Home » Claude D. Pepper Older Americans Independence Center (OAIC) » Cores » Pilot/Exploratory Studies Core (PESC)

Pilot/Exploratory Studies Core (PESC)

The overall objective of the Pilot/Exploratory Studies Core (PESC) of the Duke OAIC is to conduct pilot studies that inform the selection, design, and conduct of subsequent larger, hypothesis-driven research in our theme:
To understand and optimize reserve and resilience

The Pilot/Exploratory Studies Core emphasizes physiological reserve at the cell/tissue/organ level, which we hypothesize is a key contributor to resilience at the whole person level.

AIMS of the Pilot/Exploratory Studies Core
  1. To advance top quality science related to late-life reserve and resilience
  2. To attract and nurture a diverse cadre of outstanding early investigators in aging research or established investigators pursuing promising new directions related to our theme
  3. To build and sustain relationships with critical stakeholders to maximize the impact and translation of the work conducted through this and future OAICs

CORE LEADERS
Heather E. Whitson, MD, MHS
Associate Professor of Medicine & Ophthalmology
Director, Center for the Study of Aging and Human Development

Dr. Whitson’s research is focused on improving care and health outcomes for people with multiple chronic conditions. In particular, she has interest and expertise related to the link between changes in the eye and brain (e.g., Why do cognitive and brain changes occur in the context of late-life vision loss? Is Alzheimer’s Disease associated with distinctive changes in the retina, and could such changes help diagnose Alzheimer’s early in its course?). She has developed a novel rehabilitation model for people with co-existing cognitive deficits, and is part of an inter-disciplinary team seeking to improve peri-operative outcomes for frail or at-risk seniors who must undergo surgery. In 2018, Dr Whitson received the Thomas and Catherine Yoshikawa Award for Outstanding Scientific Achievement in Clinical Investigation from the American Geriatrics Society.

William E. Kraus, MD
Richard and Pat Johnson University Professor of Medicine
Director of Clinical Translation, DMPI

One focus of my group’s work is to understand the cellular signaling mechanisms underlying the normal adaptive responses of skeletal muscle to physiologic stimuli, such as occur in exercise conditioning, and to understand the abnormal maladaptive responses that occur in response to pathophysiologic stimuli, such as occur in congestive heart failure, aging and prolonged exposure to microgravity. Recently we have begun to investigate interactions of genes and lifestyle interventions on cardiometabolic outcomes. We have experience with clinical lifestyle intervention studies, particularly the contributions of genetic variants to interventions responses. We call this Lifestyle Medicopharmacogenetics. In February 2018, Dr Kraus was elected President-Elect of the American College of Sports Medicine. He will serve as President for a year commencing June 2019.

2020 PILOT STUDY AWARDS
Gurpreet Baht, PhD (Department of Orthopaedic Surgery)
ApoE: A new target to improve aged bone healing

  1. Aim 1: Develop a therapeutic intervention to improve aged bone fracture healing. In our recent study, we showed that lowered circulating ApoE levels in knockout mice were associated with improved aged fracture repair. To test whether temporarily lowering circulating ApoE levels during fracture healing will improve fracture outcome, we will perform fracture studies with small molecule reverse agonists to a nuclear receptor that controls ApoE expression.
  2. Aim 2: Identify the immunophenotypic differences in the fracture calluses of aged mice treated with inhibitors of ApoE expression. We hypothesize that ApoE-based age-associated changes in fracture repair are due to changes in the immunophenotype of the fracture callus.

Elaine Gomez Guevara, PhD (Dept. of Evolutionary Anthropology)
Mechanisms underlying variation in primate physiological reserve

  1. Aim 1: Measure oxidative stress and telomere dynamics across the lifespan in species of Lemur (fast maturation, shorter lifespan than Propithecus, while sympatric) and Propithecus (extreme longevity for body size in nature, very slow development, low rate of actuarial senescence, evidence for enhanced somatic maintenance).
  2. Aim 2: Validate inflammatory biomarkers as age-related markers in these models.

