Lucy Liaw, PhD

Faculty Scientist III
Director, Research Training Programs
Director, Mouse Genome Modification Core 

EDUCATION

BS: Biology, University of Arizona
PhD: Biological Structure, University of Washington, Seattle
Postdoctoral Training: Cell Biology & Cardiology, Vanderbilt University

Liaw Lab

Tackling cardiometabolic disease

Cardiovascular disease is the leading cause of mortality in our country, and the obesity epidemic has amplified this public health problem. Our research focuses on cellular interactions and signaling and molecular mechanisms that impact cardiovascular disease. In particular, we are interested in cells of the vessel wall and the surrounding perivascular adipose tissue (PVAT). The blood vessel and surrounding adipose tissue form a local vascular microenvironment that regulates susceptibility to vascular disease. To study these interactions, we are identifying protein signatures of PVAT in human donors with different levels of cardiovascular disease, and also using mouse models of obesity and vascular disease. Conversely, our mouse models also allow us to evaluate PVAT in the context of anti-aging dietary conditions, such as methionine restriction or calorie restriction. Using these models, we are studying adipose progenitor cell characteristics, differentiation capacity, PVAT phenotype, and effects on vascular physiology.

Our laboratory also runs our institutional Mouse Genome Modification Resource, and develop mouse models of human disease using CRISPR/Cas techniques and traditional transgenic microinjection procedures. We perform gene/protein analysis and develop research plans for targeting, as well as develop molecular reagents, perform microinjection, and establish and perform initial genotyping. Other services include a mouse germplasm cryopreservation program and a re-derivation program.

A fully differentiated 3D adiposphere stained for Actin filaments (green), lipids (red) and nuclei (blue).
Notch3 co-localization with contractile SMC in atherosclerotic lesion. Aorta sections from a Myh11-CreERT2 ROSA floxed STOP eYFP Apoe−/− SMC lineage tracing mouse with advanced atherosclerotic lesion was immunostained for Notch3/GFP with DAPI nuclear staining in blue. Yellow arrowheads indicate Notch3 positive SMC in the fibrous cap while cyan arrowhead indicates a Notch3 negative cell of SMC origin. Scale bar is 50 μm.
Rab27a and lipid specific staining in a 3D adiposphere.  An adiposphere is a 3D model of adipose tissue.  Rab27a (red) is a trafficking molecule implicated in adipogenesis.  Perilipin (white) and lipidTOX (green) are lipid markers.

Lucy Liaw, PhD

Faculty Scientist
Lucy.Liaw@mainehealth.org
I have run a research program at Maine Medical Center for over 20 years, focusing on understanding regulators of cardiovascular disease. My current responsibilities also include overseeing our Mouse Genome Modification shared resource and directing our Research Training programs. I also lead a Center of Biomedical Research Excellence in Metabolic Networks, and in this capacity mentor early career investigators and oversee additional shared resources. I am inspired by my outstanding research team and all of the other dedicated individuals that it takes to run a successful research operation

Anne Harrington, BS

Technology Manager
Anne.Harrington@mainehealth.org
 

Abby Kaija

Research Assistant II
Abigail.Kaija@mainehealth.org

I am a Research Assistant focused on the molecular biology aspect of generating novel mouse models through genotyping mouse strains and maintaining records for the mouse colony. I also practice mouse procedures important to the Mouse Genome Modification Core. On days I’m not biking into work at the Institute, I love to hike/ski, explore new recipes in my kitchen, and watercolor.

Maryam Mahdi

Academic Intern

I am a student intern from the University of Southern Maine. I am exploring research and learning new techniques at the Liaw Lab. My project focuses on the effects of methionine restriction on PVAT cells’ proliferation and differentiation.

Kimberly Malka, MD, PhD

Vascular Surgeon
Kimberly.Malka@mainehealth.org

 

Marissa McGilvrey, BS

Graduate Student

I am interested in how we can modify diet composition to maintain metabolic health of PVAT to improve cardiovascular function. My studies focus on how dietary restriction of an essential amino acid, Methionine, is able to facilitate healthy PVAT despite a high fat diet.

