T32 Program Faculty Research Overview

 
Program Faculty

Research Interests

Charles A. Czeisler, PhD, MD: Human circadian pacemaker and sleep homeostat; photic circadian resetting; sleep and public policy; occupational health and safety. Dr. Czeisler and colleagues discovered that retinal light exposure, including exposure to ordinary indoor room light, resets the human circadian pacemaker. They have demonstrated that the resetting response depends on the timing, intensity, duration, continuity and wavelength of the light exposure, and that these findings could be applied to treat shift work sleep disorder. They have also demonstrated that the intrinsic period of the human circadian pacemaker is more stable, precise and closer to 24-hours than previously recognized, remaining stable with age, and is shorter in women than in men. Dr. Czeisler’s research has contributed to the diagnosis and treatment of delayed and advanced sleep phase disorders, non-24-hour sleep-wake disorder, shift work disorder and jet lag disorder. Moreover, the Harvard Work Hours, Health and Safety Group has demonstrated that extended duration (>24 hour) work shifts of hospital interns increase the risk of attentional failures, serious medical errors, adverse events (including fatal adverse events), occupational (needle stick) injuries, and motor vehicle crashes and that sleep disorders are prevalent in police and firefighters and associated with adverse health and safety outcomes. Dr. Czeisler is the Frank Baldino Professor of Sleep Medicine at Harvard Medical School, is a member of the Institute of Medicine of the National Academies and is internationally recognized for his scientific discoveries.

Radhika Basheer, PhD: Molecular and cellular mechanisms involved in the regulation of sleep-wake- behavior and sleep homeostasis. Recent work links brain energy metabolism and sleep-wakefulness. Her research strategies combine behavioral studies with molecular, biochemical and state- of-the-art optogenetics to understand the mechanisms regulating sleep-wake behavior. Dr. Basheer trained in Dr. McCarley’s lab.

Emery N. Brown, MD, PhD: Signal processing algorithms for neuroscience data analysis; functional neural imaging studies of humans under general anesthesia and sleep. Dr. Brown and colleagues have developed statistical methods to estimate circadian, ultradian and pharmacokinetic properties of melatonin and cortisol. Dr. Brown is a product of our training program and is an excellent example of our success in developing high caliber minority leaders. Dr. Brown is the Warren Zapol Professor of Anesthesiology at Massachusetts General Hospital and Massachusetts Institute of Technology, Edward Hood Taplin Professor of Medical Engineering and of Computational Neuroscience, Massachusetts Institute of Technology, and Professor of Health Sciences and Technology, Massachusetts Institute of Technology and Harvard Medical School. Dr. Brown is also the Director of the Harvard-MIT Health Sciences and Technology Program, MIT, Associate Director of the Institute for Medical Engineering and Science, MIT, and an investigator at the Picower Center for Learning and Memory, Department of Brain and Cognitive Sciences, MIT.  Dr. Brown is a member of the National Academy of Medicine.  Dr. Brown began his career as a postdoctoral fellow in Dr. Czeisler’s laboratory.

Ritchie Brown, PhD’s lab aims to reveal the brain circuits and cellular mechanisms which ‘wake up’ the cerebral cortex and lead to conscious awareness. We apply this knowledge to animal models of neuropsychiatric disease. Furthermore, we disseminate this knowledge through the writing of comprehensive review articles and book chapters, training junior researchers and teaching medical residents. In our research, we use genetically modified mice which allow us to target particular subgroups of subcortical neurons to study their location, electrical properties, pharmacology and their interaction with other neurons involved in cortical activation using immunohistochemistry, tract tracing, in vitro patch-clamp recordings and optogenetics. Together with other faculty members in our department we investigate the role of these subcortical neurons in the control of behavior and cortical activity using optogenetic and chemogenetic techniques in combination with EEG/EMG recordings and behavioral analysis.

Alec J. Davidson, PhD’s laboratory investigates how mammalian circadian organization arises, how it responds to environmental stimuli, how it becomes disrupted in altered lighting environments, and what the physiological consequences are of this disruption.

Jason DeBruyne, PhD’s is focused on identifying genes and mechanisms that drive daily circadian rhythms and regulate sleep, focusing a class of genes called ubiquitin ligases. Ubiquitin ligases generally function to induce the degradation of gene-products and are expected to play an essential role in how the clock driving circadian rhythms operates.

Michael H. Do, PhD: Pathways in the mammalian visual system, from their origin in the retina to their influences downstream. His work has provided important insight into how a common signal, light, is diversified by neural circuits to serve a variety of behavioral needs.