Gentzon Hall, MD, PhD (Division of Nephrology/Dept. of Medicine)
Understanding the role of IL-15 signaling in podocyte resilience and survival

Hypothesis: A functioning IL-15/IL-15R axis is essential for homeostatic prosurvival signaling in podocytes and impaired IL-15 signaling reduces podocyte resiliency to proapototic stimuli, increasing risk of glomerulosclerosis.

  1. Aim 1: To characterize the effects of IL-15/IL-15R knockdown a) on podocyte resiliency and loss in response to proapoptotic stimuli and b) on signaling through three prosurvival transcriptional regulatory pathways.
  2. Aim 2: To characterize the effects of targeted IL-15/IL-15R KD on pronephric integrity and function in DBP-GFP zebrafish.

Adam DeVore, MD, MHS (Division of Cardiology/Dept. of Medicine)
Resilience after heart transplant or LVAD in patients with advanced heart failure

  1. Aim 1: To determine the feasibility of a comprehensive assessment to predict resilience and to describe normative values in patients with advanced heart failure. We will enroll approximately 50 patients undergoing evaluation for heart transplant or LVAD at Duke. We will collect information on the completion rate of each assessment during the study protocol and collect qualitative data from the study teams on feasibility and study burden.
  2. Aim 2: To describe at what time point after surgery patients with advanced heart failure recover using assessments of physical, cognitive and psychosocial health.

2018 PILOT STUDIES IN-PROGRESS
David Bartlett, PhD (Division of Medical Oncology/Dept. of Medicine)
Exercise training to promote resilience in chronic lymphocytic leukemia (CLL) in older patients by enhancing physical and immunological reserve

  1. His laboratory studies the effects of exercise and energy balance on immune function and physiology of patient groups including cancer, arthritis and diabetes. His research program is focused on human studies employing a wide range of techniques including human physiological testing such as cardiopulmonary fitness assessment, exercise training to in vitro and ex vivo cellular assays.
  2. Aim 1: To determine changes in physical reserve (aerobic capacity and strength) following 12-weeks of supervised exercise training in older adults with CLL.
  3. Aim 2: To determine the relationships between changes in aerobic capacity and immunological mediators of improved resilience against CLL.
  4. In both non-exercise (n=10) and exercise (n=10) groups we will assess immunological reserve by changes in 1) lymphocyte doubling rate 2) neutrophil: lymphocyte and lymphocyte: monocyte ratios 3) NK-cell tumor cytotoxicity and 4) bacterial phagocytosis.
  5. Current status: 16 have completed study, now on hold due to COVID. MMC will run analyses and dataset being prepared for Analysis Core. 2 abstracts accepted; Awarded American Society of Hematology Junior Faculty Award ($150K over 2 years).

Anna Mae Diehl, MD (Division of Gastroenterology/Dept. of Medicine)
Aging Effects on Hepatocyte Reprogramming and Liver Repair

  1. The Diehl lab’s studies on liver regeneration in young adult rodents reveal a signaling network that controls adult-to-fetal and fetal-to-adult reprogramming in hepatocytes. These findings extend work by others showing that the Hippo Kinase (HK) pathway and its downstream target, Yap1, critically regulate regenerative reprogramming in hepatocytes. Moreover, long-lived somatic cells of organs that are inherently less resilient than the liver can be coaxed to undergo the adult-to-fetal reprogramming process that occurs naturally in adult hepatocytes when they activate endogenous Yap1 during a regenerative stress. The Diehl lab seeks to advance knowledge that ultimately can be applied to promote more favorable response to stressors in a variety of aging tissues.