 

Larisa Ryzhova, MD, PhD

Scientific Manager
Larisa.Ryzhova@mainehealth.org

Ashley Soucy, BS

Graduate Student
ashley.n.soucy@maine.edu
As a GSBSE graduate student in the Liaw Lab, my primary interest is understanding how exosomes mediate communication between perivascular adipose tissue (PVAT) to cardiovascular cells to promote disease.

Katie Stieber, BS

Graduate Student
Caitlin.Stieber@mainehealth.org
I am a 2nd year PhD student in the Graduate School of Biomedical Science and Engineering at the University of Maine.  I am interested in understanding how perivascular adipose tissue (PVAT) expands and how this expansion affects the underlying vessel wall. I am using several 3D cell culture models to make in vitro models of human PVAT derived from donors at MMC.

Benjamin Tero, BS

Research Assistant III
Benjamin.Tero@mainehealth.org
I am a recent graduate of the University of Maine with a BS in Biochemistry working as a research assistant in the Liaw Lab. While assisting others with their projects, I will be working to create primary cell culture lines from a variety of human surgical samples obtained from donors at MMC. These cell lines will be used to help understand changes in perivascular adipose tissue (PVAT) seen under varying conditions of cardiovascular disease.

Chenhao Yang, MRes

Graduate Student
Chenhao.Yang@mainehealth.org

Xuehui Yang

Staff Scientist
Xuehui.Yang@mainehealth.org

My research interest is to elucidate the mechanisms of pathogenesis of cardiovascular diseases. My focus is on the regulation of vascular smooth muscle cell (VSMC) phenotypic remodeling.VSMCs are localized in the tunica media of the vasculature

and responsible for regulating arterial tone, blood pressure, and blood supply of the tissues. However, under pathological or stressed conditions, VSMCs undergo phenotypic switching, and contribute to multiple cardiovascular diseases such as atherosclerosis, hypertension and arterial aneurysms. My goal is to identify disease related VSMC phenotypes, and the underlying signaling pathways. 

Caption photo left: Multicolor RNA Scope analysis for Spry1, PDGFRb, and Sca1 mRNA expression demonstrates a colonial VSMC up-regulation of Sca1, a mesenchymal marker, under hypercholesterolemia condition in SMC-specific Spry1 knockout mice. White arrowheads indicate Sca1 expressing VSMC in vessel media layer

Liaw Lab Alumni 

Bethany Fortier BS – IDEXX Laboratories
Dylan Blackington BS – Technical Manufacturing Chemist, Abbott Diagnostics
Beau Rostama PhD – Scientist II, Cell Biology/Cell Line Engineering, Artemys Foods
Sumithra Urs PhD – Senior Scientist, Labcorp Drug Development
Yuefeng Tang PhD – Data Scientist, Center of Excellence in Wireless and Information Technology, Stony Brook University
Renu Agnihotri MD – Chief Academic Officer, American University of Integrative Sciences, School of Medicine
Christine Nadeau PhD (O’Neill) –  Program Director at National Cancer Institute, NIH
Jackie Turner BA –  Medical Student, Philadelphia College of Osteopathic Medicine
Penny Clum, MS – Research Associate, Duke Cancer Institute
Samantha White BS – Quality Control Collaboratory, USM
Joshua Boucher PhD – Senior Scientist, Infectious Disease, IDEXX Laboratories
Su Su PhD – Staff Scientist, MaineHealth Institute for Research
Beau Rostama PhD – Research Associate, Univ. New England
Sarah Peterson MD, PhD – Manager, Clinical Research, R&D, IDEXX Laboratories
Deepak Venkatesh PhD – Scientist, Merck Serono
Vance Holt III, PhD – Research Scientist, Pediatric Translational Research Branch, NIAMS, NIH
Sumithra Urs PhD – Scientist, Scientific Development, Covance
Darrin Ramsdell MS – Scientist, IDEXX Laboratories
Betsy Cope MS – Oncology Account Manager, Advanced Accelerator Applications
Yuefeng Tang PhD – Research Fellow, Univ. Massachusetts Medical School
Bochiwe Hara-Kaonga PhD
Allson Gurney MS – Scientist, University of Minnesota
Alicia Plumer MS – Biochemist, Siemens Healthcare Diagnostics
Alice Gao PhD – Product Manager, Agilent Technologies
Renu Agnihotri MD – Chief Academic Officer, American University of Integrative Sciences, School of Medicine
Christine O’Neill PhD – Research Scientist, Madigan Army Medical Center
Michael Johnson MS – Environmental Inspector, ERM, ONEOK
Sheila Duan MS – Clinical Label Management Consultant, Eli Lilly and Company
Matthew Havrda PhD – Assistant Professor, Molecular and Systems Biology, Geisel School of Medicine at Dartmouth
Daniel Myers PhD – Attorney