Francis J. Doyle, III, PhD: Research in the Doyle group examines biological systems using a control theory and complex systems framework, along with mathematical modeling. Our research on the circadian system is primarily focused on developing a mathematical understanding of the genetic components of the mammalian clock, and how communication between and within the suprachiasmatic nucleus master clock and peripheral tissues is established. We are especially interested in how circadian rhythms are precise, robust, and tunable at the organism-level despite being generated by “sloppy” cell autonomous circuits. Recent work within the group has shown that clock precision is an independently-tunable feature of the clock. Studying the naturally-robust architecture of the circadian clock allows us to identify design principles for creation of robust synthetic circuits. Furthermore, we use methods from optimal control to seek potential therapies for resetting the circadian clock, and maintaining clock amplitudes under environmental disruption.

Additional research in the Doyle group includes identifying biomarkers for posttraumatic stress disorder (PTSD) and the design of an artificial pancreas control system for treatment of type 1 diabetes. Ongoing work seeks to integrate these three projects, as PTSD is associated with poor circadian function, and insulin sensitivity and metabolic processes are modulated by sleep and the circadian clock.

Jeanne F. Duffy, MBA, PhD: Human circadian physiology; sleep and aging; individual differences in sleep timing, duration, and response to sleep loss. Her work has determined numerous factors influencing individual differences in sleep-wake timing, including aging, sex, and the trait of morningness-eveningness. Dr. Duffy began her career as a postdoctoral trainee in Dr. Czeisler’s laboratory

Monika Haack, PhD: Mechanisms involved in the relationship between sleep deficiency and pain, with a focus on stress and inflammatory systems markers as mechanistic candidates. Dr. Haack is testing pain and the stress system’s responses to sleep deficiency using highly controlled and lengthy in-laboratory models of experimentally induced sleep restriction and/or disruption in humans, as well as more naturalistic models, such as insomnia disorder. Dr. Haack began her career as a postdoctoral fellow with Dr. Janet Mullington.

Kun Hu, PhD: Circadian biology; fractal physiology; aging related disorders. Dr. Hu’s research aims to translate concepts of nonlinear dynamics to understanding of physiological and pathophysiological function. He finds altered fractal control in perturbed systems with aging and pathological conditions. Dr. Hu trained in the laboratory of Dr. Steven Shea when Dr. Shea was a preceptor on this training grant, and Dr. Saper was his co- mentor on his K01 award.

Hadine Joffe, MD's research focuses on the mechanisms underlying, consequences of, and treatment approaches to neuropsychological manifestations of female reproductive hormone changes in the brain (mood, sleep, and vasomotor symptom disturbance) in midlife women and breast cancer survivors. Her work involves experimental paradigms with use of both hormone- and sleep-manipulation to isolate the causal pathways linking hormonal changes and neural processes with vasomotor symptoms, sleep and mood disturbance, as well as the impact of reproductive transition physiology on metabolic and behavioral indices of body fat gain in women. She also conducts randomized trials to demonstrate the efficacy of therapies directed at vasomotor, sleep, and mood disturbance in midlife women and breast cancer survivors, as well as clinical and community-based epidemiologic studies of symptom burden in these populations.

Elizabeth B. Klerman, MD, PhD: Circadian rhythms, sleep, hormones, neurobehavioral performance and alertness and related mathematical analyses and modeling. Dr. Klerman is Team Lead of the Human Factors and Performance Team at NASA’s National Space Biomedical Research Institute. Dr. Klerman conducts both human experimental and mathematical modeling research. She has done experiments to understand mechanisms of homeostatic drive for sleep in older and younger individuals. Dr. Klerman began her career as a postdoctoral fellow in Dr. Czeisler’s laboratory.

Dara S. Manoach, PhD: Contribution of abnormal sleep to cognitive deficits in schizophrenia. Dr. Manoach’s projects incorporate electroencephalography, magnetoencephalography functional MRI and genetics to elucidate the links between deficient sleep-dependent memory consolidation and sleep spindles, identify effective treatments and identify genetic contributions. Dr. Manoach began her career as a postdoctoral fellow in Dr. Saper’s department where they collaborated on her early research on fMRI.

Janet Mullington, PhD: The effects of sleep loss on inflammation. Dr. Mullington investigates the role of sleep in host protection and has characterized the neuroendocrine, neuroimmune and EEG spectral qualities of sleep in response to varying doses of experimental bacterial challenge in healthy human subjects. She has found that C-reactive protein and IL-6, acute phase markers known to be predictive of future cardiovascular risk, are increased during sleep deprivation. They are currently investigating the contribution of age, autonomic and metabolic factors involved in these inflammatory changes.