Charity Oyedeji, MD (Division of Hematology/Dept. of Medicine)
Focused geriatric assessment and biomarkers to determine physiologic resilience in older adults with sickle cell disease

  1. Older adults (defined herein as age ≥ 50 years) make up 13% of the adults with sickle cell disease cared for at The Duke Sickle Cell Center. This population has experienced a lifetime of sickling and microvascular occlusion that has an effect on every organ of the body. This often leads to a functional decline and premature aging.
  2. Aim 1: To evaluate the feasibility of focused geriatric assessment in twenty older adults (age ≥ 50 years) with sickle cell disease.
  3. Aim 2: To assess the feasibility of a protocol to measure resilience of older adults with sickle cell disease after hospitalization.
  4. Aim 3: To estimate the variability of biomarkers of inflammation, coagulation, and longevity in 20 older adults with sickle cell disease.
  5. Current status: 21 older adults (OA) have completed baseline assessment; also recruited 21 young controls (3 pending due to COVID). 11 OA and 1 control hospitalized so far. >80% completed post-hospital assessment with 20 days, others within 30 days. Oral presentation at the 2019 American Society of Hematology annual meeting.

Mihai Podgoreanu, MD (Cardiothoracic Anesthesia and Critical Care)
Metabolic modifiers and rehabilitation phenotypes in older adults subjected to extracorporeal support (METAMORPHOSES)

  1. Aim 1: Determine the feasibility of recruitment and data collection protocols needed to estimate functional trajectories among Duke ECMO patients receiving ICU rehabilitation.
  2. Aim 2: Determine the feasibility of sample collection and processing protocols needed to quantify metabolic markers that may correlate to recovery phenotypes.
  3. Current status: Longitudinal functional measures on 100+ patients to be analyzed over next year (Aim 1). Without additional staff, not feasible to collect prospective baseline biomarker data due to challenges with obtaining consent (Aim 2).
RECENTLY COMPLETED PROJECTS
Miles Berger, MD Pre-operative Exercise to Enhance Resilience to Surgery in Older Adults
Amy McNulty, PhD Rejuvenation of Aging Chondrocytes to Enhance Reserve and Prevent Osteoarthritis
James White, Jr PhD The Role of Autophagy in Function of Aged Satellite Cells: Optimizing Muscle Reserve

PREVIOUS PEPPER PILOT/EXPLORATORY STUDIES

James White, Jr PhD, Duke Molecular Physiology Institute (2016-2018)
The Role of Autophagy in Function of Aged Satellite Cells: Optimizing Muscle Reserve

Amy McNulty, PhD, Orthopedic Surgery (2015-2017)
Rejuvenation of Aging Chondrocytes to Enhance Reserve and Prevent Osteoarthritis

Miles Berger, MD, Anesthesiology (2015-2017)
Pre-operative Exercise to Enhance Resilience to Surgery in Older Adults

Dan Belsky, PhD, Geriatrics (2014-2016)
A Pilot Study to Identify Physiological Vulnerabilities to Accelerated Functional Decline
[Quantification of molecular signatures of resilience in aging]

Nancy Allen, MD, Rheumatology and Immunology
Metabolic effects of combined exercise on skeletal muscle in older adults

Farshid Guilak, PhD, Orthopedic Surgery and Cell Biology (2014-2016)
Epigenetic Modification of Stem Cells with Aging and Obesity

Susan Nichole Hastings, MD, Geriatrics (2014-2016)
Skeletal Muscle Mass and Strength Trajectories in Older Patients Hospitalized with Medical Illness

Matthew Hirschey, PhD, Chemistry and Biochemistry (2014-2016)
Determining the Role of Protein Quality Control in Mitochondrial Dysfunction and Disease in Aging

Kimberly Johnson, MD, Geriatrics (2014-2016)
Racial Differences in Outcomes of Older Adults Receiving Inpatient Palliative Care Consultation

Katherine Hall, PhD, Geriatrics (2013-ongoing)
Accelerometry Data for Physical Activity and Sedentary Behavior in Older Adults:
Data Processing and Analysis

