2016 Faculty Research Fellowship Awardees

Matthew Baldwin, MD, MS 

Assistant Professor of Medicine, Department of Pulmonary and Critical Care Medicine, Columbia University Medical Center

LATENT PHENOTYPES OF WEAKNESS AND TRAJECTORIES OF RECOVERY IN OLDER SURVIVORS OF CRITICAL ILLNESS

Older adults (over 65 years) comprise half of all intensive care unit (ICU) admissions and survive what were previously fatal critical illnesses, but disability and mortality in the first six months after hospital discharge remain high. Heterogeneity in trajectories of functional recovery among older ICU survivors suggests that there may be latent phenotypes of post-ICU weakness that may be identifiable at the time of hospital discharge. Identification of these latent weakness phenotypes will lead to personalized post-ICU rehabilitative interventions, and will facilitate the identification of mechanistic pathways that can be targeted in future clinical trials aiming to improve function and survival after critical illness. This project will leverage the clinical data and blood samples being collected in Dr. Baldwin’s ongoing, National Institute on Aging funded, prospective cohort study of older ICU survivors to accomplish the following aims: (1) identify and characterize novel latent phenotypes of weakness in older ICU survivors using a latent class analysis with clinical and biological measurements of frailty; and (2), test associations between these latent phenotypes and trajectories of functional recovery over 6 months. This project will be the first of its kind in the field of critical care outcomes research to use these personalized medicine approaches to improve post-ICU care.

Christine Denny, PhD

Assistant Professor of Clinical Neurobiology in Psychiatry, Division of Integrative Neuroscience, Department of Psychiatry, Columbia University Medical Center 

IDENTIFICATION AND OPTOGENETIC MANIPULATION OF INDIVIDUAL MEMORIES FOLLOWING AGE-RELATED COGNITIVE DECLINE

Age-related cognitive decline (ARCD) has deleterious effects on memory and poses a mounting public health burden. This chronic condition has become increasingly more common and necessitates a new perspective in order to understand how neural ensembles are become altered during dementia. Identifying the molecular alterations underlying ARCD will allow researchers to better understand and then develop target-specific treatments for age-related memory impairments. Recently, the Denny laboratory has developed a murine line that allows for the indelible labeling of individual memory traces or engrams. Using this line, they found that aged mice had impaired memories traces in the dentate gyrus (DG) and in CA3 subregions of the hippocampus. Optogenetic stimulation of these DG neural ensembles representing a contextual memory facilitated memory retrieval in aged mice, resulting in improved behavioral performance comparable to young mice. Together, these data point to DG manipulation as a potential target to correct age-related memory deficits. Here, the goal of this project is to identify the mechanisms underlying the success of optogenetic stimulation of DG neural ensembles by utilizing whole-brain 2-photon microscopy in order to identify the circuits that are compromised in memory loss and how they change when memory retrieval is improved.

Julie Herbstman, PhD

Associate Professor, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University

ENVIRONMETAL INFLUENCES OF LONGITUDINAL CHANGES IN BIOMAKERS OF HEALTH AGING

The concept of ‘healthy aging’ is based on maximizing and maintaining functional ability that enables optimal mental, social, and physical well-being and function in older adults. However, there are few ways to measure and monitor healthy aging. Inter-individual variability in the aging process, related to genetic as well as modifiable psychological, psychosocial, or environmental factors, indicates the need to acknowledge that chronological age represents a relatively imprecise measure of functional capacity and health. The long-term goal of this proposal is to build capacity to identify and validate biomarkers that can be used to monitor the impact of environmental exposures or potential interventions to promote healthy aging. This pilot study will build the foundation for future research in this area by characterizing the longitudinal change in four potential biomarkers of healthy aging over time including telomere length, DNA methylation to estimate biological age and peripheral blood cell distribution, and circulating brain-derived neurotrophic factor (BDNF) among middle-aged women. This study will also evaluate whether two environmental indicators—one chemical (air pollution) and one psychological (psychosocial stress)—measured repeatedly over time influence the longitudinal trajectory of these biomarkers.

