Faculty Profile

Kun Hu, PhD

Kun Hu Profile 201802
Associate Professor of Medicine, Harvard Medical School
Associate Physiologist, Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital

Other Affiliation(s)

Director, Medical Biodynamics Program, Brigham and Women's  Hospital

See publications


Inter-office Mail Address

221 Longwood Avenue, 036 BLI

Phone 617-525-8694
Fax 617-732-7337

Email khu@bics.bwh.harvard.edu

Society Memberships

American Academy of Sleep Medicine
Sleep Research Society


Research Unit(s)

Medical Biodynamics Program, Division of Sleep Medicine, Brigham & Women's Hospital
Medical Chronobiology Program, Division of Sleep Medicine, Brigham & Women's Hospital
Sleep Disorders Research Program, Division of Sleep Medicine, Brigham & Women’s Hospital

Related Websites
Medical Biodynamics Program
Medical Chronobiology Program
Center for Dynamical Biomarkers and Translational Medicine (CDBTM)
Syncope and Falls in the Elderly (SAFE) Laboratory

Research Interests

Outputs of many physiological systems possess intriguing dynamic features such as fractal patterns — similar fluctuation structures at different time scales — that require nonlinear regulation at multiple time scales. These multiscale regulatory patterns are integrative behaviors of systems and cannot be understood by traditional deductive approaches in which one decomposes a system into its constituent pieces, studies each component, and then reassembles the components into the original entity. Concepts and methods derived from modern nonlinear dynamics are promising tools for the assessment of the complex multiscale regulation in physiology. Medical Biodynamics Program at Brigham & Women’s Hospital is established to promote such translational research in the field of sleep medicine and to facilitate the interdisciplinary collaborations of clinicians, biomedical researchers, physicists, applied mathematicians and engineers. The long-term goal is to address the challenge of connecting the changes on microscopic (e.g., molecular, cellular, and neuronal) levels to dynamics observed on the integrative organismic level. Achieving the goal is crucial for better understanding disease and aging processes in which pathologic perturbations on microscopic levels have dramatic impacts on adaptability and functionality on the macroscopic level.

Trainees

Undergraduate students
Lukas Lepicovsky, B.S. 2005
Thomas J Shea, B.S. 2009

PhD or medical students

April Alston, PhD 2006
Scott Pope, PhD 2007
Mareile Haertle, PhD 2007
Mikio Aoi, PhD 2009
Esther Martens, PhD 2010
Chien-Hung Yeh 2015-2016
Stefan Knapfen 2017-2018

Post-doctoral
Heli Valkeinen, PhD 2010
Bradley Manor, PhD 2008-2010
Men-Tzung Lo, PhD 2007-008
Benjamin Pittman-Polletta, PhD 2011- 2013
Wan-hsin Hsieh, PhD 2011- 2014
Wei-yin Chiagn, PhD 2011- 2014
Peng Li 2015-present
Lei Gao 2017-present

Mentor(s)

Steven A. Shea, PhD, 2005-present
Vera Novak, PhD, MD, 2005-2008
Clifford B Saper, PhD, MD, 2009-present

Research Funding

R01AG048108-01A1  Hu (PI)                    09/01/15-04/30/19
NIH/NIA           
Neuropathology for disrupted multiscale activity control in Alzheimer's disease
The goal of this project is to test whether multiscale activity control, a recently revealed novel dynamic control in motor activity fluctuations, can be used as a cost-efficient, reliable tool to predict cognitive decline and the risk of Alzheimer’s disease (AD) in elderly individuals.
Role: PI

2P01AG009975  Czeisler (PI)                08/01/13-07/31/18   
NIH/NIA
Sleep, Aging and Circadian Rhythm Disorders
The major goal of this project is to assess whether the role of the circadian system in the disturbed sleep is characteristic of elderly humans, and to determine the effect of aging upon the consequences of sleep restriction in terms of cognitive performance, vigilance and metabolic changes.
Role: Co-Investigator

Selected Completed Research Support (past 3 years)

R00HL102241  Hu (PI)                        04/01/12-03/31/16
R00HL102241-03        Hu (PI)    04/01/12-03/31/15
NIH/NHLBI
Fractal Regulatory Function of the Circadian System
This is the independent investigator phase of the Pathway to Independence Award Program (K99/R00). The aim of this career award is to facilitate PI’s research independence and to identify the neuronal nodes and pathways through which the circadian system imparts fractal activity control.
Role: PI

NSC 99-2911-I-008-100     Norden E Huang (PI)        12/01/10-11/30/15
National Science Council, Taiwan
Center for Dynamical Biomarkers and Translational Medicine   
The mission of the center is to establish a multidisciplinary team of clinicians, medical researchers, physicists, applied mathematicians, computer scientists and engineers in order to translate modern nonlinear dynamics approaches to medical research.
Role: Co-PI (responsible for the development of a training program with international collaboration that can foster young researchers with great potential in the new field of dynamical biomarkers for transitional medicine

NNX10AR10G        Stevenhea A Shear (PI)        10/01/10-09/30/14   
NASA                        
Identification of Cardiometabolic Vulnerabilities Caused by Effects of Synergistic Stressors that are commonly encountered during Space Missions
The major goal of this grant is to assess the cardiovascular responses to exercise, postural tilt and mental stress during combined sleep deprivation and circadian misalignment, as occurs with space flight.
Role: Co-investigator

Selected Publications

Yeh C, Lo M, Hu K. Spurious cross-frequency amplitude-amplitude coupling in nonstationary, nonlinear signals. Physica A 2016 Jul 15;454:143-150. PMID: 27103757; PMCID: PMC4834901.