Susan Redline, MD, MPH: Epidemiology/genetic epidemiology of sleep disorders; sleep and cardiovascular outcomes in adults and children. Dr. Redline has developed some of the largest sleep research databases in the world, directing the Sleep Reading Centers for most major NHLBI cohort studies (>50,000 research polysomnograms) and has helped develop novel informatics tools to enhance community wide access to these data. She also has led several seminal multicenter clinical trials of sleep apnea interventions. This work has identified the disproportionate prevalence of sleep apnea and insufficient sleep in children of low socioeconomic class and minority ethnicity; has defined the familial basis for sleep apnea and has identified a role for inflammatory and ventilatory control genes in sleep apnea; and has quantified the risk of hypertension, diabetes, stroke, heart failure, and mortality in association with sleep apnea and insufficient sleep. Dr. Redline is the Peter C. Farrell Professor of Sleep Medicine, served as a member of the IOM Committee that reported on Sleep Disorder: An Unrecognized Public Health Problem in 2006, and is an internationally recognized expert on sleep epidemiology. Dr. Redline trained in the Channing Laboratory here at BWH.

Clifford B. Saper, MD, PhD: Brain circuitry controlling sleep and circadian rhythms. Dr. Saper has defined the major arousal systems in the brain, and the neurons that turn those systems off to allow sleep to occur. He has also identified the pathways that allow transitions between rapid eye movement (REM) sleep and non- REM sleep, and those that transmit circadian signals from the suprachiasmatic nucleus to the wake-sleep system. Dr. Saper is the James Jackson Putnam Professor of Neurology, and Chairman of the Harvard Department of Neurology at the Beth Israel Deaconess Medical Center, and a member of the National Academy of Medicine. He is a Past President of the Sleep Research Society, and a fellow of the American Academy of Physicians, the American Association for the Advancement of Science, the American Neurological Association, the American Academy of Neurology, and the Royal College of Physicians (London). He is an internationally recognized sleep scientist, and the most highly cited scientist in the sleep field.

Thomas E. Scammell, MD: Neurobiology of narcolepsy and sleep. Dr. Scammell’s work demonstrated that orexin (hypocretin)-containing neurons of the hypothalamus are active during wakefulness and help stabilize wakefulness. Current research focuses on how the loss of orexin gives rise to the symptoms of narcolepsy. Dr. Scammell trained in the Saper lab. Dr. Scammell began his career as a postdoctoral trainee in Dr. Saper’s laboratory.

Frank A. J. L. Scheer, PhD’s research is primarily focused on medical chronobiology, including investigations of the underlying physiological mechanisms and therapeutic strategies to treat chronobiological disorders.  His work focuses on circadian and behavioral influences (including the sleep/wake cycle) on cardiovascular, pulmonary, and metabolic regulation and disease. Furthermore, he is interested in fundamental properties of the human circadian timing system, with work focusing on the effects of light. He has shown that endogenous melatonin production is important for sleep quality and that melatonin supplementation may be a logical therapy in certain patient populations. Furthermore, he has demonstrated that circadian misalignment, typical for shift work, leads to suppressed leptin, insulin resistance, and elevated blood pressure, providing possible physiological mechanisms to explain the increased risk for obesity, diabetes, and cardiovascular disease in shift workers.

Robert Strecker, PhD and colleagues have confirmed the role of adenosine as an endogenous sleep factor that mediates the sleepiness associated with prolonged wakefulness. These data indicate that adenosine acts as an inhibitory neuromodulator, inhibiting the wakefulness promoting neurons of the basal forebrain region. This work also provides a mechanism to understand the alertness promoting effects of caffeine and related compounds, since these agents are adenosine receptor antagonist.

Gianluca Tosini, PhD’s, research focuses on the role that melatonin signaling play in the regulation of retinal functions and on the role that the circadian clock play in the modulation of photoreceptors viability. Our studies have demonstrated that the action of melatonin on the photoreceptors is mediated by an MT1/MT2 heteromers and disfunction in melatonin signaling lead to photoreceptor cells degeneration during aging. Our laboratory has also shown that a functional circadian clock in the cone photoreceptors is important for the survival of these cell during aging.

Associate Preceptors

Laura Barger, PhD’s research focuses on the health and safety risks associated with the work hours of various occupational groups, including resident physicians, police officers, flight controllers, maritime bar pilots and federal air marshals.

