The fascinating area of molecular medicine provides a molecular and cellular description of health and disease. Starting with the understanding of gene regulation and epigenetics, i.e., the interplay of transcription factors and chromatin, this book will provide an fundamental basis of nearly all processes in physiology, both in health as well as in most common disorders, such as cancer, diabetes as well as in autoimmune diseases. Most non-communicable human diseases have a genetic (= inherited) as well as an epigenetic component. The later one is based on our lifestyle choices and environmental exposures. Many common diseases, such as type 2 diabetes, can be explained only to some 20% via a genetic predisposition. We cannot change the genes that we are born with but we can take care of the remaining 80% being primarily based on our epigenome. Therefore, there is a high level of individual responsibility for staying healthy. Thus, not only biologists and biochemists should be aware of this topic, but all students of biomedical disciplines will benefit from being introduced into the concepts of molecular medicine. This will provide them with a good basis for their specialized disciplines of modern life science research.
The book is subdivided into 42 chapters that are linked to a series of lecture courses in “Molecular Medicine and Genetics”, “Molecular Immunology”, “Cancer Biology” and “Nutrigenomics” that is given by one of us (C. Carlberg) in different forms since 2002 at the University of Eastern Finland in Kuopio. This book represents an updated version and fusion of the books textbooks “Mechanisms of Gene Regulation: How Science Works” (ISBN 978-3-030-52321-3), “Human Epigenetics: How Science Works” (ISBN 978-3-030-22907-8). “Molecular Immunology: How Science Works” (ISBN 978-3-031-04024-5), “Cancer Biology: How Science Works” (ISBN 978-3-030-75699-4) and “Nutrigenomics: How Science Works” (ISBN 978-3-030-36948-4). By combining basic understanding of cellular mechanism with clinical examples, the authors hope to make this textbook a personal experience. A glossary in the appendix will explain the major specialist’s terms.
Author(s): Carsten Carlberg, Eunike Velleuer, Ferdinand Molnár
Publisher: Springer
Year: 2023
Language: English
Pages: 707
City: Cham
Preface
Contents
Abbreviations
1 The Human Genome and Its Variations
1.1 Migration of Homo Sapiens and the Diversity of Human Populations
1.2 Genetic Variants of the Human Genome
1.3 Measuring Human Genetic Variations
Additional Reading
2 Gene Expression and Chromatin
2.1 Central Dogma of Molecular Biology
2.2 Nucleosomes: Central Units of Chromatin
2.3 Chromatin Structure and Epigenetics
2.4 Epigenetics Enables Gene Expression
2.5 Gene Regulation in the Context of Nuclear Architecture
Additional Reading
3 Basal Transcriptional Machinery
3.1 Core Promoter
3.2 TATA Box and Other Core Promoter Elements
3.3 Genome-Wide Core Promoter Identification
3.4 TFIID and MED as Paradigms of Multiprotein Complexes
Additional Reading
4 Transcription Factors and Signal Transduction
4.1 Site-Specific Transcription Factors and Their Domains
4.2 Classification of Transcription Factors
4.3 Activation of Transcription Factors
4.4 Inflammatory Signaling via NFκB
4.5 Sensing Cellular Stress via P53
Additional Reading
5 A Key Transcription Factor Family: Nuclear Receptors
5.1 The Nuclear Receptor Superfamily
5.2 Molecular Interactions of Nuclear Receptors
5.3 Nuclear Receptors as Nutrient Sensors
5.4 Integration of Lipid Metabolism by PPARs, LXRs and FXR
5.5 Coordination of the Immune Response by VDR
Additional Reading
6 DNA Methylation
6.1 Cytosines and Their Methylation
6.2 The DNA Methylome
6.3 CTCF and Genetic Imprinting
