Click here to learn about Academy events, publications and initiatives around COVID-19.

We are experiencing intermittent technical difficulties. At this time, you may not be able to log in, register for an event, or make a donation via the website. We appreciate your patience, and apologize for any inconvenience this may cause.

Support The World's Smartest Network
×

Help the New York Academy of Sciences bring late-breaking scientific information about the COVID-19 pandemic to global audiences. Please make a tax-deductible gift today.

DONATE
This site uses cookies.
Learn more.

×

This website uses cookies. Some of the cookies we use are essential for parts of the website to operate while others offer you a better browsing experience. You give us your permission to use cookies, by continuing to use our website after you have received the cookie notification. To find out more about cookies on this website and how to change your cookie settings, see our Privacy policy and Terms of Use.

We encourage you to learn more about cookies on our site in our Privacy policy and Terms of Use.

eBriefing

Immune-Stromal Cell Interactions in Fibrosis, Cancer, and Beyond

Immune-Stromal Cell Interactions in Fibrosis, Cancer, and Beyond
Reported by
Sara Donnelly

Posted September 09, 2020

Presented By

Biochemical Pharmacology Discussion Group

The New York Academy of Sciences

The stromal microenvironment plays critical roles in tissue homeostasis, wound healing and the inflammatory response. Comprised of fibroblasts, the extracellular matrix, endothelial cells, pericytes, and adipocytes — many elements of the stroma have recently been implicated as important modulators of the shape and intensity of local immune responses. Thus, greater knowledge of the interactions between immune cells and stromal components is critical to understand their roles in both normal and pathological scenarios.

This eBriefing contains the proceeding of the virtual symposium Immune-Stromal Cell Interactions in Wound Healing, Fibrosis and Cancer, which took place on June 9, 2020. The meeting featured discussion of the common mechanisms of reciprocal regulation between stromal constituents and immune cells that may present exciting new therapeutic targets for a variety of diseases including cancer, fibrosis and chronic inflammatory and autoimmune conditions.

In this eBriefing, You’ll Learn:

  • The importance of immune-stromal interactions in both healthy and diseased tissues
  • Key mechanisms governing reciprocal interactions between immune cells and stromal constituents
  • Potential therapeutic targets that present new opportunities for the development of effective drugs for widespread human diseases

Speakers

Ellen Puré, PhD
Ellen Puré, PhD

University of Pennsylvania School of Veterinary Medicine

Edna Cukierman, PhD
Edna Cukierman, PhD

Fox Chase Cancer Center

Laura Donlin, PhD
Laura Donlin, PhD

HSS Research Institute

Carolin Koss
Carolin K. Koss

Boehringer Ingelheim; University of Konstanz

Ari Molofsky
Ari Molofsky, MD, PhD

University of California, San Francisco

David Lagares, PhD
David Lagares, PhD

Harvard Medical School

Laura Santambrogio
Laura Santambrogio, MD, PhD

Weill Cornell Medical College

Michael L. Whitfield, PhD
Michael L. Whitfield, PhD

Geisel School of Medicine at Dartmouth

Key Role for Cancer-Associated Fibroblasts

Speakers

Ellen Puré, PhD (Keynote)
University of Pennsylvania School of Veterinary Medicine

Dr. Ellen Puré is the Grace Lansing Lambert Professor of Biomedical Science and Chair, Department of Biomedical Sciences, at the University of Pennsylvania School of Veterinary Medicine in Philadelphia, PA. Her research focuses on the cellular and molecular basis of inflammation and fibrosis. She studies the basic mechanisms involved in these processes and the contribution of these processes to disease, with a particular emphasis on cancer. A major focus of her laboratory’s work is to define the role of stromal cells, extracellular matrix (ECM), and matrix remodeling in cancer initiation, progression, and metastasis; and on developing novel therapeutic approaches that target stromal cell-dependent pathways to use in combination with more conventional cancer therapies that target malignant cells, anti-angiogenic therapies, and immune modulators. Her lab uses genetic, pharmacologic, biochemical, and advanced imaging approaches to study the role of stroma in mouse models of desmoplastic solid epithelial cell-derived tumors (i.e., carcinomas), including pancreatic, breast, and lung cancers. In addition to her research program, Dr. Puré serves as the director of the Penn Vet Cancer Center. Dr. Puré received her PhD from the University of Texas Southwestern Medical School and was a postdoctoral researcher and Assistant Professor at The Rockefeller University before joining the University of Pennsylvania faculty.

Ellen Puré (University of Pennsylvania School of Veterinary Medicine)

Edna Cukierman, PhD
Fox Chase Cancer Center

Born and raised in Mexico City, Edna (Eti) Cukierman immigrated to Israel in 1986 and earned her doctoral degree from the Technion-Israel Institute of Technology in 1997.

