Hedrick Lab

Hedrick Lab

"My interest in science began when I was a child, as my mother suffered from complications of Type 1 diabetes, and so when I was little, I always wanted to study it. Later, I became interested in cardiovascular disease, which is also a complication of diabetes, as a global health concern. I hope my work at the la Jolla Institute will bring new opportunities to find therapies to reduce or prevent atherosclerosis development." — Catherine “Lynn” Hedrick, Ph.D. // Professor

Overview

There are 3 main areas of research in the lab. A primary goal in the laboratory is to study and target monocytes to aid in the prevention of cancer. Some monocytes are pro-tumoral, and other monocyte subsets are anti-tumoral, as we have shown that nonclassical monocytes prevent tumor metastasis. We want to understand more about how these monocyte subsets impact cancer initiation and progression. The second research goal is to study neutrophil heterogeneity in cancer and cardiovascular disease. We use high dimensional methods including CyTOF mass cytometry and single cell RNA-Sequencing to identify new myeloid cell and T cell subsets that may be important in cardiovascular disease and cancer. We wish to determine how these immune cells phenotypically and functionally change, and how they interact in the microenvironments of the atherosclerotic plaque and the tumor. We can compare and contrast these immune cell interactions in these two diseases to identify effective new combination immunotherapies.

From The Lab

Oct 27, 2020

Lynn Hedrick receives more than $500,000 for COVID-19 research

New immune cell studies may shed light on heart attacks, inflammation seen in COVID-19 patients
Aug 18, 2020 // Cell

LJI team gets first-ever look at a rare but vital stem cell in humans

New understanding of immune cell origins may offer cancer and COVID-19 drug targets
Aug 28, 2018 // Cell Reports

Researchers find elusive source of most abundant immune cell

Discovery of human neutrophil progenitor opens the door for new therapeutic targets and could serve as an important biomarker for early cancer detection
Mar 15, 2018 // Nature Communications

Western diet depletes artery-protecting immune cells

La Jolla Institute scientists show how immune cells that shield arteries from inflammation are reprogrammed into cells that promote inflammation by high levels of fats and cholesterol
Aug 18, 2017

LJI researcher lands $13 million federal research grant to study heart disease

The multi-institutional effort led by Dr. Catherine Hedrick will explore the role of immune cells in cardiovascular disease; identify novel immune-based therapeutic strategies

Hedrick Lab

Publications

Nat Commun

Perivascular Localization of Macrophages in the Intestinal Mucosa Is Regulated by Nr4a1 and the Microbiome

2020-03
Honda M, Surewaard BGJ, Watanabe M, Hedrick CC, Lee WY, Brown K, McCoy KD, Kubes P.
J Immunol

Patrolling Monocytes Control NK Cell Expression of Activating and Stimulatory Receptors to Curtail Lung Metastases

2020-01
Narasimhan PB, Eggert T, Zhu YP, Marcovecchio P, Meyer MA, Wu R, Hedrick CC
Journal of Immunology

Neuropilin-1 expression on CD4 T cells is atherogenic and facilitates T cell migration to the aorta in atherosclerosis

2019-12
Gaddis DE, Padgett LE, Wu R, Hedrick CC
bioRxiv

Lack of apolipoprotein A1 impairs optimal regulatory T cell homeostasis at steady state due to impaired IL-2 signaling

2019-09
Gaddis DE, Wu R, Parks JS, Sorci-Thomas MG, Hedrick CC
J Leukoc Biol

Monocyte heterogeneity and functions in cancer

2019-08
Olingy CE, Dinh HQ, Hedrick CC
J Vis Exp

Preparation of whole bone marrow for mass cytometry analysis of neutrophil-lineage cells

2019-06
Zhu YP, Padgett L, Dinh HQ, Marcovecchio P, Wu R, Hinz D, Kim C, Hedrick CC
Annu Rev Immunol

Nonclassical monocytes in health and disease

2019-04
Narasimhan PB, Marcovecchio P, Hamers AAJ, Hedrick CC
Annu Rev Immunol

Nonclassical monocytes in health and disease

2019-04
Narasimhan PB, Marcovecchio P, Hamers AAJ, Hedrick CC
J Leukoc Biol

Monocyte heterogeneity and functions in cancer

2019-02
Olingy CE, Dinh HQ, Hedrick CC
Arterioscler Thromb Vasc Biol

Human monocyte heterogeneity as revealed by high-dimensional mass cytometry

2019-01
Hamers AAJ, Dinh HQ, Thomas GD, Marcovecchio P, Blatchley A, Nakao CS, Kim C, McSkimming C, Taylor AM, Nguyen AT,…
Sci Immunol

