Kimberly D. Tremblay

Kimberly D. Tremblay, Ph.D.

Associate Professor

Honors Program Director

Photo of Kimberly Tremblay

Office phone: 413-545-5560

Lab phone: 413-545-2339

Fax: 413-545-6326

Email: kdtrembl [at] vasci [dot] umass [dot] edu

Office location: 427C ISB

A.B.: Smith College, 1992

Ph.D.: University of Pennsylvania, 1998 (Marisa Bartolomei’s lab)

Postdoctoral Training:
Harvard University, 1998- 2001
(Liz Robertson’s Lab)
Fox Chase Cancer Center
(Ken Zaret’s Lab, 2001-2004)

Postdoctoral Awards: NRSA Postdoctoral Fellowship 1998-2001, NIH K01 Mentored Research Award 2003-2006

- Animal Genetics

ANIMLSCI 494TI - Departmental Honors Thesis IE

ANIMLSCI 697J - Genes, Cells and Development

Mouse Development and Organogenesis

In our lab we study the development of the definitive endoderm, one of the 3 primary germ layers that arises during gastrulation. The definitive endoderm produces the entire gastrointestinal tract as well as accessory digestive and respiratory organs. These organs include lung, liver, pancreas, thyroid, parathyroid and thymus. Although much is known about the genes involved in the function of these organs in the adult, relatively little is known about how these tissues are initially patterned and organized. An overall goal of the lab is to understand the morphological and molecular mechanisms that give rise to endodermal organs, focusing on liver and pancreas. Towards this end, we are taking two broad approaches to study the early stages of endoderm organogenesis in the mouse. They can be defined as embryological approaches, utilizing whole embryo culture, and genetic approaches, using transgenic and homologous recombination to create favorable environments to study this fascinating tissue layer.

Identification and Manipulation of Liver and Pancreas Precursors

The endoderm is a uniform epithelial layer that covers the ventral surface of the pre-somitic mouse embryo. From 8-15 somites (S), the accessory organs appear, in a temporally and spatially characteristic manner, as thickenings in this epithelium.

Figure 1: Early stages of endoderm organogenesis.

Figure 2: Whole embryo culture. Organ-specific gene expression follows or is coincident with the onset of these morphological processes and as a result, little is known about the location of these organ progenitors in the endodermal sheet, the morphological processes leading to organogenesis, or the molecular mechanisms that initiate organogenesis. Because of the lack of genes or promoters expressed specifically in the endoderm, more traditional approaches, such as knock-out and transgenic experiments, have had limited success in tackling these issues. We have decided to use a whole embryo culture system in which we can successfully culture whole embryos, and their accompanying extraembryonic tissues, from early somite stages (~day 8.25) until day 10 (Fig. 2). Culturing allows us to manipulate the pre-specified (d8.25) endoderm and follow these changes through d10, when the liver and pancreas buds have formed and begun to differentiate. We have used viable dyes to identify precursor populations in the early somite embryo and are now using electroporation to identify genes that disrupt early organogenesis.

Clonal Analysis of Organ Growth 

Little is known about the growth or developmental potential of early individual endodermal cells. Is an individual endodermal cell committed to a specific organ or is it capable of giving rise to cells contributing to multiple organs? Similarly, it is unknown whether individual cells expressing organ-specific markers are capable of giving rise to all differentiated cell-types within the organ or are excluded from certain lineages. To answer these questions we perform experiments with transgenic or knock-in mice that produce embryos that have had individual endoderm cells marked with either the fluorescent markers EGFP or the histological marker LacZ. By retrospectively analyzing the clonal descendants of these cells, we will elucidate the normal processes that give rise to endodermal organ, further define organ precursors and understand the morphological processes that produce the mature organs.

Sebae GEK, Malatos JM, Cone M-KE, Rhee S, Angelo JR, Mager J, Tremblay KD.  2018.  Single-cell murine genetic fate mapping reveals bipotential hepatoblasts and novel multi-organ endoderm progenitors. Development. 145:dev168658.
Palaria A, Angelo JR, Guertin TM, Mager J, Tremblay KD.  2018.  Patterning of the hepato-pancreatobiliary boundary by BMP reveals heterogeneity within the murine liver bud. Hepatology. 68:274–288.
Cui W, Marcho C, Wang Y, Degani R, Golan M, Tremblay KD, Rivera-Pérez J, Mager J.  2018.  Med20 is essential for early embryogenesis and regulates Nanog expression. Reproduction.
Cui W, Dai X, Marcho C, Han Z, Zhang K, Tremblay KD, Mager J.  2016.  Towards Functional Annotation of the Preimplantation Transcriptome: An RNAi Screen in Mammalian Embryos. Scientific Reports. 6
Marcho C, Bevilacqua A, Tremblay KD, Mager J.  2015.  Tissue-specific regulation of Igf2r/Airn imprinting during gastrulation.. Epigenetics Chromatin. 8:10.
Rhee S, Guerrero-Zayas M-I, Wallingford MC, Ortiz-Pineda P, Mager J, Tremblay KD.  2013.  Visceral endoderm expression of Yin-Yang1 (YY1) is required for VEGFA maintenance and yolk sac development.. PLoS One. 8(3):e58828.
Tremblay KD.  2011.  Inducing the liver: understanding the signals that promote murine liver budding.. Journal of cellular physiology. 226(7):1727-31.
Griffith GJ, Trask MC, Hiller J, Walentuk M, Pawlak JB, Tremblay KD, Mager J.  2011.  Yin-yang1 is required in the mammalian oocyte for follicle expansion.. Biology of reproduction. 84(4):654-63.
Nicholls SB, Chu J, Abbruzzese G, Tremblay KD, Hardy JA.  2011.  Mechanism of a genetically encoded dark-to-bright reporter for caspase activity.. The Journal of biological chemistry. 286(28):24977-86.
Tremblay KD.  2010.  Formation of the murine endoderm: lessons from the mouse, frog, fish, and chick.. Progress in molecular biology and translational science. 96:1-34.
Malcuit C, Trask MC, Santiago L, Beaudoin E, Tremblay KD, Mager J.  2009.  Identification of novel oocyte and granulosa cell markers.. Gene expression patterns : GEP. 9(6):404-10.
Bort R, Signore M, Tremblay K, Martinez Barbera JP, Zaret KS.  2006.  Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development.. Developmental biology. 290(1):44-56.
Calmont A, Wandzioch E, Tremblay KD, Minowada G, Kaestner KH, Martin GR, Zaret KS.  2006.  An FGF response pathway that mediates hepatic gene induction in embryonic endoderm cells.. Developmental cell. 11(3):339-48.
Tremblay KD, Dunn NR, Robertson EJ.  2001.  Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation.. Development (Cambridge, England). 128(18):3609-21.
Tremblay KD, Hoodless PA, Bikoff EK, Robertson EJ.  2000.  Formation of the definitive endoderm in mouse is a Smad2-dependent process.. Development (Cambridge, England). 127(14):3079-90.
Name Phone Office
El Sebae , Gabriel ABBS Graduate Student 413-545-2339 ISB 455