Suzanne Bertisch, MD’s research focuses on the clinical impact of and mechanisms by which sleep disturbances impact cardiovascular (CV) risk and associated pain conditions, as well as behavioral interventions for sleep disturbance. My scientific contributions are summarized in four inter-related areas: 1) autonomic nervous system activity as a mediator of cardiovascular risk in patients with sleep disorders; 2) influence of sleep disturbances on pain; 3) role of sleep disturbances on populational CV outcomes; 4) novel behavioral sleep interventions that reduce sleep-related comorbidities. Additionally, Dr. Bertisch has been involved with several clinical innovations related to the delivery of OSA and insomnia care within the primary care setting.

Christopher Ehlen, PhD’s research is focused on investigating the role of sleep and sleep regulatory processes in resilience to stress-induced maladaptive behaviors

Takao K. Hensch, PhD: Critical periods in brain development, including the effects of sleep and sleep deprivation, which impacts not only the basic understanding of brain development, but also therapeutic approaches to devastating cognitive disorders later in life. Dr. Hensch helped to launch the RIKEN Brain Science Institute as lab head for Neuronal Circuit Development and served as Group Director for Critical Period Mechanisms Research (and now special advisor) before returning to the United States in 2006. Professor Hensch has received several honors, including the Young Investigator Award from the Society for Neuroscience both in Japan (2001 Tsukahara Prize) and the United States (2005), as well as an NIH Director’s Pioneer Award (2007). He currently directs the NIMH Silvio O. Conte Center for Basic Mental Health Research at Harvard.

Christopher P. Landrigan, MD, MPH: Effects of provider sleep deprivation on patient and provider safety. Dr. Landrigan studies the quality of the healthcare system (particularly in the inpatient setting) with a particular interest in the effects of provider sleep deprivation on patient and provider safety.

Jonathan Lipton, MD, PhD’s lab seeks to understand the fundamental relationships between the circadian clock and diseases of the developing brain. We have identified the core circadian clock protein BMAL1 as a regulator of protein synthesis (i.e. translation) (Cell, 2015). BMAL1 promotes circadian rhythms in protein synthesis as a substrate of the mechanistic target of rapamycin (mTOR) pathway, a critical gauge of nutritive status and stress. We have characterized a novel, potentially modifiable link between the circadian timing system and cellular signaling.

Kiran Maski, MD’s research is focused on a) identifying unique sleep symptoms and traits of pediatricneurological and neurodevelopmental disorders and b) determining the direct cognitive, behavioral, and psychological consequences of disrupted sleep and altered sleep architecture in children/adolescents. My career objective is to distill specific sleep diagnostic and prognostic biomarkers in neurological diseases and identify and test specific sleep treatments to reduce disease burden.

Michael Prerau, PhD’s lab’s research focuses on experimental and computational approaches to understanding the neural correlates of consciousness in humans—specifically how sleep affects the brain. We specialize in using the state-of-the-art in quantitative approaches to develop novel statistical signal processing algorithms for the analysis of neural data, with direct applications to basic science, biomarker discovery, and medical device development.

Tamar Sofer, PhD‘s lab  studies outcomes such as sleepiness, and cardiovascular outcomes. In combination with ‘omics markers, such as metabolites, we consider the metabolic environment induced by sleep states, and how this environment affects such outcomes, and modifies the way that genotypes related to these outcomes.  performance; and predicting how individuals will perform under different schedules and optimizing individuals’ performances.

Richa Saxena, PhD: Genetics of circadian rhythms/sleep disorders and their association with common diseases, such as type 2 diabetes. Dr. Saxena’s lab integrates genome-wide human genetic approaches with focused mechanistic investigation to understand how genetic variation in circadian clock genes impacts normal human physiology, disease pathophysiology and response to therapy.

Andrew Wellman, MD: Developing new therapies for sleep apnea through a better understanding of the pathophysiology. Dr. Wellman has RO1 funding to study the phenotype traits of OSA including upper airway anatomy/collapsibility, ventilatory control sensitivity, pharyngeal muscle responsiveness, and respiratory arousal threshold. Dr. Wellman began his career as a postdoctoral trainee in Drs. David White’s and Atul Malhotra’s laboratory when they were preceptors on this training grant.

John W. Winkelman, MD, PhD: Sleep-related movement disorders, insomnia, and parasomnias. His lab provided the first demonstration of a neurochemical abnormality in insomnia, as well as some of the first papers on the autonomic consequences of periodic leg movements of sleep (PLMS), the elevated risk of cardiovascular disease in RLS, and the elevated risk that RLS confers for mortality in patients with end stage renal disease (ESRD). Dr. Winkelman is available to advise trainees in the execution of clinical research studies and many MD fellows choose to perform a rotation in the sleep clinic.