Neutrophils: New insights and open questions

2018-12
Ley K, Hoffman HM, Kubes P, Cassatella MA, Zychlinsky A, Hedrick CC, Catz SD
Cell Rep

Identification of an early unipotent neutrophil progenitor with pro-tumoral activity in mouse and human bone marrow

2018-08
Zhu YP, Padgett L, Dinh HQ, Marcovecchio P, Blatchley A, Wu R, Ehinger E, Kim C, Mikulski Z, Seumois G, Madrigal A,…
Circ Res

Atlas of the immune cell repertoire in mouse atherosclerosis defined by single-cell RNA-sequencing and mass cytometry

2018-06
Winkels H, Ehinger E, Vassallo M, Buscher K, Dinh HQ, Kobiyama K, Hamers AAJ, Cochain C, Vafadarnejad E, Saliba AE,…
Nat Med

Understanding the tumor immune microenvironment (TIME) for effective therapy

2018-05
Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M, Coussens LM, Gabrilovich DI, Ostrand-Rosenberg S,…
Nat Commun

Apolipoprotein AI prevents regulatory to follicular helper T cell switching during atherosclerosis

2018-03
Dalia Gaddis D, Lindsey Padgett L, Runpei Wu R, Chantel McSkimming C, Romines V, Taylor A, McNamara C, Kronenberg M,…
Front Cardiovasc Med

Patrolling mechanics of non-classical monocytes in vascular inflammation

2017-12
Buscher K, Marcovecchio P, Hedrick CC, Ley K
Arterioscler Thromb Vasc Biol

Scavenger receptor CD36 directs nonclassical monocyte patrolling along the endothelium during early atherogenesis

2017-09
Marcovecchio PM, Thomas GD, Mikulski Z, Ehinger E, Mueller KAL, Blatchley A, Wu R, Miller YI, Nguyen AT, Taylor AM,…
Arterioscler Thromb Vasc Biol

Human blood monocyte subsets: a new gating strategy defined using cell surface markers identified by mass cytometry

2017-08
Thomas GD, Hamers AAJ, Nakao C, Marcovecchio P, Taylor AM, McSkimming C, Nguyen AT, McNamara CA, Hedrick CC
Sci Rep

ATP binding cassette transporter ABCA7 regulates NKT cell development and function by controlling CD1d expression and lipid raft content

2017-01
Nowyhead HN, Chandra S, Kiosses W, Marcovecchio P, Andary F, Zhao M, Fitzgerald ML, Kronenberg M, Hedrick CC
Arterioscler Thromb Vasc Biol

Transcriptional control of monocyte development

2016-09
Zhu YP, Thomas GD, Hedrick CC
J Clin Invest

Loss of ABCG1 influences regulatory T cell differentiation and atherosclerosis

2016-09
Cheng HY, Gaddis DE, Wu R, McSkimming C, Haynes LD, Taylor AM, McNamara CA, Sorci-Thomas M, Hedrick CC
Nature Immunology

Transcription factor Nr4a1 couples sympathetic and inflammatory cues in CNS-recruited macrophages to limit neuroinflammation

2015-12
Shaked I, Hanna , Shaked H, Chodaczek G, Nowyhed HN, Tweet G, Tacke R, Basat AB, Mikulski Z, Togher S, Miller J,…
Science

Patrolling monocytes control tumor metastasis to the lung

2015-11
Hanna RN, Cekic C, Sag D, Tacke R, Thomas GD, Nowyhed H, Herrley E, Rasquinha N, McArdle S, Wu R, Peluso E, Metzger D,…
Journal of Immunology

Cutting edge: the orphan nuclear receptor Nr4a1 regulates CD8+ T cell expansion and effector function through direct repression of Irf4

2015-10
Nowyhed HN, Huynh TR, Thomas GD, Blatchley Q, Hedrick CC
Journal of Immunology

Cardif (MAVS) regulates the maturation of NK cells

2015-09
Haynes LD, Verma S, McDonald B, Wu R, Tacke R,Nowyhed HN, Ekstein J, Feuvrier A, Benedict CA, Hedrick CC
Scientific Reports

The transcription factor NR4A1 is essential for the development of a novel macrophage subset in the thymus

2015-06
Tacke R, Hilgendorf I, Garner H, Waterborg C, Park K, Nowyhed H, Hanna RN, Wu R, Swirski FK, Geissmann F, Hedrick CC
Arteriosclerosis Thrombosis and Vascular Biology

Nonclassical patrolling monocyte function in the vasculature

2015-06
Thomas G, Tacke R, Hedrick CC, Hanna RN
Journal of Experimental Medicine

Monocyte phenotypes: when local education counts

2015-04
Quintar AA, Hedrick CC, Ley K
Scientific Reports

The nuclear receptor nr4a1 controls CD8 T cell development through transcriptional suppression of runx3