Gerard Karsenty, MD, PhD

Paul A. Marks Professor of Genetics & Development, Professor of Medicine and Chair, Department of Genetics and Development, Columbia University

BONE REGULATION OF MUSCLE FUNCTION AND ITS IMPLICATION OF AGING

Muscle function and therefore exercise capacity decrease with age. In an effort to understand how these deleterious consequences of aging develop, the Karsenty lab has focused on another organ, whose functions are greatly affected by age: bone. Recently they have shown that the bone-derived hormone osteocalcin signals into myofibers to increase the uptake and catabolism of nutrients. As a result osteocalcin is necessary for muscle function during exercise and to maintain a healthy exercise capacity. The fact that circulating osteocalcin levels decrease with age led to a hypothesis that they propose to test: that osteocalcin signaling in myofibers may also be also sufficient to rescue the decrease in muscle functions that develop with aging. At the same time and based on the knowledge accumulated through this work, the Karsenty lab seeks to test whether a feed-forward loop between bone (via osteocalcin) and muscle (via interleukin 6) contributes to explain muscle function during exercise. Thus the overall goal of this project is to determine the extent to which osteocalcin signaling in muscle could be used as a treatment for age-related decline in muscle function.

Daphna Shohamy, PhD

Associate Professor, Department of Psychology, Zuckerman Institute, Columbia University

UNDERSTANDING THE EFFECTS OF AGING ON CURIOSITY AND LEARNING: NERUAL AND COGNITIVE MECHANISMS

Curiosity is a core aspect of cognition and an important driver of learning. It is associated with positive mental and physical health outcomes, greater quality of life, and even longevity. Yet, it has received surprisingly little research attention. Recent studies have begun to examine curiosity and its effects on learning in younger adults. But to date, the effects of healthy aging on curiosity remain unknown. Understanding how it is affected by healthy aging – at both a behavioral and neural level – could have important implications in our understanding of how curiosity might promote greater quality of life and how curiosity-motivated learning might serve to protect against cognitive decline. Pilot data from the Shohamy lab suggest that older adults report more curiosity and make more choices to learn new information, compared to younger adults. Therefore, the aim of this project is to (a) characterize how curiosity changes with aging, (b) understand how changes in curiosity affect the ability to learn and remember new information, and (c) reveal the neural circuits underlying these effects. This will be achieved by way of a large-sample study, combining fMRI with behavioral and computational assessments, to compare older and younger adults.

Richard Sloan, PhD

Nathaniel Wharton Professor of Behavioral Medicine,  Division Chief of Behavioral Medicine, Department of Psychiatry, Columbia University Medical Center

PLASTICITY IN RECOVERY FROM SURGERY: THE EFFECTS OF EXERCISE "REHABILITATION" ON COGNITIVE AND FUNCTIONAL RECOVERY AFTER SURGERY IN OLDER ADULTS  

Delayed recovery from surgery imposes enormous familial and societal costs. Because older patients are four times more likely to require a surgical intervention, the consequences fall disproportionately on older adults. Metrics by which recovery from surgical trauma can be measured include functional impairment, such as cognitive dysfunction, pain and fatigue. Recent evidence implicates the immune system in delayed recovery. Aerobic exercise training has been shown not only to enhance cognitive function in both animal and human models but also to attenuate systemic inflammation; so exercise appears to be relevant to a wide range of poor outcomes following surgery and speaks to the plasticity of these functions. Indeed, recent developments in neuroscience and immunology show how modifiable, especially by exercise training, these systems are. The anti-inflammatory and cognition enhancing effects of exercise training are an expression of a paradigm shift in views about neuroplasticity. The Sloan lab proposes to collect pilot data from patients awaiting shoulder replacement surgery who are randomized to a 4-week high-intensity interval training program or a control condition. Measures of inflammation and immune indices and cognitive function will be collected prior to surgery and at one, two, and three days after surgery. This proposed project will bring together investigators from Columbia, UCSF, and Stanford.