Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. 

In the President’s 2016 Budget, President Obama unveiled the Precision Medicine Initiative —  a bold new enterprise to revolutionize medicine and generate the scientific evidence needed to move the concept of precision medicine into every day clinical practice. More information about the President’s Precision Medicine Initiative can be found at:

The National Institute of Nursing Research (NINR) supports research to develop personalized strategies to prevent and manage the adverse symptoms of illness across diverse populations and settings. At the Bethesda MD campus and across the Nation, NINR-supported scientists are actively engaged in implementing clinical applications of genomics and other ‘omics science’. These symptom scientists seek to improve health and symptom outcomes, guided by the vision reflected in the Precision Medicine Initiative, to accelerate discoveries that can provide clinicians with new tools, knowledge, and therapies to select which interventions will work best for which patients.

Precision Medicine at NINR

Through an emphasis on symptom science, NINR-supported scientists are contributing findings that can predict which people are most at-risk for adverse symptoms and conditions, monitor treatment efficacy, and guide interventions to improve health and symptom outcomes. NINR has established a model to guide research related to symptoms of illnesses, injuries, and conditions.

This model, known as the National Institutes of Health Symptom Science Model (NIH/SSM)[i] guides scientists through a process of:

  • Identifying complex symptoms or clusters;

  • Clarifying and standardizing how these symptoms can be measured and identified across multiple groups and/or conditions;

  • Identifying biological elements (“biomarkers”) associated with symptoms and symptom experiences across populations and conditions; and

  • Developing treatments and interventions that prevent or reduce these symptoms

NINR Intramural Research – Implementing Symptom Science and Precision Medicine

The scientists in NINR’s intramural research program implement the NIH/SSM with the goal of enhancing patient outcomes. To develop the scientific foundation for individualized prevention and management strategies, NINR intramural scientists undertake leading-edge symptom science research to determine the underlying biologic and behavioral mechanisms of symptoms associated with a variety of disorders.

For many years, NINR’s intramural science has been guided by the same scientific vision underlying the Precision Medicine Initiative. For example, NINR intramural scientists are currently:

  • Examining how radiation-induced changes at the genetic level are related to treatment-related fatigue in prostate cancer patients[ii]

  • Exploring mechanisms to reduce oxidative stress, fatigability, and fatigue in patients with the RYR1-related congenital myopathy muscle disorder[iii]

  • Illuminating the mechanisms involved in symptom distress related to digestive disorders, specifically the biobehavioral relationships between inflammation and patient symptoms.[iv]

  • Evaluating the contribution of genetic and epigenetic factors to the various types of acute and chronic symptoms and their interactions with bio-behavioral factors and therapeutic interventions[v]
     

NINR intramural scientists have also produced research findings in symptom science. Examples include:

  • Finding that a protein previously linked to acute symptoms following a traumatic brain injury (TBI) may also be responsible for long-term complications from TBI[vi]

  • Identification of two miRNAs that link to pain and inflammatory pathways likely dysregulated in IBS which may lead to the differentiation of GI symptoms and to additional miRNA targets for treatment[vii]

  • Discovering that military personnel with chronic symptoms following blast traumatic brain injury have differential expression of neuronal recovery and epidermal growth factor receptor genes[viii]

  • Discovering associations between inflammatory gene expression and fatigue intensification; and, illuminating proteomic serum profile changes in external beam radiation therapy (EBRT) patients with fatigue symptoms[ix]

  • Identification of a set of molecular pathways that may provide insights into the mechanisms of weight gain in kidney transplant recipients[x]

In addition, NINR maintains a commitment to providing scientific leadership and intensive research training to enhance the biologic and physiologic research foundation of the nurse scientist workforce. The NIH Symptom Science Model plays an integral part in training programs such as:

  • The Symptom Research Methodologies Boot Camp, a one-week research training course that provides a foundation in the latest research methodologies including big data, sleep/fatigue, and pain.

  • NINR-DIR’s Summer Genetics Institute provides training in molecular genetics to build the research capacity of the nursing science community and to expand clinical practice in genetics among clinicians.

NINR Extramural Research – Supporting Symptom Science and Precision Medicine

NINR-supported scientists in the extramural research community across the United States also contribute to advancing knowledge in symptom science in order to develop personalized prevention and management approaches for addressing symptoms such as pain and disordered sleep. Consistent with the Precision Medicine Initiative, these scientists are exploring how differences in individuals’ genes, environments, and behaviors affect how they experience the adverse symptoms of illness, and how these symptoms can best be managed.