6.4 DNA Methylation and Disease
Additional Reading
7 Histone Modifications
7.1 Histones and Their Modifications
7.2 Genome-Wide Interpretation of the Histone Code
7.3 Chromatin Modifiers
7.4 Gene Regulation via Chromatin Modifiers
Additional Reading
8 Chromatin Remodeling and Organization
8.1 Nucleosome Positioning at Promoters
8.2 Chromatin Remodeling
8.3 Organization of Chromatin in the Nucleus
Additional Reading
9 Regulatory Impact of Non-coding RNA
9.1 Non-Coding RNAs
9.2 miRNAs and Their Regulatory Potential
9.3 Long ncRNAs
9.4 Enhancer RNAs
Additional Reading
10 Genome-Wide Principles of Gene Regulation
10.1 Gene Regulation in the Context of Big Biology
10.2 Epigenetic Methods
10.3 Integrating Epigenome-Wide Datasets
10.4 Genome-Wide Understanding of Epigenetics
Additional Reading
11 Epigenetics in Development
11.1 Epigenetic Changes During Early Human Development
11.2 The Epigenetic Landscape
11.3 Epigenetic Dynamics During Differentiation
11.4 Epigenetics of Blood Cell Differentiation
11.5 Neuronal Development: The Role of Epigenetics
11.6 Epigenetic Basis of Memory
Additional Reading
12 Epigenetics and Aging
12.1 Transgenerational Epigenetic Inheritance
12.2 Population Epigenetics
12.3 Epigenetics of Aging
12.4 Epigenetics of the Circadian Clock
Additional Reading
13 Epigenetics and Disease
13.1 Epigenetic Reprograming in Cancer
13.2 Epigenetic Basis of Neurological Diseases
13.3 Epigenetic Therapy of Diseases
Additional Reading
14 Cells and Tissues of the Immune System
14.1 Global Burden of Infectious Diseases
14.2 Innate and Adaptive Immunity
14.3 Hematopoiesis
14.4 Primary and Secondary Structures of the Immune System
Additional Reading
15 Innate Immunity and Inflammation
15.1 Receptors for PAMPs and DAMPs
15.2 Myeloid and Lymphoid Cells of Innate Immunity
15.3 Role of Epigenetics in Immune Responses
15.4 Mechanisms of Phagocytosis and Inflammation
Additional Reading
16 Adaptive Immunity and Antigen Receptor Diversity
16.1 Classes and Responses of Adaptive Immune Cells
16.2 Lymphocyte Maturation
16.3 Mechanisms of Antigen Receptor Diversity
Additional Reading
17 B Cell Immunity: BCRs, Antibodies and Their Effector Functions
17.1 Structure and Diversity of Antibodies and BCRs
17.2 BCR Signaling
17.3 Humoral Adaptive Immune Response
Additional Reading
18 Antigen-Presenting Cells and MHCs
18.1 Antigen-Presenting Cells
18.2 MHC Proteins and the HLA Locus
18.3 MHC Pathways
Additional Reading
19 T Cell Immunity: TCRs and Their Effector Functions
19.1 TCR Signaling
19.2 T Cell Effector Functions
19.3 TH Cells
19.4 Cytotoxic T Cells
Additional Reading
20 Immunity to Bacterial Pathogens and the Microbiome
20.1 Principles of Immune Responses to Infections
20.2 Immune Responses to Bacteria
20.3 Emerging Microbial Pathogens
20.4 Immunity to the Microbiome
Additional Reading
21 Immunity to Viral Pathogens and the Virome
21.1 Principles of Immune Responses to Viruses
21.2 Chronic Virus Infections and Emerging Viral Pathogens
21.3 Influenza
21.4 COVID-19
Additional Reading
22 Tolerance and Transplantation Immunology
22.1 Central and Peripheral Tolerance
22.2 Graft Rejection
22.3 Immunosuppression
Additional Reading
23 Immunological Hypersensitivities: Allergy and Autoimmunity
23.1 Classification of Hypersensitivities
23.2 Immunity of Allergies
23.3 Type 2 and 3 Hypersensitivities
23.4 T Cell-Mediated Autoimmunity
23.5 The Equilibrium Model of Immunity
Additional Reading
24 Introduction to Cancer
24.1 The Global Burden of Cancer
24.2 Categorization and Diagnosis of Tumors
24.3 Crucial Transitions in Cancer
24.4 Causes of Cancer
24.5 Cancer Prevention
Additional Reading
25 Oncogenes, Signal Transduction and the Hallmarks of Cancer
25.1 Cellular Transformation
25.2 Activating Oncogenes in Signal Transduction Pathways
