10 (1): 154-64, 1990.
View Abstract
Lab Members
Open Position
We are currently accepting post-doctoral and graduate student
applications
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Mailing Address:
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Terry Fox Laboratory
BC Cancer Agency
675 West 10th
Avenue,
Vancouver BC
Canada V5Z 1L3 |
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Email: |
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hoodless@bccrc.ca |
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Phone Numbers: |
Tel: 604-675-8133
Fax: 604-877-0712
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Terry Fox Laboratory
BC Cancer Agency
675 West 10th
Avenue,
Vancouver BC
Canada V5Z 1L3 |
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