Recent Interns

Christian Potts, post-bacc researcher summer 2021
Ginger Paquette, USM academic year intern and summer student, 2020-2021
Benjamin Tero, UMaine undergraduate researcher summer 2019
Bethany Fortier, USM academic year intern 2018-2019
Grace Reynolds, Williams College undergraduate researcher summer 2018
Sharon Jordan, Maine INBRE summer student 2018
Spencer Scott, MaineTrack medical student, summer 2018
Samantha White, USM academic year intern 2017-2018, and summer 2018
Beth Ash, USM academic year intern 2017-2018
Katie Stieber, Cornell College undergraduate researcher summer 2017
Nicholas Hagler, Waynflete School summer intern, 2017
Elliot Youth, Brown University summer intern, 2017

Bethany presented her research in October 2019 at the OFAS Symposium on Healthy Aging.

Lucy presented lab research at the Notch XI meeting in Athens in October 2019. Acropolis at dusk.

Larisa and Ashley cleaning the lab fridge after we moved into our new lab –Sept. 2019

Five new graduate students started thesis research in Fall 2019 at MaineHealth Institute for Research. From left: Mariah Farrell (Reagan lab), Bethany Fortier (Liaw lab), Ashley Soucy (Liaw lab), Samantha Costa (Reagan lab), and Katie Stieber (Liaw lab).

At the annual retreat of the Graduate School of Biomedical Science and Engineering. Ashley and Katie with Sarah Holbrook (Mentor: Greg Cox, JAX). Congratulations to Katie and Sarah for each earning a spot on the new UMaine T32 program for the 2019-2020 academic year!

Our 2019 summer student was Ben Tero, a University of Maine student. Ben worked on characterizing a novel Rab27a null mouse strain that was initially generated and in the lab by Larisa and Anne.

All dressed up for Jess’ graduation ceremony at Tufts University in May 2019. Jess earned her PhD from the Cell, Molecular & Developmental Biology program at the Sackler School of Graduate Biomedical Sciences.

A complete list of publications can be found on My NCBI

Yang X, Yang C, Friesel R, Liaw L. 2022. Sprouty1 has a protective role in atherogenesis and modifies the migratory and inflammatory phenotype of vascular smooth muscle cells. Submitted to ATVB

Tero BW, Fortier B, Soucy AN, Paquette G, Liaw L. Quantification of lipid area within thermogenic mouse perivascular adipose tissue using standardized image analysis in FIJI. J Vascular Res 2021, in press.

Angueira AR, Sakers AP, Holman CD, Cheng L, Arbocco MN, Shamsi F, Lynes MD, Shrestha R, Okada C, Batmanov K, Susztak K, Tseng Y-H, Liaw L, Seale P. Defining the lineage of thermogenic perivascular adipose tissue. Nat Metab 2021 3(4):469-484.

Boucher JM, Ryzhova L, Harrington A, Davis-Knowlton J, Turner JE, Cooper E, Maridas D, Ryzhov S, Rosen CJ, Vary CPH, Liaw L. Pathological conversion of mouse perivascular adipose tissue by Notch activation. Arterioscler, Thromb, Vasc Biol, 2020, 40(9):2227-2243. PMCID: PMC7483939.