2015-03
Nowyhed HN, Huynh TR, Blatchley A, Wu R, Thomas GD, Hedrick CC
Arteriosclerosis Thrombosis and Vascular Biology

Lymphocytes in atherosclerosis

2015-02
Hedrick CC
Nature Communications

The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity

2015-02
Sag D, Cekic C, Wu R, Linden J, Hedrick CC
Journal of Clinical Investigation

IL-10-producing NKT10 cells are a distinct regulatory invariant NKT cell subset

2014-09
Sag D, Krause P, Hedrick CC, Kronenberg M, Wingender G
Nature Medicine

Stressing out stem cells: linking stress and hematopoiesis in cardiovascular disease

2014-07
Hanna RN, Hedrick CC
Atherosclerosis

Gammadelta (ϒδ) T lymphocytes do not impact the development of early atheroscherosis

2014-06
Cheng HY, Wu R, Hedrick CC
Circulation Research

Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in infarcted myocardium

2014-05
Hilgendorf I, Gerhardt L, Tan TC, Winter C, Holderried TA, Chousterman BG, Iwamoto Y, Liao R, Zirlik A,…
Current Opinion in Lipidology

NR4A nuclear receptors in immunity and atherosclerosis

2013-10
Hamers AA, Hanna RN, Nowyhed H, Hedrick CC, de Vries CJ
Current Opinion in Lipidology

Myeloid cells in atherosclerosis: a delicate balance of anti-inflammatory and proinflammatory mechanisms

2013-10
Koltslova EK, Hedrick CC, Ley K
PLoS One

Increased cholesterol content in gammadelta (γδ) T lymphocytes differentially reguates their activationIncreased cholesterol content in gammadelta (γδ) T lymphocytes differentially reguates their activation

2013-05
Cheng HY, Wu R, Gegre AK, Hanna RN, Smith DJ, Parks JS, Ley K, Hedrick CC
Cell

Nr4a1-dependent Ly6C(low) monocytes monitor endothelial cells and orchestrate their disposal

2013-04
Carlin LM, Stamatiades EG, Auffray C, Hanna RN, Glover L, Vizcay-Barrena G, Hedrick CC, Cook HT, Diebold S, Geissmann F
Circulation

Molecular imaging of the paracrine proangiogenic effects of progenitor cell therapy in limb ischemia

2013-02
Ryu JC, Davison BP, Xie A, Qi Y, Zha D, Belcik JT, Caplan ES, Woda JM, Hedrick CC, Hanna RN, Lehman N, Zhao Y, Ting A,…
Journal of Immunology

ATP-binding cassette transporter G1 intrinsically regulates invariant NKT cell development

2012-12
Sag D, Wingender G, Nowyhed H, Wu R, Gebre AK, Parks JS, Kronenberg M, Hedrick CC
Arteriosclerosis Thrombosis and Vascular Biology

Accelerated atherosclerosis in apoe-/- mice heterozygous for the insulin receptor and the insulin receptor substrate-1

2012-02
Galkina EV, Butcher M, Keller SR, Goff M, Bruce A, Pei H, Sarembock IJ, Sanders JM, Nagelin MH, Srinivasan S, Kulkarni…
Circulation Research

NR4A1 (Nur77) deletion polarizes macrophages toward an inflammatory phenotype and increases atherosclerosis

2012-02
Hanna RN, Shaked I, Hubbeling HG, Punt JA, Wu R, Herrley E, Zaugg C, Pei H, Geissmann F, Ley K, Hedrick CC
Arteriosclerosis Thrombosis and Vascular Biology

Monocyte and macrophage dynamics during atherogenesis

2011-07
Ley K, Miller YI, Hedrick CC
Nature Immunology

The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C(-) monocytes

2011-07
Hanna RN, Carlin LM, Hubbeling HG, Nackiewicz D, Green AM, Punt JA, Geissmann F, Hedrick CC
Diabetes

Links between insulin resistance, adenosine A2B receptors, and inflammatory markers in mice and humans

2011-02
Figler RA, Wang G, Srinivasan S, Jung DY, Zhang Z, Pankow JS, Ravid K, Fredholm B, Hedrick CC, Rich SS, Kim JK, Lanoe…
J Clin Invest

An intracellular role for ABCG1-mediated cholesterol transport in the regulated secretory pathway of mouse pancreatic beta cells

2010-07
Sturek JM, Castle JD, Trace AP, Page LC, Castle AM, Evans-Molina C, Parks JS, Mirmira RG, Hedrick CC
Arterioscler Thromb Vasc Biol

ABCG1 deficiency in mice promotes endothelial activation and monocyte-endothelial interactions

