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
Division of Inflammation Biology

Overview

Our research is focused on understanding how immune cell function is changed during the progression of chronic diseases, particularly atherosclerosis and cancer.

There are 4 main aspects to our research. One is studying how immune cells, such as T cells, are modulated by high cholesterol (such as high LDL-cholesterol) to contribute to atherosclerosis and cancer. We have found that the cholesterol content of Tregs changes their phenotype and function in atherosclerosis. We also found that the cholesterol content of macrophages polarized macrophages to an anti-tumoral phenotype in cancer. The second is to study and target monocytes to aid in the prevention of cancer metastasis. 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 third is to discover new monocyte subsets and understand their regulation of disease. We are using CyTOF mass cytometry to identify new monocyte subsets that may be important in disease. The fourth is to understand how the metabolic and epigenetic profiles of monocytes and their progenitors change during disease progression. This is an exciting new area of research in our program.

From The Lab

Aug 18, 2017

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

Nov 1, 2016

LJI scientists flip molecular switches to distinguish closely related immune cell populations

Nov 19, 2015 // Neurology Advisor

Macrophages, monocytes amplify neuroinflammation in multiple sclerosis

Nov 16, 2015 // Esther Lanhuis- Science Writer

Innate immune cells may prevent metastasis

Nov 2, 2015

The innate immune system modulates the severity of multiple sclerosis

Hedrick Lab

Publications

Arterioscler Thromb Vasc Biol

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

2017-06
Thomas GD, Hamers AAJ, Nakao C, Marcovecchio P, Taylor AM, McSkimming C, Nguyen AT, McNamara CA, Hedrick CC
Science

Hematopoietic stem cells gone rogue

2017-02
Zhu YP, Hedrick CC, Gaddis DE
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
J Clin Invest

ABC transporters and NR4A1 identify a quiescent subset of tissue-resident memory T cells

2016-10
Boddupalli CS, Nair S, Gray SM, Nowyhed HN, Verma R, Gibson JA, Abraham C, Narayan D, Vasquez J, Hedrick CC, Flavell…
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 facotr 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…

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 the Division of Inflammation Biology 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

Amy Blatchley

Research Technician III

Huy Dinh

Instructor

Dalia Gaddis

Postdoctoral Fellow

Biosketch:
I graduated from the School of Pharmacy, Cairo University, Egypt in 2001. In 2010, I obtained a Ph.D. from the University of Alabama at Birmingham in microbiology and immunology. I joined the Hedrick laboratory at La Jolla Institute as a post-doctoral fellow in 2012.

Research Focus:
My research focuses on the role of HDL and its components in regulatory T cell development and function during atherosclerosis progression. I am interested in understanding how cholesterol influence T cell differentiation and development and how manipulating cholesterol levels can influence the balance of the different T cell subsets.

Career Goals:
My goal is to pursue a career in scientific research focusing on the role of T cells in obesity, type II diabetes and heart diseases.

Anouk Hamers

Postdoctoral Fellow

Biosketch:
Anouk obtained her M.S. in Biomedical Sciences in 2008 at the UMC St. Radboud University Nijmegen in The Netherlands. In April 2009 Anouk started her PhD research on “the role of Nuclear receptor Nur77 during inflammation” at the department of Medical Biochemistry of the Academic Medical Center (AMC) Amsterdam in The Netherlands under the supervision of Prof. Carlie JM de Vries and received her degree in February 2015. In January 2014, while finishing her thesis, she started a Postdoctoral fellowship in the lab of Prof Erik SG Stroes at the Department of Experimental Vascular Medicine of the AMC studying macrophage-targeted nano-delivery of therapeutic compounds to the atherosclerotic plaque. Anouk joined the Hedrick laboratory at the La Jolla Institute for Allergy and Immunology in August 2015 as a Postdoctoral fellow.

Research Focus:
Her research focuses on monocyte heterogeneity in health and disease. A technical focus is CyTOF mass cytometry, which uses heavy metal-conjugated antibodies in tandem with time of flight mass spectrometry to measure protein abundances at a single cell resolution.

Career Goals:
She plans to pursue a career in academic research in the fields of Immunology and Cardiovascular Disease.

Erin Johnson

Lab Assistant

Currently, I am a fourth year B.S. Human Biology candidate at the University of California San Diego. In addition, I am also working towards a certificate in Drug Discovery and Development. I joined the Hedrick lab in June 2016 as a student intern, and now I work as a lab assistant on various projects. My research includes examining how myeloid cells change expression and phenotype in response to diseases in mice and humans. I plan to attend medical school after finishing my B.S., with a specialty in pediatric oncology. Also, I have a special interest in cancer research, including understanding the role of the immune system in the tumor microenvironment. I hope to have the opportunity to continue working on these topics in the future.

Paola Marchovecchio

Graduate Student

Biosketch:
Paola graduated from UCLA with a BS in Microbiology, Immunology and Molecular Genetics. She then received her MA in Biomedical Sciences from Boston University and is currently a UCSD graduate student in the Hedrick lab at The La Jolla Institute studying nonclassical monocytes during atherogenesis.

Elsa Molina

Postdoctoral Fellow

Biosketch:
Elsa received her B.S. in Biology from University of Limoges and her M.S. in Molecular Cell Biology and Pathology from University of Poitiers in France in 2011 and 2012, respectively. In 2016, Elsa obtained her Ph.D. in Biomedical Sciences from Federation University in Australia in the laboratory of Prof. Fadi Charchar where her research focused on novel Y chromosome-linked long non-coding RNAs and coronary artery disease in men. During her Ph.D., Elsa also completed the EMBL Australia Ph.D. Course at the University of Melbourne in 2013. Elsa joined the Hedrick laboratory at La Jolla Institute for Allergy and Immunology as a Postdoctoral Fellow in November 2016.

Research Focus:
Elsa’s research focuses on the transcriptional regulation of monocyte subsets in health and disease. She is especially interested by the role of the long non-coding RNAs in these cells.

Career Goals:
Passionate about non-coding RNA biology and cardiovascular research, Elsa wishes to pursue a career in scientific research focusing on the role of non-coding genes in cardiovascular diseases.

Catherine Nakao

Research Tech I

Biosketch:
Catherine received her B.S. in Human Biology from University of California, San Diego in 2016. After graduation, she joined the Hedrick lab as a research intern focusing on monocyte subsets in various strains of mice. In October 2016, she accepted her current position as a research technician.

Research Focus:
While assisting others in their research, she works on her own projects investigating nonclassical monocytes in mouse strain of interest.

Career Goals:
She hopes to continue her work in the immunology field to help move research forward.

Prakash Narasimhan

Postdoctoral Fellow

Claire Olingy

Postdoctoral Fellow

Lindsey Padgett

Postdoctoral Fellow

Sophie Reynolds

Intern

Eric Tran

Intern

Runpei (Amy) Wu

Research Technician III

Debbie 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 Allergy and 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

Epigenetic programming of monocytes in atherosclerosis

Metabolic changes in monocytes during atherosclerosis progression and regression

Regulation of tumor metastasis by nonclassical monocytes

Epigenetic regulation of monocyte development in bone marrow

Regulation of Treg function in the artery wall by high density lipoproteins (HDL)