Dickson D, Stohn P, Rodriguez LS, Hernandez A, Harrington A, Liaw L, Feig LA. Involvement of early embryonic miR-409-3p in the establishment of anxiety levels in female mice. Dev Neurobiol 2020, 80(5-6):160-167.

Stieber K, Malka K, Boucher JM, Liaw L. Human perivascular adipose tissue as a regulator of vascular microenvironment and coronary artery and aortic disease. J Cardiology and Cardiovasc Sci 2019, 3(4):10-15. PMCID: PMC7224402.

Channabasavaiah G…Liaw L, Miano JM, Burgio G. Reproducibility of CRISPR-Cas9 Methods for generation of conditional mouse alleles: a multi-center evaluation. Genome Biol, 2019, 20(1):171.

Scott SS, Yang X, Robich M, Liaw L, Boucher JM. Differentiation capacity of human aortic perivascular adipose progenitor cells. J Vis Exp 2019, 145, e59337, doi:10.3791/59337.

Su S, Guntur AR, Nguyen DC, Fakory SS, Doucette CC, Leech C, Lotana H, Kelley M, Kohli J, Martino J, Sims-Lucas S, Liaw L, Vary C, Rosen CJ, Brown AC. A renewable source of human beige adipocytes for development of therapies to treat metabolic syndrome. Cell Reports 2018.

Boucher JM, Robich M, Scott SS, Yang X, Ryzhova L, Turner JE, Pinz I, Liaw L. Rab27a regulates human perivascular adipose progenitor cell differentiation. Cardiovascular Drugs and Therapy: PVAT Biology 2018, 32(5):519-530.

Peterson SM, Turner JE, Harrington A, Davis-Knowlton J, Lindner V, Gridley T, Vary CPH, Liaw L. Notch2 and proteomic signatures in mouse neointimal lesion formation. Arterio Thromb Vasc Biol 2018, 38(7):1576-1593, NIHMSID 968681.

Davis-Knowlton J, Turner JE, Turner A, Damian-Loring S, Hagler N, Henderson T, Emery IF, Duarte CW, Vary CPH, Eldrup-Jorgensen J, Liaw L. Characterization of smooth muscle cells from human atherosclerotic lesions and their responses to Notch signaling. Laboratory Investigation 2018, 38(7):1576-1593.

Yang X*, Gong Y, He Q, Licht JD, Liaw L, Friesel RE*. 2018. Loss of Spry1 attenuates vascular smooth muscle proliferation by impairing mitogen-mediated changes in cell cycle regulatory circuits. J Cell Biochem. Apr; 119(4):3267-3279. PMCID:PMC5826877. *: co-corresponding author.

Liaw L, Freedman JE, Becker LB, Mehta NN, Liscum L. Peer review practices for evaluating biomedical research grants: a scientific statement from the American Heart Association. Circ Res 2017, 121(4):e9-e19.

Bishop KA, Harrington A, Kouranova E, Weinstein EJ, Rosen CJ, Cui X, Liaw L. CRISPR/Cas9 mediated insertion of loxP sites in the mouse Dock7 gene provides an effective alternative to use of targeted embryonic stem cells. G3: Genes, Genomes, Genetics 2016, 6:2051-2061.

Liaw L, Prudovsky I, Koza RA, Anunciado-Koza RV, Siviski ME, Lindner V, Friesel RE, Rosen CJ, Baker PR, Simons B, Vary CP. Lipid profiling of in vitro cell models of adipogenic differentiation: relationships with mouse adipose tissues. J Cell Biochem 2016 117:182-193.

He Q, Jing H, Liaw L, Gower L, Vary C, Hua S, Yang X. 2016. Suppression of Spry1 inhibits triple-negative breast cancer malignancy by decreasing EGF/EGFR mediate mesenchymal phenotype. Sci Rep; Mar;15(6):23216.

