Research interests

My laboratory is interested in understanding how blood vessels develop during embryogenesis and repair themselves following vascular injury. We have recently focused on the family of Notch receptors, which have been shown to be highly expressed in large vessels during remodeling. Our goals are to understand the pathways by which Notch receptor signaling controls smooth muscle cell and endothelial cell behavior. These studies apply to human diseases including restenosis, atherosclerosis, and other vascular obstructive diseases. In addition, blood vessel recruitment and growth is a hallmark of successful tumors, and we are interested in signals that increase tumor cell growth and survival.

One of our strategies is to create murine genetic transgenic models in which we can activate or inhibit Notch receptor signaling in a vascular-specific manner. These models will allow us to develop in vivo systems to understand blood vessel remodeling and tumor growth.

I also direct the the Mouse Transgenic and In Vivo Imaging Core Facility at Maine Medical Center Research Institute, which is a resource for the generation of transgenic and gene-targeted models. This service allows investigators to submit transgenes of interest for pronuclear injection to obtain transgenic animals, or target specific genes in embryonic stem cells. Other resources available through this Core Facility are cryoprotection of mouse lines, re-derivation, embryo staging and collection, and maintenance of shared strains for investigator use. The Small Animal Magnetic Resonance Imaging (MRI) component of the facility is run by my colleague Ilka Pinz, Ph.D. We also have capacity for dual energy X-ray absorptiometry (DXA), high resolution ultrasound, and microcomputed tomography (microCT) as part of our imaging services.

Publications

• Plumer A, Duan H, Subramaniam S, Lucas FL, Miesfeldt S, Ng AK, Liaw L. Development of fragment-specific osteopontin antibodies and ELISA for quantification in human metastatic breast cancer. BMC Cancer. 2008 Jan 31;8:38.

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• Miceli-Libby L, Johnson MJ, Harrington A, Hara-Kaonga B, Ng AK, Liaw L. Widespread delta-like-1 expression in normal adult mouse tissue and injured endothelium is reflected by expression of the Dll1LacZ locus. J Vasc Res. 2008;45(1):1-9.

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• Tang Y, Urs S, Liaw L. Hairy-related transcription factors inhibit Notch-induced smooth muscle alpha-actin expression by interfering with Notch intracellular domain/CBF-1 complex interaction with the CBF-1-binding site. Circ Res. 2008 Mar 28;102(6):661-668.

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• Venkatesh DA, Park KS, Harrington A, Miceli-Libby L, Yoon JK, Liaw L. Cardiovascular and hematopoietic defects associated with Notch1 activation in embryonic Tie2-expressing populations. Circ Res. 2008 Aug 15;103(4):423-431.

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• Urs S, Roudabush A, O'Neill CF, Pinz I, Prudovsky I, Kacer D, Tang Y, Liaw L, Small D. Soluble forms of the Notch ligands Delta1 and Jagged1 promote in vivo tumorigenicity in NIH3T3 fibroblasts with distinct phenotypes. Am J Pathol. 2008 Sep;173(3):865-878.

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• O'Neill CF, Urs S, Cinelli C, Lincoln A, Nadeau RJ, Leon R, Toher J, Mouta-Bellum C, Friesel RE, Liaw L. Notch2 signaling induces apoptosis and inhibits human MDA-MB-231 xenograft growth. Am J Pathol. 2007 Sep;171(3):1023-1036.

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• Havrda MC, Johnson MJ, O'Neill CF, Liaw L. A novel mechanism of transcriptional repression of p27kip1 through Notch/HRT2 signaling in vascular smooth muscle cells. Thromb Haemost. 2006 Sep;96(3):361-370.

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• Urs S, Harrington A, Liaw L, Small D. Selective expression of an aP2/Fatty Acid Binding Protein 4-Cre transgene in non-adipogenic tissues during embryonic development. Transgenic Res. 2006 Oct;15(5):647-53.