Her research in extracellular matrix (ECM) biology began with a Postdoctoral Fellowship from 1997 through 2002 at the National Institute of Dental and Craniofacial Research at the National Institutes of Health. It was during this time that a system she developed rendered, for the first time, a multilayered fibroblastic cell-derived ECM (known as CDM), which she used to discover the physiological “3D-matrix adhesion” formed between fibroblasts and ECM. Today, CDMs are broadly used in research, as they allow long-term culture of single and mixed cell populations while mimicking discrete in vivo niches.

Dr. Cukierman joined the Fox Chase Cancer Center Faculty in 2002. Her research focuses on defining critical roles of stromal cells (mostly fibroblasts, but also immune cells and nerves) in generating ECM-dependent signals that promote and constrain tumor growth; and reciprocally on understanding how signals from tumor cells and the ECM condition features of the stroma. While her independent work involves cell biological and bioengineering approaches to science, she also co-leads the Multidisciplinary Pancreatic Cancer Institute and co-directs the Immune Monitoring Facility at Fox Chase, which supports clinical operations.

Edna Cukierman (Fox Chase Cancer Center)

Further Readings

Puré

Avery D, Govindaraju P, Jacob M, et al.

Matrix Biol. 2018;67:90-106

Barrett R, Puré E

[published online ahead of print, 2020 May 10]. Curr Opin Immunol. 2020;64:80-87

Cukierman

Franco-Barraza J, Raghavan KS, Luong T, Cukierman E

Methods Cell Biol. 2020;156:109-160

Macrophage-Dependent Signaling in Autoimmune Diseases and Fibrosis

Speakers

Laura Donlin, PhD
HSS Research Institute

Dr. Laura Donlin aims to deepen our understanding of autoimmune and musculoskeletal disorders by uncovering molecular patterns found within patient samples. The goal of this work is to create personalized treatment strategies based on patient-specific molecular signatures.

Working closely with Hospital for Special Surgery (HSS) rheumatologists and surgeons, Dr. Donlin analyzes patient samples with cutting-edge molecular techniques such as next-generation sequencing. Combining these functional genomics analyses with drug response assays, Dr. Donlin looks to understand how the cellular and molecular profiles found within patient samples relate to treatment responses. Dr. Donlin and colleagues also use cell culture models to study how cells co-evolve during chronic inflammatory responses, with the intent of identifying novel therapeutic targets for autoimmune conditions such as rheumatoid arthritis.

Dr. Donlin received her PhD from Columbia University and was a postdoctoral researcher at The Rockefeller University, prior to joining HSS.

Laura Donlin (HSS Research Institute)

Carolin K. Koss
Boehringer Ingelheim; University of Konstanz

Born in Esslingen, Germany, Carolin Koss received her bachelor's degree in chemistry and biochemistry from the University of Munich, Germany (LMU), and continued her studies at the University of Regensburg, Germany, to receive her master's degree in medicinal chemistry. She conducted her master's thesis in the lab of Professor Matthias Senge at the Trinity College in Dublin, Ireland. In 2018, Dr. Koss joined the laboratory of Karim El Kasmi in the department of immunology and respiratory at Boehringer Ingelheim in Biberach, Germany, to receive her PhD in cooperation with the University of Constance under the supervision of Professor Florian Gantner. Her main goal is to identify and functionally characterize the pro-fibrotic macrophage phenotypes. Dr. Koss studies the intercellular communication between macrophages, fibroblasts, and epithelial cells using in vivo, ex vivo, and in vitro systems with cells derived from mice and lung fibrosis patients. The implication of her work is to provide a starting point for therapeutic target discovery in the search for cures of fibrosing diseases.

Carolin K. Koss (Boehringer Ingelheim; University of Konstanz)

Further Readings

Donlin

Kuo D, Ding J, Cohn IS, et al

Sci Transl Med. 2019;11(491):eaau8587

Tissue Regeneration and Type II Immune Responses in Inflammation

Speakers

Ari Molofsky, MD, PhD
University of California, San Francisco 

Ari Molofsky grew up in Austin, Texas, and received his undergraduate degree in Molecular Biology from the University of Texas, followed by an MD/PhD from the University of Michigan as part of the Medical Scientist Training Program (MSTP). His graduate work in the lab of Michele Swanson focused on the regulation of bacterial virulence and macrophage cytoplasmic response. His postdoctoral fellowship in the lab of Richard Locksley examined the regulation and function of group 2 innate lymphoid cells (ILC2s), where he helped define the role of ILC2s in systemic metabolism and described the coordinate positive and negative regulation of ILC2s and regulatory T cells (Tregs) via the cytokines IL-33 and IFNg. Dr. Molofsky established his lab in July 2015 and studies the regulation and niches of tissue-resident lymphocytes, including ILC2s and Treg subsets. His group is particularly interested in how tissue resident lymphocytes cross-talk with stromal cells to initiate beneficial and pathologic immunity and has recently defined an adventitial ILC2 niche in multiple tissues, including lung, adipose tissue, and brain meninges.