Examples of symptom science research supported by NINR include:

  • Examining the biological and psychological mechanisms underlying abdominal pain and other symptoms by exploring the interplay of the microbiome, gastrointestinal permeability, immune responses, and psychological distress in women with irritable bowel syndrome[xi]

  • Developing knowledge about the role of sleep disruptions as modifiable risk factors of gestational diabetes mellitus to provide a new target for intervention on prevention and management of diabetes in pregnancy and establish a scientific basis to develop practice parameters for sleep problems in pregnancy[xii]

  • Identifying neuroimaging biomarkers to predict which individuals are most vulnerable to cognitive decline after knee replacement surgery, which may help researchers develop targeted interventions for vulnerable patients[xiii]
     

New advances in genomics and other fields have allowed nurse scientists to better understand the symptoms of chronic illness and to focus on developing personalized strategies to treat and prevent the adverse symptoms of illness. Select science advances include:

  • Three clusters of symptoms were identified in children with cancer undergoing chemotherapy, and understanding of these clusters could lead to more effective treatments[xiv]

  • Biomarkers of inflammation can help distinguish differences in the timing and severity of pain in breast cancer patients before and after surgery and chemotherapy[xv]

  • A team of scientists identified a new role for a protein that is associated with post-spinal cord injury pain, suggesting a new cellular target for developing and testing treatments for neuropathy[xvi]

Selected Funding Opportunities in Symptom Science include:

References



[i] Cashion AK, Grady PA. The National Institutes of Health/National Institute of Nursing Research intramural research program and the development of the National Institutes of Health Symptom Science Model. Nurs Outlook. 2015 Jul-Aug; 63(4): 484-7. PMID: 26187087

[ii] Saligan: ZIANR000019(20) - Investigating Correlates and Therapeutics of Fatigue (in Cancer Patients)

[iii] Meilleur: ZIANR000026 - Research in Congenital Muscle Disease

[iv] Henderson: ZIANR000018 - Symptom Distress Mechanisms in Digestive Disorders

[v] Cashion: ZIANR000015 - Genomic Analyses for Elucidating Novel Targets for Symptoms Management

[vi] Olivera A, Lejbman N, Jeromin A, French LM, Kim H, Cashion A, Mysleweic V, Diaz-Arrastia R, Gill J. 2015. Peripheral total tau in military personnel who sustain traumatic brain injuries  during deployment. JAMA Neurol. Aug 3. doi: 10.1001/jamaneurol.2015.1383

[vii] Fourie NH, Peace RM, Abey SK, Sherwin LB, Rahim-Williams B, Smyser PA, Wiley JW, Henderson WA. Elevated circulating miR-150 and miR-342-3p in patients with irritable bowel syndrome. Exp Mol Pathol. 2014 Jun;96(3):422-5. PubMed PMID: 24768587

[viii] Heinzelmann M, Reddy SY, French LM, Wang D, Lee H, Barr T, Baxter T, Mysliwiec V, Gill J. Military personnel with chronic symptoms following blast traumatic brain injury have differential expression of neuronal recovery and epidermal growth factor receptor genes. Front Neurol. 2014 Oct 9;5:198. PubMed PMID: 25346719

[ix] Hsiao CP, Wang D, Kaushal A, Chen MK, Saligan L. Differential expression of genes related to mitochondrial biogenesis and bioenergetics in fatigued prostate cancer men receiving external beam radiation therapy. J Pain Symptom Manage. 2014; 48:1080-90. PMID: 24786901

[x] Cashion A, Stanfill A, Thomas F, Xu L, Sutter T, Eason J, Ensell M, Homayouni R. Expression levels of obesity-related genes are associated with weight change in kidney transplant recipients. PLoS One. 2013;8(3):e59962, Epub 2013 Mar 27. PMID: 23544116

[xi] R01NR014479: Microbiome and Pain in IBS; Heitkemper (Contact) & Shulman, University of WA

[xii] R00NR013187: Sleep-Related Determinants of Gestational Diabetes; Izci-Balserak, Univ of IL at Chicago

[xiii] R01NR014181: Neuroimaging Biomarkers for Post-Operative Cognitive Decline in Older Adult; Price, Univ of FL

[xiv] Baggott C, Cooper BA, Marina N, Matthay KK, Miaskowski C. Symptom cluster analyses based on symptom occurrence and severity ratings among pediatric oncology patients during myelosuppressive chemotherapy. Cancer Nurs. 2012 Jan-Feb;35(1):19-28. PMID: 21921793

[xv] Starkweather AR, Lyon DE, Schubert CM. Pain and inflammation in women with early-stage breast cancer prior to induction of chemotherapy. Biol Res Nurs. 2013 Apr;15(2):234-41. PMID: 22084403

[xvi] Wu J, Renn CL, Faden AI, Dorsey SG.TrkB.T1 Contributes to Neuropathic Pain after Spinal Cord Injury through Regulation of Cell Cycle Pathways.J Neurosci. 2013 Jul 24;33(30):12447-63. PMID: 2388949