The recent emphasis in biomedical research on translational biology and personalized medicine is revolutionizing conceptual and experimental approaches to understanding and improving human health. Translational Biology in Medicine begins with an introduction to experimental model systems for disease, such as cell lines, primary cells, stem cells and animal models for disease, followed by a systematic description of genetic and genomic profiling and biomarker validation currently used in biomedical research. Examples of translation studies that have used these models and methods are presented, including studies in aging, tissue repair and chronic infection, each with an emphasis on how personalized medicine is transforming biomedicine. Bioethical considerations in translational study design and bioethical considerations in biomedical research are then covered, before concluding remarks, and a look towards the future of personalized medicine.•Describes cellular and animal model systems used in translational research •Discusses the use of blood, genetic and genomic biomarkers for disease •Presents translational studies in aging, tissue repair and infectious disease biomedicine

List of figures xiii

Abbreviations xv

About the author xxi

1 Introduction and overview of chapter contents 1

2 Model systems 9

2.1 Introduction 9

2.2 Immortalized cell lines 14

2.3 Primary cells obtained from the host 21

2.4 Animal models 27

2.5 Stem cells: adult and induced pluripotent 31

3 Blood biomarkers: overview of existing serum test strategies for disease severity, risk for progression, therapeutic benchmark targets 35

3.1 Introduction 36

3.2 Early definition of biomarkers 40

3.3 Initial biomarker discovery 41

3.4 Translation into animal models 42

3.5 Translation into small human populations 43

3.6 Application to larger, more generalizable populations 44

3.7 Biomarker measurement considerations 49

4 Genetic and genomic profiling 63

4.1 Introduction 63

4.2 Theories of heritability of disease risk and severity 64

4.3 Gene expression signatures 66

4.4 Examples of gene expression signatures 67

5 Translational models, methods and concepts in studies of aging and longevity 75

5.1 Introduction 76

5.2 Theories of aging 76

5.3 The here and now: the world is aging 78

5.4 Telomere length/activity in aging 80

5.5 Stem cell aging 82

5.6 Aging and muscle tissue regeneration 85

5.7 Immune aging and immunosenescence 85

5.8 The insulin/IGF1 signaling axis in aging 87

5.9 Branched-chain amino acids (BCAA) and aging 90

5.10 Measurement of lifespan modulators 91

5.11 Factors influencing aging 92

6 Translational models, methods and concepts In studies of muscle tissue 103

6.1 Introduction 104

6.2 Muscle maintenance and regeneration 105

6.3 The role of satellite cell activity in aging and decline in muscle function 107

6.4 Muscle growth regulatory pathways 111

6.5 Sarcopenia and muscle maintenance 117

6.6 Functional limitations and therapeutic drug design 120

6.7 The TGFbl axis 122

6.8 Inflammatory stress and muscle 122

6.9 Cachexia and muscle homeostasis 123

6.10 Anabolic effects of testosterone treatment 125

6.11 Use of high-throughput technologies with muscle to promote musculoskeletal growth 127

7 Translational models, methods and concepts in studies of acute and chronic infection 129

7.1 Introduction 130

7.2 From HIV origins to the modern era 132

7.3 HIV infection and aging 133

7.4 HIV-1 infection and transmission 135

7.5 Infection and innate host response 138

7.6 HIV and adaptive host response 140

7.7 HIV-1 comorbid conditions 143

7.8 HIV and drugs 147

7.9 Infection-associated inflammation and aging promote fibrosis 147

7.10 Viral eradication studies 148

8 Bioethical considerations and institutional review board (IRB) challenges in translatlonal study design and bioethical considerations In biomedlcal research 151

8.1 Institutional review boards 152

8.2 Institutional animal care and use committee (IACUC) 154

8.3 Big Data and the online privacy of health information 155

9 Concluding remarks and the future of personalized medicine 159

9.1 Introduction 159

9.2 Personalized medicine and aging 161

9.3 Personalized medicine and muscle maintenance 163

9.4 Personalized medicine and infectious diseases: HIV 165

References 167

Index 205

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