Hu K, Riemersma-van der Lek RF, Patxot M, Li P, Shea SA, Scheer FA, Van Someren EJ. Progression of Dementia Assessed by Temporal Correlations of Physical Activity: Results From a 3.5-Year, Longitudinal Randomized Controlled Trial. Sci Rep. 2016 Jun 13;6:27742. doi: 10.1038/srep27742. PMID: 27292543; PMCID: PMC4904193.

Wang JL, Lim AS, Chiang WY, Hsieh WH, Lo MT, Schneider JA, Buchman AS, Bennett DA, Hu K, Saper CB. Suprachiasmatic neuron numbers and rest-activity circadian rhythms in older humans. Ann Neurol. 2015 Aug;78(2):317-22. PMID: 25921596; PMCID: PMC4515161.

Lo MT, Chang Y, Lin C, Young HV, Lin Y, Ho Y, Peng CK, Hu K. Outlier-resilient complexity analysis of heartbeat dynamics. Sci Rep. 2015 Mar 6;5:8836. doi: 10.1038/srep08836.
PMID: 25744292; PMCID: PMC4351527.

Hu K, Harper D, Shea SA, Stopa EG & Scheer FAJL. Noninvasive fractal biomarker of clock neurotransmitter disturbance in humans with dementia. Scientific Reports 3, 2229; DOI:10.1038/srep02229 (2013). PMID: 23863985. PMCID: PMC3714649.

Hu K, Lo MT, Peng CK, Liu Y, Novak V. A nonlinear dynamic approach reveals a long-term stroke effect on cerebral blood flow regulation at multiple time scales. PLoS Computation Biology 2012; 8(7), e1002601. PMCID: PMC3395609.

Aoi MC, Hu K, Lo MT, Selim M, Novak. Cerebral autoregulation is associated with brain atrophy and worse functional status in chronic ischemic stroke. PloS One 2012; 7(10), e46794. PMID: 23071639. PMCID: PMC3469603.

Scheer FA, Hu K, Evoniuk H, Kelly E, Malhotra A, Shea SA. Impact of the human circadian system, exercise, and their interaction on cardiovascular function. Proc Natl Acad Sci U S A. 2010; 107(47): 20541-46. PMID: 21059915. PMCID: PMC2996667.

Hu K, Lo MT, Peng CK, Novak V, Schmidt EA, Kumar A, Czosnyka M. Nonlinear pressure-flow relationship is able to detect asymmetry of brain blood circulation associated with midline shift. Journal of Neurotrauma. 2009;26(2):1-7. PMID: 19196074; PMCID: PMC2788024.

Lo MT, Novak V, Peng CK, Liu Y, Hu K. Assessment of nonlinear phase interaction between nonstationary signals: A comparison study of methods based on Hilbert-Huang and Fourier transforms. Phys Rev E. 2009; 79 (6) 061924. PMID:19658541; PMCID: PMC2730740.

Hu K, Van Someren EJW, Shea SA, Scheer FAJL. Reduction of scale-invariance of activity fluctuations with aging and Alzheimer’s disease: involvement of the circadian pacemaker. Proc Natl Acad Sci. 2009;106(8):2490-2494. PMID:19202078; PMCID: PMC2650290.

Hu K, Scheer FAJL, Buijs RM, Shea SA. The endogenous circadian pacemaker imparts a scale-invariant pattern of heart rate fluctuations across time scales spanning minutes to 24 hours. J Biol Rhythms. 2008;23(3):265-73. PMID: 18487418; PMCID: PMC2885843.

Hu K, Peng CK, Huang NE, Wu Z, Lipsitz LA, Cavallerano J, Novak V. Altered Phase Interactions between Spontaneous Blood Pressure and Flow Fluctuations in Type 2 Diabetes Mellitus: Nonlinear Assessment of Cerebral Autoregulation. Physica A. 2008;387(10):2279-2292.

Hu K, Scheer FAJL, Ivanov PCh, Buijs RM, Shea SA. The suprachiasmatic nucleus functions beyond circadian rhythm generation. Neuroscience. 2007;149:508-17. PMID: 17920204; PMCID: PMC2759975.

Ivanov PCh, Hu K*, Hilton MF, Shea SA, Stanley HE. Endogenous circadian rhythms in human motor activity uncoupled from circadian influences on cardiac dynamics. Proc Natl Acad Sci. 2007;104(52):20702-20707. PMID: 18093917; PMCID: PMC2410066. [* equal first author]

Chen Z, Hu K, Stanley HE, Novak V, Ivanov PCh. Cross-correlation of instantaneous phase increments in pressure-flow fluctuations: Applications to cerebral autoregulation. Phys Rev E. 2006;73:031915

Chen Z, Hu K, Carpena P, Bernaola-Galvan P, Stanley HE, Ivanov PCh. Effect of nonlinear filters on detrended fluctuation analysis. Physical Review E. 2005;71:011104. PMID: 15697577.

Chen Z, Ivanov PCh, Hu K, Stanley HE. Effect of nonstationarities on detrended fluctuation analysis. Physical Review E. 2002;65:041107. PMID: 12005806.

Hu K, Ivanov PCh, Chen Z, Carpena P, Stanley HE. Effect of trends on detrended fluctuation analysis. Physical Review E. 2001;64:011114. PMID: 11461232.

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