Juliessa Pavon, MD, Geriatrics (2013-ongoing)
Improving Venous Thromboembolism Prophylaxis in Hospitalized Elders

John Stiber, MD, Cardiology (2013-2014)
Role of Protein Scaffolding in Sarcopenia

Cathleen Colon-Emeric, MD, Geriatrics (2011-2016)
Outcomes of Nursing Management Practices in Nursing Homes

Jason Allen, PhD (2011-2013)
Mechanisms and Functional Outcomes of Exercise Progression Models in the Elderly

Raquel R. Bartz, MD, Anesthesiology (2011-2013)
Role of Organ and Immune Cell Mitochondrial Biogenesis in Exercise-trained Old Mice
In Response to Staphylococcal Sepsis

Arati Rao, MD (2011-2013)
Linking Genomic Predictors of Frailty to Functional Status of Elderly Acute Myeloid Leukemia (AML) Patients

Amy Pastva, PT, PhD, Physical Therapy (2009-2010)
Aerobic Exercising Training and Attenuation of the Susceptibility of Older Adults to Endotoxin-Induced Lung Injury
(Small Exploratory Study)

Tim Koves, PhD, Geriatrics (2009-2010)
Aging, Inflammatory Markers and Obesity
(Small Exploratory Study)

Helen Lum, MD, Geriatrics (2009-2010)
The Role of Oxidative Stress in Metabolism and Physical Performance
(Small Exploratory Study)

Virginia Kraus, MD, PhD, Rheumatology & Immunology (2009-2010)
Characterizing Age-related Post Translational Protein Modifications by Mass Spectroscopy
(Administrative Supplement)

Elizabeth Hauser, PhD, Genetics (2009-2010)
Identifying Epigenetic Targets of Aging and Atherosclerosis
(Administrative Supplement)

Jason Allen, PhD (2009-2010)
Elevated Plasma Nitrite via Dietary Nitrate Supplementation and Its Effects
On Vascular Endothelial Function and Physical Function in the Elderly
(Small Exploratory Study)

Lee Jones, PhD (2009-2010)
Effect of Aerobic Training on Cardiopulmonary Function and Quality of Life
In Postsurgical Lung Cancer Patients
(Small Exploratory Study)

Jessica Chia, MD (2009-2010)
Role of Aging and Endoplasmic Reticulum Stress in the Pathogenesis of Pulmonary Fibrosis
(Small Exploratory Study)

David Madden, PhD, Psychiatry and Behavioral Sciences (2009-2010)
Neuronal Dysregulation and Disintegration in Function in Frail Older Adults
(Small Exploratory Study)

Greg Sempowski, PhD (2009-2010)
Impact of Zoledronic Acid on Immune Function in Aged and Young Mice
(Small Exploratory Study)

Tim Koves, PhD, Geriatrics (2009-2010)
The Relationship of Gait to Age, Muscle Strength and Endurance in a Mouse Model
With Partially Blunted of Fatty Acid Oxidation
(Small Exploratory Study)

Kelli Dominick Allen, PhD, General Internal Medicine (2008-10)
Strength and Gait Training for Older Adults with Knee Osteoarthritis and Varus Malalignment

Beverly H. Brummett, PhD, Psychiatry (2008-10)
Positive Emotion and Functioning in Older Adults

William M. Foster, PhD, (2008-10)
Genetic Factors and Differential Response of the Elderly to Ozone:
Effects on Lung Function, and Epithelial Integrity

Svati H. Shah, MD, MHS, Epidemiology, Medical Genomics (2006-2007, 2007-2008)
Gene-Environment Interactions in Aging, Functional Decline and Disease

James T. Cavenaugh, PT, PhD (2006-2007, 2007-2008)
Executive Function and Ambulatory Activity in Older Adults

Deborah Muoio, PhD (2006-2007, 2007-2008)
Lipid Induced Mitochondrial Dysfunction and Age-Related Insulin Resistance