2010-04
Whetzel AM, Sturek JM, Nagelin MH, Bolick DT, Gebre AK, Parks JS, Bruce AC, Skaflen MD, Hedrick CC
J Immunol

ATP-binding cassette transporter G1 negatively regulates thymocyte and peripheral lymphocyte proliferation

2010-01
Armstrong AJ, Gebre AK, Parks JS, Hedrick CC
Mediators Inflammation

Human lipoxygenase pathway gene variation and association with markers of subclinical atherosclerosis in the diabetes heart study

2010-01
Burdon KP, Rudock ME, Lehtinen AB, Langefeld CD, Bowden DW, Register TC, Liu Y, Freedman BI, Carr JJ, Hedrick CC, Rich…

Principal Investigator

Catherine “Lynn” Hedrick, Ph.D.

Professor

Hedrick received her B.S. in Biology from Salem College in Winston-Salem, North Carolina in 1984. She received her Ph.D. in Biochemistry from Wake Forest University School of Medicine in 1992, where she performed her graduate research on LDL cholesterol metabolism in the laboratory of Dr Lawrence Rudel. From 1992 to 1995, she performed her postdoctoral research on HDL metabolism in the laboratory of Dr Aldons ‘Jake’ Lusis at UCLA. From 1995 to 1999, she worked as a junior faculty member in the Division of Cardiology at UCLA, where her research focused on inflammation and endothelial function. From 2000 to 2009, Dr. Hedrick worked as a professor in the Departments of Pharmacology, Medicine, and Molecular Physiology and Biological Physics at the University of Virginia in Charlottesville. In 2009, Dr. Hedrick was awarded the Harrison Chair of Molecular Physiology and Biological Physics at the University of Virginia. Dr. Hedrick joined the faculty of LJI in 2009.

Dr. Hedrick currently serves on the NHLBI Vascular Cellular Molecular Biology Review Committee, the AAI Committee for the Status of Women, and the American Heart Association ATVB Council Leadership Committee. She is also a Fellow of the American Heart Association. Recent honors received by Dr. Hedrick include the ATVB Vascular Biology Special Recognition Award, from the American Heart Association in 2013; the Jeffrey M. Hoeg Arteriosclerosis Thrombosis and Vascular Biology Award for Basic Science and Clinical Research from the American Heart Association in 2014; and the Arteriosclerosis Thrombosis and Vascular Biology Mentor of Women Award from the American Heart Association in 2015.

Lab Members

Daniel Araujo

Project Manager/Scientific Editor

Sonya Haupt

Rotating Graduate Student

Christine Huh

Postdoc Fellow (0 year)

Melissa Meyer

Postdoctoral Fellow

Biosketch:
I graduated from the University of Minnesota-Twin Cities in December 2011 with a Bachelor of Science degree in Genetics, Cell Biology and Development. I then moved to Washington University in Saint Louis to complete my Ph.D. in Molecular Cell Biology where I studied changes in dendritic cell development during cancer. I have been a postdoctoral fellow in the Hedrick lab at La Jolla Institute for Immunology since June 2018.

Research Interests:
I am interested in the role of myeloid cells in disease, with a focus on neutrophils and monocytes. Neutrophil heterogeneity changes during cancer. I am working to understand the contributions of specific subsets of neutrophils to tumor progression. I’m also working to understand how neutrophil and non-classical monocytes interact, and how these interactions might contribute to disease.

Lindsey Padgett

Postdoctoral Fellow

Eric Tran

Lab Assistant

Runpei (Amy) Wu

Research Technician III

Debbi Yoakum

Research Technician II

Yanfan (Peipei) Zhu

Postdoctoral Fellow

Biosketch:
Peipei received her B.S. degree in Biotechnology from Life Science College, Northwest A & F University, China. She then pursued her Ph.D. study and received M.S. & Ph.D. degree of Immunology & Microbiology from University of Louisville in Kentucky, US in 2010 and 2014, respectively. She started her postdoc training at the Hedrick laboratory in the La Jolla Institute for Immunology in September of 2014.

Research Focus:
Peipei’s current research interest focuses on the hematopoietic stem & progenitor cell (HSPC) development towards myeloid lineage and the mechanism of aberrant myelopoiesis with disease development including cancer and atherosclerosis .

Career Goals:
Peipei is passionately building up her career as professional research investigator to continue unraveling the mystery of aberrant myelopoiesis with the goal of developing new generation of therapeutic method for cancer & cardiovascular disease.

Hedrick Lab

Research Projects

CD8 T cell Functions in Atherosclerosis

Immunoprofiling of human immune cells in cardiovascular disease and cancer

Epigenetic Regulation of Neutrophil and Monocyte Development in Disease.

Regulation of Treg function in cardiovascular disease