Jing H, Liaw L, Friesel R, Vary C, Hua S, Yang X. 2016. Suppression of Spry4 enhances cancer stem cell properties of human MDA-MB-231 breast carcinoma cells. Cancer cell international. 16:19. PMCID: PMC4787021.

Rostama B, Turner JE, Seavey GT, Norton CR, Gridley T, Vary CPH, Liaw L. DLL4/Notch1 and BMP9 interdependent signaling induces human endothelial cell quiescence via P27KIP1 and thrombospondin-1. Arter Thromb Vasc Biol 2015, 35(12):2626-2637. PMID: 26471266

Rostama B, Peterson SM, Vary CPH, Liaw L. Notch signal integration in the vasculature during remodeling. Vasc Pharmacol 2014, 63:97-104. NIHMSID #636614.

Boucher JM, Harrington A, Rostama B, Lindner V, Liaw L. A receptor-specific function for Notch2 in mediating vascular smooth muscle cell growth arrest through p27kip1. Circ Res 2013, 113:975-985. PMCID: PMC3882755.

Tang Y, Bai H, Urs S, Wang Z, Liaw L. Notch1 activation in embryonic VE-cadherin populations selectively blocks hematopoietic stem cell generation and fetal liver hematopoiesis. Transgenic Res 2013, 22:403-410. PMCID: PMC3594084.

Young K, Conley B, Romero D, Tweedie E, O’Neill C, Pinz I, Brogan L Lindner V, Liaw L, Vary CP. BMP9 regulates endoglin-dependent chemokine responses in endothelial cells. Blood 2012, 120:4263-4273. PMCID:PMC3501721.

Urs S, Henderson T, Le P, Rosen CJ, Liaw L. Tissue specific expression of Sprouty1 in mice protects against high fat diet induced fat accumulation, bone loss, and metabolic dysfunction. Br J Nutrition 2012, 6:1-9. NIHMSID #415296.

Tang Y, Boucher JM, Liaw L. Histone deacetylase activity selectively regulates Notch-mediated smooth muscle differentiation in human vascular cells. J Amer Heart Assoc 2012, Jun;1(3):e000901, PMCID: PMC3487326.

Urs S, Turner B, Tang Y, Rostama B, Small D, Liaw L. Effect of soluble Jagged-1- mediated inhibition of Notch signaling on proliferation and differentiation of an adipocyte progenitor cell model. Adipocyte 2012, 1:46-57.

Boucher J, Gridley T, Liaw L. Molecular pathways of Notch signaling in vascular smooth muscle cells. Frontiers in Physiology, 2012, 3:81. PMCID: PMC3151075.

Boucher JM, Peterson, SM, Urs S, Zhang C, Liaw L. The miR143/145 cluster is a novel transcriptional target of Jagged-1/Notch signaling in vascular smooth muscle cells. J Biol Chem 2011, 286:28312-28321. PMCID:PMC3151075.

Tang Y, Yang X, Friesel RE, Vary CPH, Liaw L. Mechanisms of TGFbeta induced differentiation in human vascular smooth muscle cells. J Vasc Res 2011, 48:485-494. PMCID: PMC3169366.

Academic Appointments

MaineHealth Institute for Research:

  • Director, Research Training Programs
  • Core Facility Director: Mouse Genome Modification Shared Resource
  • Academy Fellow, Maine Medical Center Institute for Teaching Excellence

Other Appointments:

  • Professor, Department of Medicine, Tufts University School of Medicine, Member, Program in Cell, Molecular, and Developmental Biology at Tufts Graduate School of Biomedical Sciences
  • Graduate Faculty, University of Maine Graduate School of Biomedical Science and Engineering
  • Adjunct Faculty, Department of Biological Sciences, University of Southern Maine

Professional Activities

  • Fellow of the American Heart Association
  • Chair, External Advisory Committee, Maine INBRE
  • Editorial Board, Arteriosclerosis, Thrombosis, Vascular Biology
  • Ad hoc reviewer for NIH: NHLBI, NIGMS, American Heart Association