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.
From left: Chenhao Yang, Larisa Ryzhova, Samantha White, Ashley Soucy, Lucy Liaw, Katie Stieber, Bethany Fortier, Penny Clum, Kimberly Malka, Jackie Turner, Anne Harrington, Jessica Davis-Knowlton
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
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!
Dylan Blackington, BS
Research Assistant III
I am a graduate from the University of New Haven with a BS in Genetics and Biotechnology. As a member of Liaw Lab, I work closely with Larisa Ryzhova as a Research Assistant III. Together we investigate strains selected for the Mouse Genome Project by amplifying and purifying DNA sequences.
Jessica Davis-Knowlton, PhD
My thesis work in the Liaw Lab focused on the role of smooth-muscle cell (SMC) Notch signaling in atherogenesis. In healthy SMC, activation of Notch2 reduces proliferation and may increase contractile protein and activation of Notch3 increases contractile protein. Utilizing primary SMC explants derived from tissue removed from carotid and femoral endarterectomy procedures performed by the Maine Medical Center Vascular Surgery group, we found that they do not respond to activation of the Notch pathway in the same way as healthy SMC. Although atherosclerotic SMC still show reduced proliferation in response to Notch activation, they no longer up-regulate contractile smooth-muscle actin. I am further investigating this observation by comparing plaque burden and composition when SMC Notch2 is absent using mouse models of atherogenesis as a research fellow. Learn more about Jessica’s research.
Bethany Fortier, BS
My research strives to characterize phenotypic changes in perivascular adipose tissue (PVAT) under conditions of dietary methionine restriction that may directly regulate vascular physiology through alteration of signaling. I am particularly focused on its ability to convert PVAT to a more metabolically healthy phenotype despite a high fat diet, and its implications for obesity and cardiovascular disease.
Anne Harrington, BS
Kimberly Malka, MD, PhD
Larisa Ryzhova, MD, PhD
Ashley Soucy, BS
Katie Stieber, BS
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.
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
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
The Liaw Lab members designed their own avatar based on their research and then teamed up to design Dr. Liaw’s avatar. The result: a Liaw Lab Group Emoji!
Liaw Lab Alumni
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, Maine Medical Center Research Institute
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
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 Maine Medical Center Research Institute. 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.
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, in press.
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.
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.
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 [available 4/1/2014]
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
Maine Medical Center Research Institute:
- Director, Research Training Programs
- Core Facility Director: Mouse Genome Modification Shared Resource
- Academy Fellow, Maine Medical Center Institute for Teaching Excellence
- 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
- 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