Kimberly Johnson, MD (2004-2005)
Cultural Differences in End-of-Life Care: The African-American Experience

Keith S. Kaye, MD, MPH, Infectious Diseases (2003-2004)
Hospital-Acquired Infections in the Elderly

David Seo, MD (2002-2003)
Gene Expression Profiling of Murine Models of Atherosclerosis

Susan Hedayati, MD (2002-2003)
Depression and Outcomes in Patients with End-Stage Renal Disease on Hemodialysis

Dennis Turner, MD, Surgery and Neurobiology (2002-2003)
Outcome Analysis of Cervical Spondylotic Myelopathy

Maragatha Kuchibhatla, PhD, Geriatrics (2002-2003)
Use of Classification Trees in the Diagnosis of Mild Cognitive Impairment and Dementia

Beverly Fermor, PhD (2001-2002)
The Role of Age on Mechanical Stress Induced Changes in Matrix Turnover in Articular Cartilage

David F. Lobach, MD, PhD, MS, Clinical Informatics (2001-2002)
Web-Based Patient Recruiting for Clinical Trials

Virginia Kraus, MD (2001-2002)
Roles of Age on Mechanical Stress

Gregory Taylor, PhD (2000-2001)
Effectiveness of PspA Pneumococcal Vaccines in Aged Mice

Silke A. Schmidt, PhD (2000-2001)
Age-Related Macular Degeneration

Mitchell Heflin, MD, Geriatrics (2000-2001)
Survey of Providers on Cancer Screening in the Elderly

Sandhya A. Lagoo-Deenadayalan, MD (2000-2001)
Aging and Immune Response to Surgical Stress and Sepsis

Dhaval Kumar Patel, MD (2000-2001)
Developing Expression Proteomics Assays to Study Aging

David Edelman, MD (1999-2000)
Screening Elderly Primary Care Patients for Diabetes

Rodney J. Folz, MD, PhD (1999-2000)
Cellular Aging and Extra Cellular Antioxidants

William Scott, PhD (1999-2000)
Genetics of Successful Aging in the Midwestern Amish

Jeremy Sugarman, MD, MPH, Medical Ethics (1995-1996)
Getting Meaningful Informed Consent for Research in the Elderly:
A Structured Literature Review of Empirical Research

Michael J. Econs, MD (1995-1996)
Genetic Studies in Paget’s Disease of Bone

Connie Bales, PhD, Geriatrics (1995-1996)
The Relationship of Age with Indicators of Oxidative Status:
A Potential Opportunity for Studying Aging Process and Life-Style Factors Which Affect It

Martin Sullivan, MD (1995-1996)
The Effects of Long Term Psychologic Intervention on Functional Status of Patients with Heart Failure

Debra A. Schwinn, MD (1995-1996)
Effect of Aging on Acute Myocardial B-Adrenergic Receptor Desensitization During Cardiopulmonary Bypass

Amrit Singh, MD, Geriatrics (1994-1995)
Evaluation of Pain Behavior Detection by Long Term Care Facility Nursing Personnel

Barbara Tardiff, MD, Cardiac Anesthesia (1994-95)
Apolipoprotein E. Allele Frequency in Patients with Cognitive Deficits Following Cardiopulmonary Bypass

Debra Weiner, MD, Geriatrics
Lumbosacral Osteoarthritis in the Elderly: Examining Pain as a Mediator of Progression from Pathology to Disability

Douglas McCrory, MD
Patient Preferences for Treatment and Outcomes of Rheumatoid Arthritis

Heidi White, MD, Geriatrics (1994-1995)
Weight Change in Alzheimer’s Disease: An Analysis of Morbidity, Mortality and Associated Factors

Miriam Smyth, MD (1994-1996)
Interference with the Role of Sphingomyelinase in Cell Senescence: An Anti-Aging Strategy