25.3 Oncogenic Translocations and Amplifications
25.4 The Hallmarks of Cancer Concept
Additional Reading
26 Tumor Suppressor Genes and Cell Fate Control
26.1 p53—A Master Example Tumor Suppressor
26.2 Tumor Suppressors and Oncogenes in Cell Cycle Control
26.3 Tumor Suppressor Inhibition and Cancer Onset
Additional Reading
27 Multistep Tumorigenesis and Genome Instability
27.1 Characteristics of Tumor Growth
27.2 Multistep Tumorigenesis
27.3 Genome Instability
27.4 Cancer Driver Mutations and Genes
Additional Reading
28 Cancer Genomics
28.1 Human Genetic Variation and Cancer Susceptibility
28.2 The Cancer Genome
28.3 Cancer Genome Projects
Additional Reading
29 Cancer Epigenomics
29.1 Epigenetic Mechanisms of Cancer
29.2 DNA Methylation and Cancer
29.3 Chromatin Changes and Cancer
Additional Reading
30 Aging and Cancer
30.1 Central Role of Aging During Chronic Diseases
30.2 The Hallmarks of Aging
30.3 Telomeres and Replicative Immortality
Additional Reading
31 Tumor Microenvironment
31.1 The Impact of the Wound Healing Program for Cancer
31.2 Cell Types of the Tumor Microenvironment
31.3 Inducing Angiogenesis
31.4 Tumor-Promoting Inflammation
31.5 Deregulating Cellular Energetics
Additional Reading
32 Metastasis and Cachexia
32.1 The Metastatic Cascade
32.2 Epithelial-Mesenchymal Transition
32.3 Metastatic Colonization
32.4 Cachexia
Additional Reading
33 Cancer Immunology
33.1 Outline of Cancer Immunity
33.2 Recognition of Cancer Antigens
33.3 Monoclonal Antibodies in Cancer Immunotherapy
33.4 Immune Cell Therapies
Additional Reading
34 Architecture of Cancer Therapies
34.1 Classical Cancer Treatments
34.2 Targeted Therapies
34.3 Precision Oncology
Additional Reading
35 Nutrition and Common Diseases
35.1 Evolution of Human Nutrition
35.2 Principles of Metabolism
35.3 Dietary Molecules and Their Sensing
35.4 Nutrition and Metabolic Diseases
35.5 Impact of Physical Activity
Additional Reading
36 Interference of the Human Genome with Nutrients
36.1 Human Genetic Adaptions
36.2 Genetic Adaption to Dietary Changes
36.3 Regulatory SNPs and Quantitative Traits
36.4 Definition of Nutrigenomics
36.5 Personal Omics Profiles
Additional Reading
37 Nutritional Epigenetics, Signaling and Aging
37.1 Intermediary Metabolism and Epigenetic Signaling
37.2 Aging and Conserved Nutrient-Sensing Pathways
37.3 Neuroendocrine Regulation of Aging
37.4 Principles of Insulin Signaling
37.5 Central Role of FOXO Transcription Factors
37.6 Calorie Restriction from Yeast to Mammals
37.7 Cellular Energy Status Sensing by SIRTs and AMPK
Additional Reading
38 Chronic Inflammation and Metabolic Stress
38.1 Acute and Chronic Inflammation
38.2 Reverse Cholesterol Transport and Inflammation
38.3 Sensing Metabolic Stress via the ER
Additional Reading
39 Obesity
39.1 Definition of Obesity
39.2 Adipogenesis
39.3 Inflammation in Adipose Tissue
39.4 Energy Homeostasis and Hormonal Regulation of Food Uptake
39.5 Genetics of Obesity
Additional Reading
40 Insulin Resistance and Diabetes
40.1 Glucose Homeostasis
40.2 Insulin Resistance in Skeletal Muscle and Liver
40.3 β Cell Failure
40.4 Definition of Diabetes
40.5 Failure of Glucose Homeostasis in T2D and Its Treatment
40.6 Genetics and Epigenetics of T2D
Additional Reading
41 Heart Disease and the Metabolic Syndrome
41.1 Hypertension
41.2 Mechanisms of Atherosclerosis
41.3 Lipoproteins and Dyslipidemias
41.4 Whole Body’s Perspective of the Metabolic Syndrome
41.5 Metabolic Syndrome in Key Metabolic Organs
41.6 Genetics and Epigenetics of the Metabolic Syndrome
Additional Reading
42 Epigenetics, Inflammation and Disease
42.1 Genetics, Epigenetics and Environment
42.2 Central Relation of Epigenetics and Immunity
Additional Reading
Glossary