Affiliate Preceptors

Maria Lehtinen, PhD: Research advances over the past decade have revealed diverse and unexpected roles for the cerebrospinal fluid (CSF).CSF comprises a vital, sophisticated and dynamic cocktail of growth factors and nutrients originating largely from the choroid plexus (ChP) epithelial sheet. ChP regulation of CSF likely involves selective transcytosis of blood-borne signals as well as de novo synthesis and secretion of signals by ChP epithelial cells. This same network of cells may also regulate clearance of toxins and waste and may control CSF production and clearance during different brain states including sleep. The unique functionality and location of ChP cells positions them to broadly impact neural excitability, plasticity, and health. However, compared to other vital organs, our understanding of the ChP-CSF system is in its infancy, in part due to the technical challenges inherent to studying a fluid deep inside the brain. With collaborators, we have applied a suite of modern tools to the ChP including transcriptomics and two-photon imaging in awake mice, providing a new opportunity to transform this historically understudied area of neuroscience into a robust field defining the roles of ChP and CSF throughout life. Our goal is to systematically study ChP biology across three focus areas: (1) diversity and division of labor among ChP cellular networks, (2) mechanisms regulating the synthesis and secretion of CSF including circadian contributions, and (3) ChP-CSF contributions to lifelong brain health. We envision a future where developmental and adult dysregulation of the CSF associated with neurologic diseases can be detected and corrected.

Stephen Liberles, PhD’s lab uses molecular and genetic approaches to study the vagus nerve; we (1) identified vagal receptors, (2) classified and genetically accessed sensory neuron subpopulations, and (3) adapted genetic approaches for anatomical mapping, in vivo imaging, targeted cell ablation, and remote control of vagal afferents. A major goal of our research program is to identify receptors important for internal organ sensation by the vagus nerve. Identifying vagal sensory receptors will advance the field of neurophysiology and may provide new ways to treat autonomic disease.

Yakeel Quiroz, PhD’s research interests focus on studying the neural underpinnings of memory dysfunction in the preclinical stages of Alzheimer’s disease (AD).  By applying her efforts to the world’s largest family with a single, early onset AD-causing mutation (E280A in PSEN1), her research has provided evidence of brain abnormalities in individuals at genetic risk for AD decades before their clinical onset. Her findings have helped the field to re-conceptualize Alzheimer’s as a sequence of changes that begins decades before cognitive decline, and which may be targeted by promising disease-slowing treatments at a time in which they might have their most profound effect.

Support Faculty

Stuart F. Quan, MD: Gerald E. McGinnis Professor of Sleep Medicine, Sleep Apnea Epidemiology in Adults and Children. Dr. Quan manages the Division educational activities such as the sleep and health education website. This educational tool provides a valuable resource for disseminating knowledge to the public and is also very useful tool for trainees who are interested in public outreach. Dr. Quan received an endowed chair to support these educational activities, which includes supporting our trainees in their early stages by providing senior mentorship and guidance.

Joseph M. Ronda, MS: Mr. Ronda is responsible for developing and supporting the use of computers as tools in medical research including the needs of trainees for data collection/analysis.

Wei Wang, PhD: Biostatistician, Brigham & Women’s Hospital and Lecturer on Medicine, Harvard Medical School. Dr. Wang is responsible for courses in statistical analysis related to trainees’ research, and she assists trainees in statistical design and interpretation of experiments.

David White, MD: Professor of Medicine, part time, Sleep Apnea Pathogenesis. He is available to our trainees on an ongoing basis and regularly interacts and provides guidance to trainees and young investigators interested in physiological and clinical research. He also is a resource regarding product development and innovation.

Administrative Support

Ms. Marisa Wooster: Project Coordinator of the Training Program. Ms. Wooster coordinates all training grant committee activities and data tabulation.

Ms. Carmen Varga: Administrator, Division of Sleep Medicine, Brigham & Women’s Hospital. Ms. Varga is responsible for the overall management and administration of the training grant.

Faculty Committees
Several faculty committees oversee this Training Program, including an Education and Training Committee consisting of all preceptors, and four standing sub-committees: Trainee Selection, Curriculum Development, Minority Recruitment and Tracking and Evaluation. For more information on committee structure and responsibilities, please visit the Faculty Committees of the Training Program page.

Updated on January 19th, 2022