Wei Jiang, MD (1994-1995)
A Pilot Study for a Clinical Trial to Evaluate the Effects of Paroxetine on Transient Myocardial Ischemia
and Cardiac Events in Older Patients with Coronary Disease Accompanied by Depression

Virginia B. Kraus, MD (1994-1995)
Genetic Studies of Familial Forms of Osteoarthritis

Michael Econs, MD (1994-95)
The Genetic Aspects of Osteoporosis in Elderly African-Americans and Caucasians

Julie Chandler, PhD, PT, Physical Therapy (1993-1994)
The Personal Functional Goals Interview Protocol: A Refinement and Validation Study
in Patients with Ischemic Stroke

Lynn Hobin, DMD, Geriatric Dentistry (1993-1994)
Increased Resistance to Artificially Induced Carious Lesions in Root Surfaces

Toni Cutson, MD (1993-1994)
Development of a New Clinical Scale for Parkinson’s Disease

Tony Galanos, MD (1993-1994)
Relationship between Body Mass Index and Functional Status

Mark Stanton, MD (1993-1994)
A Randomized Controlled Trial of Pulmonary Rehabilitation

Maya McNeilly, PhD (1993-1994)
Community Based African/Aerobic Exercise Intervention to Improve Cardiovascular Fitness, Exercise Adherence,
and Psychological Well-being, and Reduce Blood Pressure and Weight in Older, African-Americans

Larry Goldstein, MD (1992-1993)
Double-Blind, Randomized Pilot Study Evaluating the Effect of D-Amphetamine on Motor Recovery

Miriam C. Morey, MA, Gerontology (1991-1992)
A Comparison of the Effects of Fitness and Acute Exercise on the Sleep of Older Women

RECENT PUBLICATIONS

Nobuhara CK, Bullock WM, Bunning T, Colin B, Cooter M, Devinney MJ, Ferrandino MN, Gadsden J, Garrigues G, Habib AS, Moretti E, Moul J, Ohlendorf B, Sandler A, Scheri R, Sharma B, Thomas JP, Young C, Mathew JP, Berger M; MADCO-PC and INTUIT Investigators Teams. A protocol to reduce self-reported pain scores and adverse events following lumbar punctures in older adults. J Neurol. 2020 Mar 20. [Institutional access] [PubMed]

Baht GS, Bareja A, Lee DE, Rao RR, Huang R, Huebner J, Bartlett D, Hart C, Gibson J, Lanza I, Kraus V, Gregory S, Spiegelman B, White J. Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism. Nature Metabolism. 2020 Feb;68(2):261-265. [Institutional access]

Oyedeji C, Strouse JJ, Crawford RD, Garett ME, Ashley-Koch AE, Telen MJ. A Multi-institutional Comparison of Younger and Older Adults with Sickle Cell Disease. Am J Hematol. 2019 Apr;94(4):E115-E117. [Institutional access] [PMC free article] [PubMed]

Lee DE, Bareja A, Bartlett DB, White JP. Autophagy as a Therapeutic Target to Enhance Aged Muscle Regeneration. Cells. 2019 Feb 20;8(2). pii: E183. [Open Access] [PMC free article] [PubMed]

Kraus WE, Pieper CF, Huffman KM, Thompson DK, Kraus VB, Morey MC, Cohen HJ, Ravussin E, Redman LM, Bain JR, Stevens RD, Newgard CB. Association of Plasma Small-Molecule Intermediate Metabolites With Age and Body Mass Index Across Six Diverse Study Populations. J Gerontol A Biol Sci Med Sci 2016 Nov;71(11):1507-1513. [Institutional access] [PMC free article] [PubMed]

Whitson HE, Duan-Porter W, Schmader KE, Morey MC, Cohen HJ, Colón-Emeric CS. Physical Resilience in Older Adults: Systematic Review and Development of an Emerging Construct. J Gerontol A Biol Sci Med Sci 2016 Apr;71(4):489-495. [PMC free article] [PubMed]