CCHS Research

The CCHS Network is committed to investigational studies into the molecular mechanisms of CCHS, best clinical practices in CCHS, and best patient-centered outcomes research. The CCHS Network partners with CCHS Clinical Centers of Excellence, CCHS research laboratories, respiratory and pharmacological companies, and other CCHS patient organizations to champion research initiatives that will improve patient health outcomes. Learn more about our CCHS Grant Awards.

The CCHS Network relies on the CCHS Research Advisory Board to assess research quality. This board is comprised of CCHS family members who are medical professionals and CCHS clinical specialists. They apply an NIH criteria when judging research excellence.

The CCHS Foundation and the CCHS Research Advisory Board are both subsidiaries of the CCHS Network. Please visit our website at for more information.

CCHS Network One World (NOW) Registry

In the 2016 the CCHS Network was chosen, after a competitive selection process, to partner with the National Organization of Rare Disorders (NORD), to develop a Natural History Study of CCHS. The goal of this registry is to expand the current knowledge of the syndrome, as well as to aid medical professionals and researchers in the identification of important aspects and treatment of CCHS. Please contact the CCHS NOW Registry for more information about this work and how to join this important project.

2019 Research Projects of CCHS Network

Gene Regulation by Phox2b in Respiratory Chemoreceptor Neurons

Dr. Douglas A. Bayliss, Ph.D. is the Joseph and Frances Larner Professor & Chair of Pharmacology at the University of Virginia. Dr. Bayliss received his Ph.D. from the University of North Carolina, Chapel Hill.

Dr. Bayliss and team’s proposed  research utilizes single cell deep sequencing approaches, along with cell-specific gene manipulation, to characterize effects of Phox2b depletion/mutation on the unique gene expression profile of the respiratory chemoreceptor neurons in the retrotrapezoid nucleus (RTN), a group of brainstem neurons that has been implicated in CCHS. Our initial scRNA-Seq study, supported by CCHS Family Network, provided the first insights into the unique molecular genetics of this specific group of RTN neurons; the current application extends that previous work by examining how the RTN transcriptome is regulated by Phox2b.

Investigating degradation pathways of misfolded mutant PHOX2B in neurons derived from CCHS patient-specific iPSCs

Dr. Gad Vatine, Ph.D., researcher at Ben-Gurion University of the Negev, Department o Physiology and Cell Biology, Faculty of Health Sciences and The Regenerative Medicine and Stem Cell (RMSC) Research Center and Dr. Avraham Ashkenazi, Ph.D., Department of Cell and Developmental Biology at Tel-Aviv University are collaborating to investigate degradation pathways of misfolded PHOX2b proteins.

Drs. Vatine and Ashkenazi  propose to form an interdisciplinary
consortium consisting of two research groups in close collaboration with the Israeli CCHS patients’ advocacy organization. Mutant PHOX2B is prone to misfolding and aggregation, which seems to be correlated with toxic gain-of-function via yet unknown mechanisms. Autophagy and the
proteasome are key pathways of the proteostasis network that mediates the removal of misfolded proteins and promotes neuron survival. Consortium participants will work together to generate patient-specific derived disease-specific models, and to test mutant PHOX2B involvement in proteostasis defects. Better understanding of the mechanisms and pathways affected by the mutant protein and the CCHS patient-specific models generated in our project will consequently enable the development of state-of-the-art technologies and help to generate new effective therapeutic treatments.

Could Hypothalamic Deep Brain Stimulation Improve Breathing?

Dr. Ha Trang, MD, Ph.D. at the French Centre of reference of CCHS, Assistance Publique Hôpitaux de Paris, Hôpital Robert Debré,, Departmentt of Physiology and Dr. Brigitte Piallat, PhD, scientific PI at the Brain Stimulation & Systems Neuroscience unit at Grenoble Institute of Neuroscience are collaborating on this novel approach to better undertsand CCHS.

Drs. Trang and Piallat aim to determine if deep brain stimulation in the
hypothalamus could affect breathing, and if yes, which hypothalamic areas would be the most relevant potential targets in the treatment of central hypoventilation. In 2 non human primates, chronic electrodes will be implanted for measurement of neurological and respiratory parameters (respiratory rate, inspiratory time, PO2 and PCO2 values). If hypothalamic deep brain stimulation improves breathing, this technique may be considered as a new treatment option of central hypoventilation for patients with CCHS. Furthermore, mapping hypothalamic areas involved in control of breathing will open up large windows of research to unknown and/or even unexpected aspects of the tangled mechanisms of brain control of breathing.