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• Hara-Kaonga B, Gao YA, Havrda M, Harrington A, Bergquist I, Liaw L. Variable recombination efficiency in responder transgenes activated by cre recombinase in the vasculature. Transgenic Res. 2006 Feb;15(1):101-106.

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Community/University Service

Other Experience

2004-present Ad Hoc Reviewer, Vascular Cell and Molecular Biology (VCMB) Study Section, NIH

2005-present Member, Southern Maine Leadership Council, American Heart Association, Maine

2006-present Ad Hoc Reviewer, NIGMS, NIH

2006-present Ad Hoc Reviewer, NIDDK, NIH

2006 Reviewer, NEA1, Northeast Consortium, American Heart Association

2007-present Ad Hoc Reviewer, Cardiovascular Differentiation and Disease (CDD) Study Section, NIH

2008-present Vice Chair, American Heart Association Founders Affiliate Research Committee

2008-present Member, American Heart Association Fouders Affiliate Board of Directors

 

Graduate Student Trainees

Daniel L. Myers, Ph.D. (Mentor) UMaine, BMMB, Ph.D. 2004

Penny (Russell) Glacy, M.S. (Co-Mentor) UMaine, Functional Genomics M.S. 2004

Matthew C. Havrda, Ph.D. (Mentor) UMaine, BMMB, Ph.D. 2005

Sheila Hongyi Duan, M.S. (Co-Mentor) Univ. Southern Maine, Applied Med. Sci. M.S. 2006

Christine O'Neill, Ph.D. (Mentor) UMaine, BMMB, Ph.D. 2007

Alicia Plumer, M.S. (Co-Mentor) Univ. Southern Maine, Applied Med. Sci. M.S. 2008

Yuefeng Tang, M.S. (Mentor) Current student, UMaine, BMMB

 

Postdoctoral Trainees

Renu Agnihotri, M.D. 2000-2003

Yu Alice Gao, Ph.D. 2001-2003

Bochiwe Hara-Kaonga, Ph.D. 2003-2007

Sumithra Urs, Ph.D. 2004-2008

Deepak Venkatesh, Ph.D. 2006-present

Sarah Peterson, M.D. 2008-present

 

Visiting Scientist Trainees

Lymari Funetes Claudio, Ph.D. summer 2006 and summer 2007

 

Course Participation

Fall 2001, Lecturer, AIM680 USM, Molecular Basis of Disease

2003-2004, Course Co-Coordinator, BMB550 UMaine, Cell Biology

Spring 2003, Course Co-Coordinator, BMB580, Special Topics in Cell Biology

Spring 2005, Lecturer, AIM620 USM, Molecular Immunology

Spring 2006, Course Co-Coordinator, BMB580 UMaine, Special Topics in Cell Biology "Time in Cell Biology"

Spring 2006, Course Co-Coordinator, BMB550 UMaine, Cell Biology of Tissue Development and Function

Spring 2006, Lecturer, AIM680 USM, Molecular Basis of Disease

Fall 2006, Lecturer, BCM790 Univ. New Hampshire, Topics in Biomedicine

Spring 2007, Course Co-Coordinator, BMB550 UMaine, Cell Biology of Tissue Development and Function

Spring 2007, Lecturer, AIM680 USM, Molecular Basis of Disease

Fall 2007, Research Mentor, AMS693 USM, Advanced Research Techniques in Biomedical Science

Fall 2007, Lecturer, BCM790 Univ. New Hampshire, Topics in Biomedicine

5/4/07, Laboratory Coordinator, AMS551 USM, Immunology Laboratory

Spring 2008, BMS690 UMaine (BIO610 Univ. New England), Course Coordinator, Instrumentation Techniques in Cell/Molecular Biology

Spring 2008, Course Co-Coordinator, BMB550 UMaine, Cell Biology of Tissue Development and Function

Spring 2008, Guest Speaker BIO312 Univ. Southern Maine, Microbiology Laboratory

Fall 2008, Lecturer, BCM790 Univ. New Hampshire, Topics in Biomedicine