In addition to his research, Dr. Molofsky practice medicine part-time as an attending hematopathologist with a particular focus on clinical flow cytometry. He is also engaged in teaching at multiple levels, including pathology residents and fellows, medical students, graduate students, and dental students. Dr. Molofsky is the assistant director of the UCSF medical school Pathogens and Host Defense course, with a focus on immunology teaching and co-director of a Biomedical Sciences (BMS) mini-course that provides a ‘deep-dive’ on tissue-resident immunity.

Ari Molofsky (University of California, San Francisco)

David Lagares, PhD
Harvard Medical School

David Lagares, PhD, is an Assistant Professor of Medicine at Harvard Medical School and a Principal Investigator at the Center for Immunology and Inflammatory Diseases and the Division of Pulmonary Critical Care Medicine at the Massachusetts General Hospital. His research laboratory investigates cellular and molecular mechanisms that regulate the delicate balance between organ regeneration and fibrosis following tissue injury, with an emphasis on the biochemical and biomechanical drivers of myofibroblast recruitment and activation.

Ultimately, his research laboratory seeks to develop novel anti-fibrotic therapies for the treatment of human diseases such as idiopathic pulmonary fibrosis, systemic sclerosis, liver cirrhosis, progressive kidney disease, and desmoplastic tumors. Seminal work from his laboratory includes the identification of the ADAM10-sEphrin-B2 pathway in lung injury and fibrosis and the use of BH3 mimetic drugs to induce myofibroblast apoptosis and reversion of established fibrosis in the autoimmune fibrotic disease of scleroderma. His research has been published in journals such as Nature Medicine and Science Translational Medicine. He is a recipient of multiple career awards from the National Institutes of Health and the American Thoracic Society. He is also a cofounder of Mediar Therapeutics and Zenon Biotech, biotech companies developing innovative anti-fibrotic therapies.

David Lagares (Harvard Medical School)

Further Readings

Molofsky

Dahlgren MW, Jones SW, Cautivo KM, et al

Immunity. 2019;50(3):707-722.e6. doi:10.1016/j.immuni.2019.02.002

Lagares

Tschumperlin DJ, Lagares D

Pharmacol Ther. 2020;212:107575

New Tools for Probing the Molecular Basis of Disease

Speakers

Laura Santambrogio, MD, PhD
Weill Cornell Medical College

Laura Santambrogio, MD, PhD, is the Associate Director for Precision Immunology at the Englander Institute for Precision Medicine. She also holds appointments as Professor of Radiation Oncology, and Professor of Physiology and Biophysics at Weill Cornell Medicine. Dr. Santambrogio studies the mechanisms of antigen processing and presentation, peptide binding to MHC class II molecules and the overall role of dendritic cells in innate and adaptive immune responses, which has been the focus of her laboratory since her time at Harvard, and her field of research for a number of years. She believes that learning the basic mechanisms of the MHC antigen processing and presentation machinery is important towards our understanding of immune responses, from physiology to pathology. Similarly, learning how to build an immune response to a pathogen, which self-peptides are presented in autoimmunity, and how you select immunogenic peptides for cancer immunotherapy, are very important.

Laura Santambrogio (Weill Cornell Medical College)

Michael L. Whitfield, PhD
Geisel School of Medicine at Dartmouth

Dr. Whitfield is Professor and Chair of the Department of Biomedical Data Science at the Geisel School of Medicine. He is the founder and Director of the Center for Quantitative Biology, Co-Director of the Burroughs Wellcome Big Data in the Life Sciences Training Program, and is a Scientific Founder of Celdara Medical, LLC. Dr. Whitfield graduated with honors from North Carolina State University with degrees in biochemistry and chemistry. He received his PhD from the University of North Carolina, Chapel Hill in Biochemistry and Biophysics, and then performed postdoctoral training in genetics, genomics, and bioinformatics at Stanford University School of Medicine. Dr. Whitfield joined the faculty at Dartmouth's Geisel School of Medicine in 2003. The American Society for Cell Biology awarded Dr. Whitfield the 2002 Paper of the Year for Cell Biology (Whitfield et al. 2002 MBC). He was a V Scholar for Cancer Research, was named a Hulda Irene Duggan Arthritis Investigator, and is the recipient of multiple private foundation and NIH grants.

The Whitfield lab uses genomic and computational approaches to identify the molecular basis of autoimmunity and fibrosis with an emphasis on systemic sclerosis (SSc). They identified the first molecular subsets in an autoimmune disease, similar to those that have now been well studied in cancer. His group uses bulk and single cell sequencing methods to understand genetic, epigenetic, and gene-gene networks that drive fibrosis. His group has used statistical and machine learning approaches to develop classifiers that break down patient heterogeneity, which are now used for precision medicine in SSc clinical trials.

Michael L. Whitfield (Geisel School of Medicine at Dartmouth)

Further Readings

Santambrogio

Clement CC, Wang W, Dzieciatkowska M, et al

Sci Rep. 2018;8(1):11253. Published 2018 Jul 26

Whitfield